Pharmacotherapy [JOURNAL]
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200 papers
Challenges in renally eliminated medication use: Evaluating cystatin C and serum creatinine eGFR discordance.
Hernandez BN, Wieruszewski PM, Barreto JN … +9 more , Cole KC, Damani S, Kane-Gill SL, Kashani KB, Kelly E, Rule AD, Teaford HR, Zand J, Barreto EF
Pharmacotherapy · 2024 Dec · PMID 39601345 · Full text
BACKGROUND: Accurately estimating glomerular filtration rate (GFR) is crucial for dosing medications in hospitalized patients. Due to limitations of serum creatinine for GFR estimation, serum cystatin C (CysC) has been e...
BACKGROUND: Accurately estimating glomerular filtration rate (GFR) is crucial for dosing medications in hospitalized patients. Due to limitations of serum creatinine for GFR estimation, serum cystatin C (CysC) has been explored as an alternative functional kidney biomarker. This study assessed discordance between eGFR and eGFR in a large sample of hospitalized patients and examined the frequency of renally eliminated medications affected by eGFR discordance. METHODS: This multisite historical study included adults hospitalized between 2011 and 2023 with CysC and serum creatinine reported within 24 h of each other. The first concurrent biomarker pair for each patient was analyzed. eGFR discordance and use of renally eliminated medications were described. RESULTS: 17,718 hospitalized patients with concurrent creatinine and CysC assessments were included. The median eGFR was 65 mL/min, and the eGFR was 46 mL/min. The median absolute difference of eGFR-eGFR was 15 mL/min, and 7972 patients (45%) had a > 30% absolute difference. There was a significantly greater percentage of patients with an eGFR <30 mL/min based on eGFR (26%) compared to eGFR (15%) (p < 0.001). Patients were prescribed an average of 20 medications in the 24 h surrounding the concurrent biomarker assessment. Renally eliminated medications accounted for 39% ± 13% of medication orders, and 80% of patients with eGFR discordance were prescribed five or more renally eliminated medications. CONCLUSION: Substantial eGFR discordance between eGFR and eGFR was observed in hospitalized patients, which directly affects the dosing of renally eliminated medications. Further research is needed to optimize the pharmacotherapy of renally eliminated medications with discordant GFR assessments to improve medication safety and effectiveness.
Aztreonam-avibactam: The dynamic duo against multidrug-resistant gram-negative pathogens.
Al Musawa M, Bleick CR, Herbin SR … +3 more , Caniff KE, Van Helden SR, Rybak MJ
Pharmacotherapy · 2024 Dec · PMID 39601336 · Full text
Antimicrobial resistance poses a significant public health challenge, particularly with the rise of gram-negative hospital-acquired infections resistant to carbapenems. Aztreonam-avibactam (ATM-AVI) is a promising new co...
Antimicrobial resistance poses a significant public health challenge, particularly with the rise of gram-negative hospital-acquired infections resistant to carbapenems. Aztreonam-avibactam (ATM-AVI) is a promising new combination therapy designed to combat multidrug-resistant (MDR) gram-negative bacteria, including those producing metallo-β-lactamases (MBLs). Aztreonam, a monobactam antibiotic, is resistant to hydrolysis by MBLs but can be degraded by other β-lactamases. Avibactam, a novel non-β-lactam β-lactamase inhibitor, effectively neutralizes extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases, restoring aztreonam's efficacy against resistant pathogens. This review covers the chemistry, mechanisms of action, spectrum of activity, pharmacokinetics, pharmacodynamics, and clinical efficacy of ATM-AVI. ATM-AVI combination has shown efficacy against a wide range of resistant Enterobacterales and other gram-negative bacteria in both in vitro and clinical studies. Pharmacokinetic and pharmacodynamic analyses demonstrate that ATM-AVI maintains effective drug concentrations in the body, with dose adjustments recommended for patients with renal impairment. Clinical trials, including the REVISIT and ASSEMBLE studies, have demonstrated the safety and efficacy of ATM-AVI in treating complicated intra-abdominal infections (cIAI), urinary tract infections (UTIs), and hospital-acquired pneumonia (HAP) caused by MDR gram-negative pathogens. The European Medicines Agency (EMA) has approved ATM-AVI for these indications, and further research is ongoing to optimize dosing regimens and expand its clinical use. This combination represents a critical advancement in the fight against antimicrobial resistance, offering a new therapeutic option for treating severe infections caused by MDR gram-negative, including MBL-producing, bacteria.
Utilization and associated factors of TPMT testing among Australian adults receiving thiopurines: A national retrospective data-linkage study.
Yiu CH, Ianni BD, Fujita K … +3 more , Tan ECK, Hilmer SN, Lu CY
Pharmacotherapy · 2025 Jan · PMID 39587965 · Publisher ↗
INTRODUCTