Pharmacotherapy [JOURNAL]
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200 papers
Aspirin Deprescribing Interventions for Primary Prevention: A Systematic Review and Proposed Guidance for Deprescribing.
Lobkovich A, Ferrari H, Martirosov AL … +4 more , Mohammad I, Berlie H, Garwood C, Lipari M
Pharmacotherapy · 2026 Mar · PMID 41709404 · Publisher ↗
Recent literature indicates that the benefits of aspirin use for primary prevention of atherosclerotic cardiovascular disease (ASCVD) may be equivocal to the risk. This has resulted in several organizations making update...
Recent literature indicates that the benefits of aspirin use for primary prevention of atherosclerotic cardiovascular disease (ASCVD) may be equivocal to the risk. This has resulted in several organizations making updates to their clinical practice guidance on appropriate use. Despite this narrower scope, specific guidance on how to deprescribe aspirin in patients already on therapy for primary prevention is lacking. The purpose of this paper is two-fold: to provide a systematic review of the literature on aspirin deprescribing strategies and propose a practical aspirin deprescribing algorithm when used discordantly with current recommendations for primary prevention. We conducted searches in databases including EMBASE, PubMed, Web of Science, Scopus, and CINAHL from January 2018 to March 2025. One hundred and sixty-seven studies were screened, and 13 articles were included. The studies utilized a variety of interventions to impact aspirin deprescribing. In each of the studies included, there was at least some type of prompt to trigger deprescribing aspirin. However, a consistent approach was not defined. A multidisciplinary model occurred in half of the studies included, which resulted in the highest reported deprescribing rate of 78%. However, there were limited descriptions of patient-related outcomes as a result of deprescribing, warranting additional studies. A deprescribing algorithm can assist in guiding aspirin deprescribing for primary prevention of ASCVD while considering patient preferences in an individually tailored approach.
Probiotic Supplementation as an Adjuvant Therapy in Pediatric Drug-Resistant Epilepsy: A Double-Blind Placebo-Controlled Trial.
Rashdan AR, El-Haggar SM, Kishk AM … +1 more , Mostafa TM
Pharmacotherapy · 2026 Mar · PMID 41693686 · Publisher ↗
BACKGROUND: Drug-resistant epilepsy (DRE) is increasingly linked to neuroinflammatory mechanisms driven by gut dysbiosis. These mechanisms compromise blood-brain barrier integrity, enhance seizure susceptibility, and mod...
BACKGROUND: Drug-resistant epilepsy (DRE) is increasingly linked to neuroinflammatory mechanisms driven by gut dysbiosis. These mechanisms compromise blood-brain barrier integrity, enhance seizure susceptibility, and modulate immune pathways. These insights underscore the therapeutic potential of microbiota-targeted interventions in epilepsy. AIM: The study aimed at assessing the effectiveness of probiotics as an adjunctive therapy to enhance drug sensitivity and clinical outcomes in children with DRE. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 60 pediatric patients with DRE who were assigned to either the control group (n = 30), which received a standard antiepileptic regimen (valproic acid, oxcarbazepine, and levetiracetam at the maximum tolerated doses) plus a daily placebo capsule, or the probiotic group (n = 30), which received the same antiepileptic regimen plus a daily probiotic (Lactobacillus acidophilus) supplement. The study duration was 6 months. Assessments of clinical and biochemical outcomes were conducted at baseline and 6 months after intervention. Primary end points included seizure frequency and change in quality of life as measured by the quality of life in childhood epilepsy (QOLCE-55) questionnaire. Secondary end points included the change in the serum levels of high-mobility group box 1 protein (HMGB1), interleukin-1β (IL-1β), homocysteine (Hcy), and NLR family pyrin domain-containing 3 (NLRP3). RESULTS: After 6 months and relative to the control group, the probiotic (Lactobacillus acidophilus) group experienced a significant decline in seizure frequency (p = 0.04) and a significant improvement in the QOLCE-55 total score (p < 0.0001). Additionally, the probiotic group exhibited significant decreases in the serum levels of HMGB1 (p = 0.0005), NLRP3 (p = 0.002), Hcy (p = 0.001), and IL-1β (p = 0.05) compared with the control group. CONCLUSION: Lactobacillus acidophilus supplementation appears to enhance the effectiveness of conventional antiepileptic drugs, reduce systemic inflammation, improve quality of life, and reduce seizure frequency in children with DRE. However, further validation is necessary. GOV REGISTRATION NUMBER: NCT05539287.
Current and Emerging Pharmacologic Therapies for Diabetic Retinopathy.
Clements JN, Mesawich J, Twisdale C
Pharmacotherapy · 2026 Mar · PMID 41693076 · Full text
Diabetic retinopathy, a prevalent microvascular complication of diabetes mellitus, is a leading cause of blindness among adults in developed countries. Risk factors include prolonged duration of diabetes, elevated glycos...
Diabetic retinopathy, a prevalent microvascular complication of diabetes mellitus, is a leading cause of blindness among adults in developed countries. Risk factors include prolonged duration of diabetes, elevated glycosylated hemoglobin levels, hypertension, and dyslipidemia, with rapid glucose reduction also increasing risk for developing diabetic retinopathy. The American Academy of Ophthalmology classifies diabetic retinopathy into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy, distinguished by the absence or presence of neovascularization, respectively. Complications such as diabetic macular edema, retinal detachment, and irreversible vision loss further underscore the need for effective therapies. Current treatments include laser photocoagulation, vitrectomy, and anti-vascular endothelial growth factor agents. This narrative review evaluates established pharmacotherapy and explores emerging therapies targeting novel pathways such as inflammation, oxidative stress, and vascular stability. Investigational agents, including integrin inhibitors, gene therapies, and small-molecule antagonists, alongside innovative delivery systems such as topical formulations and sustained-release implants, offer the potential to enhance treatment efficacy, patient adherence, and overall outcomes in diabetic retinopathy. By examining these advancements, including innovative delivery systems, this review aims to inform practitioners about the evolving landscape of pharmacotherapy for diabetic retinopathy.
Oral β-Lactams for Complicated Urinary Tract Infections: A Systematic Review and Point-Counterpoint Comparison With Trimethoprim/Sulfamethoxazole and Fluoroquinolones.
Kunz Coyne AJ, Bouchard J, Durham SH … +10 more , Kang AY, Johannemann KM, Moore WJ, Nguyen K, Sanders J, Sheveland C, Stimes G, Trinh T, Covington EW, ACCP Infectious Disease Practice and Research Network (PRN) Research Committee
Pharmacotherapy · 2026 Mar · PMID 41693075 · Publisher ↗
BACKGROUND: Rising resistance and toxicity concerns with fluoroquinolones (FQs) and trimethoprim/sulfamethoxazole (TMP/SMX) have prompted interest in oral β-lactams as alternatives for complicated urinary tract infection...
BACKGROUND: Rising resistance and toxicity concerns with fluoroquinolones (FQs) and trimethoprim/sulfamethoxazole (TMP/SMX) have prompted interest in oral β-lactams as alternatives for complicated urinary tract infections (cUTIs). This review evaluates the effectiveness, safety, and pharmacokinetic (PK) considerations of oral β-lactams compared to FQs and TMP/SMX in these clinical contexts. A structured point-counterpoint discussion explores their role in antimicrobial stewardship and patient-centered therapy. METHODS: A systematic PubMed search identified studies published between January 2000 and December 2025. Eligible studies included randomized trials and observational cohort studies evaluating clinical effectiveness, microbiological outcomes, or safety of oral β-lactams for cUTIs or bacteremic UTI compared with FQs or TMP/SMX. Outcomes of interest included treatment success, recurrence, adverse events, and PK considerations. Excluded studies involved special populations, nontraditional agents, or infections outside the scope of cUTI. Data were synthesized narratively due to heterogeneity in study design and outcome reporting. RESULTS: Seventeen observational studies met the inclusion criteria. Oral β-lactams demonstrated comparable effectiveness to FQs and TMP/SMX for cUTIs, including bacteremic UTI, when dosed appropriately. Oral β-lactams with high oral bioavailability (e.g., cephalexin, cefpodoxime, cefuroxime, amoxicillin/clavulanate), showed success rates exceeding 90%, but recurrence was higher when underdosed. Oral β-lactams had lower adverse event rates (1.3%) compared to FQs (2.3%) and TMP/SMX (5.7%), but may carry limitations including frequent dosing, variable bioavailability, and susceptibility testing challenges. CONCLUSIONS: Although not traditionally recognized as first-line therapy, select oral β-lactams demonstrated effectiveness comparable to FQs or TMP/SMX for cUTIs and bacteremic UTI and can serve as effective alternatives in appropriately selected patients. When optimally dosed, these β-lactams achieve comparable outcomes with favorable safety profiles and antimicrobial stewardship advantages. Randomized trials are needed to confirm these observational findings and to better define optimal dosing strategies and shorter treatment durations.
Cohort Study to Determine the Impact of CYP3A5 Genotype on Tacrolimus Dosing Requirements and Trough Concentrations in Heart Transplant Recipients.
Wu Y, Eadon MT, Schenkelberg L … +4 more , Rao RA, Skaar TC, Tillman EM, Shugg T
Pharmacotherapy · 2026 Mar · PMID 41660740 · Full text
BACKGROUND: Tacrolimus is primarily metabolized by Cytochrome P450 (CYP)3A4/5. The Clinical Pharmacogenetics Implementation Consortium recommends increasing the initial dose 1.5- to 2-fold in CYP3A5 expressers to enhance...
BACKGROUND: Tacrolimus is primarily metabolized by Cytochrome P450 (CYP)3A4/5. The Clinical Pharmacogenetics Implementation Consortium recommends increasing the initial dose 1.5- to 2-fold in CYP3A5 expressers to enhance transplant outcomes. Our objective was to investigate the impact of CYP3A5 expresser status on tacrolimus dosing requirements and attainment of target trough concentrations in heart transplant recipients. METHODS: We performed a retrospective cohort analysis of tacrolimus dose, concentration, demographics, CYP3A4/5 genotype, concomitant medications, and biochemical data in heart transplant recipients from December 2020 to August 2023. The primary outcome was the time to first therapeutic trough concentration, compared by CYP3A5 expression status. Secondary outcomes included the tacrolimus dose at target trough and dose-adjusted tacrolimus trough concentration (C/D). Stepwise multiple regression was performed to account for potential covariates. Moreover, clinical outcomes were assessed at 1-year post-transplantation and compared based on CYP3A5 expression status. RESULTS: Among 33 patients, CYP3A5 expressers (27.3%) required longer to achieve therapeutic trough concentrations (median [Q1, Q3]: expressers: 14 [9.5, 16] days vs. nonexpressers 7.5 [6.0, 11] days; p = 0.0073) and required nearly double the tacrolimus dose to reach target concentrations (10 [5.5, 13] mg/day for expressers vs. 5 [3.3, 5.9] mg/day for nonexpressers; p = 0.0019). Conversely, the C/D was nearly 2-fold higher in nonexpressers 2.0 [1.6, 3.4] ng/(mL*mg) than expressers (1.1 [0.83, 1.7] ng/(mL*mg); p = 0.0015). Stepwise regression identified route of administration (sublingual vs. oral) at therapeutic trough and initial dose as covariates for all outcomes. All clinical outcomes showed no significant differences based on CYP3A5 expression status, with the exception that poor metabolizers demonstrated higher serum creatinine elevation at 1-week post-transplantation (p = 0.047). CONCLUSION: Our findings highlight the impact of CYP3A5 expresser status on the time needed and dosing requirements to attain tacrolimus therapeutic concentrations in heart transplant recipients, suggesting CYP3A5-guided dosing strategies may improve rapid attainment of therapeutic tacrolimus concentrations.
Considerations for Menstrual Suppression in Patients With Hematologic Malignancies.
Veeravalli S, Schepers A, Benitez LL … +1 more , Fraga MS
Pharmacotherapy · 2026 Mar · PMID 41660710 · Full text
Patients who menstruate during treatment for hematologic malignancies have a higher risk of heavy vaginal bleeding due to thrombocytopenia caused by malignancy and myelosuppressive chemotherapy. Heavy menstrual bleeding...
Patients who menstruate during treatment for hematologic malignancies have a higher risk of heavy vaginal bleeding due to thrombocytopenia caused by malignancy and myelosuppressive chemotherapy. Heavy menstrual bleeding is associated with significant morbidity in this patient population, and menstrual suppression is a standard of supportive care. Options for prophylactic menstrual suppression include gonadotropin-releasing hormone agonists, progestin-only therapy, and combined hormonal contraception. Various factors impact the choice of menstrual suppression agent, including efficacy, presence of emergent acute uterine bleeding, desire for contraception, and presence of thrombotic risk factors. The purpose of this review is to discuss the nuances of available menstrual suppression agents in patients with hematologic malignancies and develop a methodical approach to consider patient-specific factors that impact agent selection.
Immune Checkpoint Inhibitor Exposure During Pregnancy: A Systematic Review.
Keller CL, Hermanson KC, Schuller RM … +1 more , Alzghari SK
Pharmacotherapy · 2026 Mar · PMID 41660707 · Publisher ↗
Immune checkpoint inhibitors (ICIs) have been widely implemented in current oncology practice. However, there is limited data regarding ICI administration in pregnancy. This systematic review aims to evaluate the risk-be...
Immune checkpoint inhibitors (ICIs) have been widely implemented in current oncology practice. However, there is limited data regarding ICI administration in pregnancy. This systematic review aims to evaluate the risk-benefit of ICI exposure in pregnant women. We conducted searches in databases including PubMed, Scopus, Web of Science, and Embase from January 1, 2011 through April 30, 2025. Included studies were those that involved women with a cancer diagnosis who received ICI treatment while pregnant and had clinical findings of the fetus post-ICI treatment. Methodological quality and potential sources of bias were assessed using Joanna Briggs Institute Critical Appraisal Tools. The search generated 2539 citations. After removal of 696 duplicates, a total of 1843 citations were screened. Twenty case reports and three retrospective studies were included in the systematic review. Fetal complications and fetal immune-related adverse events among the case reports were at 23% and 11.5%, respectively. Preterm delivery occurred in 54% of case reports, and no fetal mortalities were reported. Regarding the observational studies, preterm delivery occurred in 20.9%-25.5% of cases, fetal mortality occurred in 2.2%-15.3% of cases, intrauterine growth restriction occurred in 6.5%-7.1% of cases, and complications attributable to prematurity were reported in 2.6%-5.5% of cases. The data from this systematic review suggests that the risk for fetal complications may be lower than previously reported. As ICIs continue to expand their role in the treatment of malignancy, their use in pregnancy is more likely to come into clinical question. Clinicians should approach ICI use in pregnancy with individualized, multi-disciplinary risk-benefit discussions.
Development and Validation of a Time-Dependent Nomogram for Predicting Hematological Toxicity Risk During Linezolid Therapy in Drug-Resistant Tuberculosis.
Zhou W, Zhu H, Liu Z … +7 more , Nie W, Wang Q, Shi W, Yang Y, Qi W, Lu Y, Chu N
Pharmacotherapy · 2026 Mar · PMID 41660689 · Publisher ↗
BACKGROUND: Linezolid is essential for drug-resistant tuberculosis (DR-TB) treatment but causes frequent hematological toxicity. We developed a time-dependent nomogram to predict this risk. METHODS: A prospective cohort...
BACKGROUND: Linezolid is essential for drug-resistant tuberculosis (DR-TB) treatment but causes frequent hematological toxicity. We developed a time-dependent nomogram to predict this risk. METHODS: A prospective cohort of 201 patients with DR-TB receiving linezolid (600 mg/day) was enrolled. Blood trough concentration (C) and clinical variables were measured. Multivariable Cox regression identified predictors, with a nomogram constructed to estimate toxicity probability at 1, 3, and 6 months. Model performance was assessed via calibration curves, C-index, and time-dependent area under the curve (AUC). RESULTS: Ninety-six patients (47.8%) developed hematological adverse events (anemia: 26.4%, leukopenia: 14.4%, thrombocytopenia: 7.0%). Five predictors were significant: C > 2.08 mg/L [Hazard Ratio (HR) = 2.87, p < 0.001]; lower baseline white blood cells (HR = 0.84, p = 0.003), hemoglobin (HR = 0.99, p = 0.033), and creatinine clearance rate (HR = 0.99, p = 0.001); and initial treatment (HR = 0.56 vs. retreatment, p = 0.011). The nomogram showed good discrimination (C-index = 0.73) and calibration. Time-dependent AUCs were 0.74 (1-month), 0.79 (3-month), and 0.80 (6-month). Internal validation via bootstrapping (1000×) confirmed robustness. CONCLUSIONS: This nomogram, integrating C with baseline clinical factors, enables early identification of patients with DR-TB at high risk for hematotoxicity and could guide pre-emptive interventions. However, external validation is required to confirm its generalizability before widespread clinical implementation.
Association of Serotonin Transporter Gene 5HTTLPR rs25531 Polymorphism With Escitalopram Efficacy in Patients With Major Depressive Disorder.
Afridi MF, Zakki SA, Rafiullah R … +1 more , Haq IU
Pharmacotherapy · 2026 Feb · PMID 41606417 · Publisher ↗
BACKGROUND: Escitalopram is considered a cornerstone therapy for major depression, but inter-individual variations exist in its clinical efficacy. The current study aims to explore the possible association between seroto...
BACKGROUND: Escitalopram is considered a cornerstone therapy for major depression, but inter-individual variations exist in its clinical efficacy. The current study aims to explore the possible association between serotonin transporter gene (SLC6A4) polymorphism 5HTTLPR-rs25531 and clinical efficacy of escitalopram in a Pakistani population suffering from major depressive disorder. METHODOLOGY: This prospective observational analytical study was conducted from April 2023 to October 2024 in tertiary care hospitals. Four hundred and thirty depressive patients were recruited through non-probability purposive sampling. Patients were treated with escitalopram 10 mg once daily for 12 weeks. Patients were enrolled based on Hamilton Depression Rating Scale score of less than or equal to 20. Patients with a minimum 50% reduction in score at 12 weeks were designated as responders. Genotyping of 5-HTTLPR- rs25531 was performed by allele-specific polymerase chain reaction. RESULTS: Responders and non-responders of escitalopram therapy were 217 (50.50%) and 213 (49.5%) patients, respectively. Frequencies of LL, LS, and SS genotypes of HTTLPR polymorphisms were 19%, 47%, and 34%, respectively, and frequencies of L and S alleles were 0.43 and 0.57, respectively. A higher percentage reduction in the Hamilton Depression Rating Scale was observed in patients carrying LL (60.05% ± 21.24%) and LS (53.63% ± 22.8%) genotypes compared to those having the SS genotype (32.22% ± 16.59%). CONCLUSION: 5HTTLPR and rs-25,531 polymorphisms significantly influenced escitalopram efficacy, and patients carrying LL genotypes with LL haplotype and 2 L functional group have better treatment response to escitalopram therapy compared to other groups.
Cancer Therapy-Induced Cardiotoxicity: A Narrative Review.
Wells DA, Halford Z, Holman K … +1 more , Marjoncu D
Pharmacotherapy · 2026 Feb · PMID 41606414 · Publisher ↗
Cancer therapy-induced cardiotoxicity (CTIC) is a significant clinical challenge in an era of rapidly evolving oncologic treatment. This comprehensive narrative review synthesizes evidence from clinical trials, meta-anal...
Cancer therapy-induced cardiotoxicity (CTIC) is a significant clinical challenge in an era of rapidly evolving oncologic treatment. This comprehensive narrative review synthesizes evidence from clinical trials, meta-analyses, and guidelines to examine the definitions, mechanisms, offending agents, and preventative strategies for CTIC. Numerous therapeutic agents, beyond traditional chemotherapy, pose significant risks for cardiovascular events such as arrhythmias, hypertension, myocardial dysfunction, and vascular complications. These varied toxicity profiles necessitate individualized monitoring strategies. Given the rising cancer incidence and the proliferation of novel oral chemotherapeutic agents taken at home, non-oncology practitioners are increasingly likely to encounter patients with these cardiotoxicities. This creates a critical need for broader clinical familiarity with CTIC mechanisms and cardiovascular optimization strategies to mitigate long-term morbidity. Although existing evidence helps guide risk stratification, significant questions remain. Robust data from dedicated cardio-oncology trials, coupled with enhanced multidisciplinary collaboration, are urgently needed to define optimal prevention and treatment of CTIC for patients experiencing these serious adverse effects.
Development and Validation of a Novel Scoring Model Integrating Clinical Risk Factors and Pharmacokinetic Parameters to Predict Vancomycin-Induced Nephrotoxicity.
Matsuki Y, Sako KI, Kozima Y … +4 more , Watanabe T, Kashiwagura Y, Yasuno N, Watanabe S
Pharmacotherapy · 2026 Feb · PMID 41605883 · Full text
BACKGROUND: Vancomycin (VCM), a first-line treatment option for infections caused by methicillin-resistant Staphylococcus aureus, has been reported to cause nephrotoxicity even within therapeutic concentration ranges. Tr...
BACKGROUND: Vancomycin (VCM), a first-line treatment option for infections caused by methicillin-resistant Staphylococcus aureus, has been reported to cause nephrotoxicity even within therapeutic concentration ranges. Traditional therapeutic drug monitoring strategies rely primarily on the area under the concentration-time curve (AUC), without adequately accounting for multiple clinical risk factors associated with nephrotoxicity. OBJECTIVE: The present study aimed to develop a novel scoring model that integrates clinical risk factors and pharmacokinetic parameters to predict VCM-induced nephrotoxicity and validate its predictive performance. METHODS: We conducted a single-center retrospective cohort study on patients who received VCM therapy between April 2021 and March 2023. A multivariable logistic regression analysis was performed to identify independent risk factors for VCM-induced nephrotoxicity, and regression coefficients were used to construct the scoring model. The predictive performance of the proposed model was compared with a conventional AUC-based model using the area under the receiver operating characteristic curve (ROC AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: The scoring model consisted of the following components: the steady-state area under the concentration-time curve (0-8 points), the concomitant use of tazobactam/piperacillin (2 points), the use of loop diuretics (1 point), and the presence of chronic liver disease (2 points). The proposed model demonstrated high predictive performance, with ROC AUC values of 0.79 (95% confidence interval [CI]: 0.71-0.87) in the derivation cohort and 0.84 (95% CI: 0.72-0.96) in the validation cohort. Furthermore, the proposed model showed significantly better performance than the conventional model in terms of NRI (derivation cohort: 0.78, 95% CI: 0.47-1.08; validation cohort: 1.23, 95% CI: 0.79-1.67) and IDI (derivation cohort: 0.07, 95% CI: 0.04-0.11; validation cohort: 0.27, 95% CI: 0.15-0.39) (p < 0.001). CONCLUSION: The scoring model developed in the present study may enhance risk stratification for VCM-induced nephrotoxicity and contribute to advances in individualized dosing strategies in clinical practice.
Utilization of dd-cfDNA Monitoring to Facilitate Immunosuppression Minimization After Kidney Transplantation in a U.S. Veteran Population.
Cotiguala L, Przybylski A, Joyce C … +3 more , Hansen G, Shah N, Lopez-Soler RI
Pharmacotherapy · 2026 Jan · PMID 41568414 · Publisher ↗
BACKGROUND: Although donor-derived cell-free DNA (dd-cfDNA) serves as a monitoring tool for rejection, few studies have examined its utility in guiding immunosuppression management. Here, we present the largest kidney tr...
BACKGROUND: Although donor-derived cell-free DNA (dd-cfDNA) serves as a monitoring tool for rejection, few studies have examined its utility in guiding immunosuppression management. Here, we present the largest kidney transplant population in which immunosuppression minimization and subsequent surveillance were guided by dd-cfDNA. METHODS: This retrospective case series evaluated our immunosuppression minimization practice to tacrolimus and prednisone in kidney transplant recipients (KTR) from November 20, 2020, to September 26, 2024. Baseline dd-cfDNA ≤ 0.5% was required before minimization. Immune tolerance was defined by the absence of any immune event after minimization: absolute dd-cfDNA > 0.5%, relative change value (RCV) > 60% from baseline, biopsy-proven acute rejection (BPAR), or de novo donor-specific antibody (DSA). All other KTR were labeled intolerant. The primary endpoint was the rate of immune tolerance. RESULTS: Immunosuppression was modified to tacrolimus and prednisone in 38 KTR at a median of 223 days post-transplant. Most KTR were older adults at low immunological risk: mean of 69 years and all had a calculated panel reactive antibody of 0%. 21 (55.3%) KTR met the primary end point of tolerance. The remaining 17 KTR were labeled intolerant secondary to dd-cfDNA elevations including absolute > 0.5% or RCV > 60% (n = 16 of 17, 94%), de novo DSA (n = 2 of 17, 11.8%), and/or BPAR (n = 4 of 17, 23.5%). Although not statistically significant, intolerant KTR were numerically more likely to have 5-6 HLA mismatches (82.5% vs. 52.4%, p = 0.31), less likely to have thymoglobulin induction (29.4% vs. 42.9%, p = 0.39), and were minimized earlier after transplant (196 vs. 256 days, p = 0.08) compared with tolerant KTR, respectively. Intervention after dd-cfDNA elevations included immunosuppression increase (50%), additional dd-cfDNA monitoring (81.3%), DSA testing (50%), and allograft biopsy (18.7%). CONCLUSION: Approximately 50% of low immunological risk KTR with a baseline dd-cfDNA < 0.5% tolerated immunosuppression minimization to tacrolimus and prednisone without concerning dd-cfDNA elevations, BPAR, or DSA. Our study highlights the role of dd-cfDNA as part of the armamentarium for identifying minimization candidates and performing subsequent surveillance.
Safety of Tenecteplase in Stroke Mimics Compared With Acute Ischemic Stroke: A Retrospective Cohort Study.
Rowe AS, Wiseman B, Hamilton LA … +3 more , Crowell S, McCampbell L, Ford D
Pharmacotherapy · 2026 Jan · PMID 41567081 · Publisher ↗
BACKGROUND: Acute ischemic stroke (AIS) accounts for 87% of all strokes and is associated with high morbidity and mortality. Stroke mimics, conditions that present with stroke-like symptoms but are not AIS, represent an...
BACKGROUND: Acute ischemic stroke (AIS) accounts for 87% of all strokes and is associated with high morbidity and mortality. Stroke mimics, conditions that present with stroke-like symptoms but are not AIS, represent an important proportion of stroke cases. Tenecteplase, an alteplase variant with higher fibrin affinity and a longer half-life, has recently gained approval for the treatment of AIS. Limited evidence exists on the safety of tenecteplase in stroke mimics. OBJECTIVE: The objective of this study was to determine the incidence of intracranial hemorrhage in patients with stroke-like signs and symptoms who received tenecteplase with and without a confirmed diagnosis of AIS. METHODS: This was a single-center, retrospective cohort study conducted at a comprehensive stroke center. Patients who received tenecteplase for stroke-like symptoms from June 2020 to December 2021 were included. Patients were grouped based on AIS diagnosis confirmed by neuroimaging or discharge diagnosis. The primary outcome was the incidence of intracranial hemorrhage, and secondary outcomes included incidence of symptomatic and asymptomatic intracranial hemorrhage, extracranial hemorrhage, hospital length of stay, angioedema development, and discharge disposition. RESULTS: Of 250 patients, 174 were diagnosed with AIS and 76 with stroke mimics. Patients with AIS were older (69 years [SD: 13.8 years] vs. 62.3 years [SD: 16.1 years]; p = 0.0008), had higher hypertension prevalence (132 [75.9%] vs. 44 [57.9%]; p = 0.0042), and lower previous stroke prevalence (9 [5.2%] vs. 11 [14.5%]; p = 0.0126) compared with stroke-mimic patients, respectively. Patients with AIS had shorter median tenecteplase door-to-needle times (38.5 min [IQR: 30 min, 53 min] vs. 46.5 min [IQR: 34.5 min, 64.5 min]; p = 0.0154) compared with stroke mimics. Intracranial hemorrhage occurred in 11.5% of patients with AIS and none in stroke mimics (p = 0.0021). Symptomatic hemorrhage rates were similar between groups. Patients with AIS had longer median hospital stays (3 days [IQR: 2 days, 6 days] vs. 2 days [IQR: 2 days, 4 days]; p = 0.0018). Discharge dispositions and cases of angioedema were similar between groups. CONCLUSION: Tenecteplase appears safe for stroke mimics, with no disproportionate harm compared to patients with AIS. This study further supports the safety of tenecteplase in stroke mimics, aiding rapid treatment decisions in stroke-like presentations.
Comment on "Acute Pharmacodynamic Effects of Oral Levodopa on Blood Pressure in Parkinson's Disease".
Bouhaddi M, Vuiller F, Regnard J
Pharmacotherapy · 2026 Jan · PMID 41548212 · Publisher ↗
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Response to Comment on "Acute Pharmacodynamic Effects of Oral Levodopa on Blood Pressure in Parkinson's Disease".
Longardner K, Liu C, Momper JD … +5 more , Mahato K, Moonla C, Ghodsi H, Wang J, Litvan I
Pharmacotherapy · 2026 Jan · PMID 41548208 · Publisher ↗
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Association of an Algorithm-Generated Medication Optimization Score With Clinical Outcomes in Ambulatory Patients With Heart Failure.
Ali MS, Greer KM, Ganai S … +3 more , Koelling TM, Hummel SL, Dorsch MP
Pharmacotherapy · 2026 Jan · PMID 41548207 · Full text
AIMS: Guideline-directed medical therapy (GDMT) implementation in heart failure with reduced ejection fraction (HFrEF) remains suboptimal. A computable algorithm was developed to generate a medication optimization score...
AIMS: Guideline-directed medical therapy (GDMT) implementation in heart failure with reduced ejection fraction (HFrEF) remains suboptimal. A computable algorithm was developed to generate a medication optimization score (MOS) and provide guideline-based recommendations. This computable algorithm was previously validated using clinical trial data, and an updated version was developed in 2021 to include sodium-glucose co-transporter 2 inhibitors. This study evaluated the association between the medication optimization information generated by this version of the algorithm and clinical outcomes using real-world data. METHODS: We conducted a retrospective cohort study of 1352 ambulatory adult patients with chronic HFrEF who received care from the advanced heart failure service at the University of Michigan between July 1, 2021, and October 14, 2024. The algorithm-generated MOS was calculated using electronic health record data. The primary outcome was a composite of all-cause mortality or hospitalization. Cox proportional hazards models were used to evaluate the association between baseline MOS and the primary outcome. A time-varying Cox model using the running cumulative MOS and a marginal structural model (MSM) was also conducted. A linear mixed-effects model was used to assess improvement in MOS over time as the secondary outcome. RESULTS: In the analysis adjusted for HF severity and comorbidities, baseline MOS was associated with a lower hazard of the composite outcome (hazard ratio (HR) 0.96, 95% confidence interval (95% CI): 0.92, 0.99, p = 0.040). In the cumulative time-varying Cox model and the marginal structural model, the association with time-varying MOS became stronger, with HRs of 0.88 (95% CI 0.81-0.95; p = 0.0015) and 0.88 (95% CI 0.83-0.93; p < 0.001), respectively. The event rates per 100 person-years were 44.1 in MOS 0%-33%, 39.5 in MOS 34%-66%, and 31.8 in MOS 67%-100%. Longitudinally, MOS improved over time. CONCLUSION: Higher algorithm-generated MOS values were significantly associated with lower all-cause mortality or hospitalization, and the MOS values increased over the follow-up period. This suggested that this algorithm effectively identifies opportunities for GDMT optimization in real-world clinical settings.
Pharmacotherapeutic Controversies During Temperature Control After Out-of-Hospital Cardiac Arrest: A Semi-Structured Literature Review.
Forehand CC, Benken ST, Madorsky M … +15 more , Mohamed A, Nguyễn JV, Dixit D, Gallagher J, Hawkins WA, Heavner MS, Johnson E, Lozano L, Sisco M, Slampak-Cindric AA, Smith SE, Spezzano K, Taylor BA, Wayne NB, Gagnon DJ
Pharmacotherapy · 2026 Jan · PMID 41543891 · Full text
Post-resuscitation cardiac arrest care begins at the time of hospital admission and focuses on preventing the sequelae of ischemia-reperfusion injury, including secondary brain damage and post-cardiac arrest syndrome. Cl...
Post-resuscitation cardiac arrest care begins at the time of hospital admission and focuses on preventing the sequelae of ischemia-reperfusion injury, including secondary brain damage and post-cardiac arrest syndrome. Clinical practice guidelines on post-resuscitation cardiac arrest care from international medical organizations outline evidence-based practices but sometimes lack pragmatic details needed by bedside clinicians to implement change. Lack of information has required providers to extrapolate from other patient populations with acute brain injuries or utilize lower quality data from patient registries or observational studies. We organized a group of content experts to address selected pharmacotherapeutic controversies encountered during temperature control after out-of-hospital cardiac arrest in adult patients. Data on pre-hospital interventions, in-hospital cardiac arrest, and most non-pharmacologic treatments were excluded. A Delphi process was completed using three rounds of voting to reach consensus on pharmacotherapeutic controversies to review. The original list of 11 topics was narrowed iteratively and the final list included: (i) sedation and analgesia, (ii) seizures and myoclonus, (iii) shivering, and (iv) early-onset pneumonia prevention. Writing groups conducted systematic literature searches of MEDLINE using PubMed focusing on contemporary publications in the past 30 years when temperature control was considered standard care. Each section reviews the scope and management of the controversy and provides a conclusion with suggested future research directions. The information in this review is intended to support providers with the implementation of recommendations made in clinical practice guidelines on post-resuscitation cardiac arrest care and should not necessarily supplant them.
Medication Dosing by Advanced Technologies: Promise on the Horizon but Not Without Risk.
Dager WE, Barletta JF, Erstad BL
Pharmacotherapy · 2026 Jan · PMID 41531316 · Publisher ↗
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Genotype Differences and Hydroxyurea Utilization Among Adults With Moderate to Severe Sickle Cell Disease.
Cheng SH, Novelli EM, Kang HA … +2 more , Newman TV, Suh K
Pharmacotherapy · 2026 Jan · PMID 41531305 · Full text
BACKGROUNDS: Hydroxyurea (HU) remains underutilized in adults with sickle cell disease (SCD) despite proven benefits. Current HU guidelines primarily target sickle cell anemia (SCA), overlooking other genotypes. OBJECTIV...
BACKGROUNDS: Hydroxyurea (HU) remains underutilized in adults with sickle cell disease (SCD) despite proven benefits. Current HU guidelines primarily target sickle cell anemia (SCA), overlooking other genotypes. OBJECTIVES: This study examined HU utilization patterns across genotypes among adults considered to have moderate to severe SCD manifestations by the 2014 National Heart, Lung, and Blood Institute (NHLBI) guideline criteria and identified factors associated with early HU use. METHODS: This retrospective cohort study analyzed electronic health records from the University of Pittsburgh Medical Center (2014-2024) of adults with SCD experiencing three or more vaso-occlusive crises (VOCs) within 12 months. HU utilization rates, stratified by genotype, were assessed at 30-, 90-, 180-, and 365-day intervals after the third VOC episode (index date). Multivariable logistic regression was used to identify factors associated with HU use within 90 days post-index. RESULTS: Among 411 adults with moderate to severe SCD (≥ 3 VOCs within a year), with a mean age of 42.4 ± 17.9 years and 61.3% female, only 19.5% received HU within 90 days post-index. Although 42.8% of SCA patients received HU within 1 year, only 8.0% of non-SCA patients received the treatment. The SCA genotype was the strongest predictor of HU use (odds ratio [OR] = 4.5, 95% confidence interval [CI]: 2.4-8.7), followed by pulmonary complications. Additional barriers included older age. CONCLUSION: Despite guideline recommendations since 2014, HU remains underutilized. Non-SCA patients meeting the severity threshold for HU use are consistently undertreated, highlighting an urgent need for studies establishing HU safety and efficacy in non-SCA genotypes. Future studies should also address age barriers to optimize HU use.
Harnessing the Power of Artificial Intelligence to Enhance Drug Therapy Research.
Baker WL, Chan A
Pharmacotherapy · 2026 Mar · PMID 41531203 · Publisher ↗
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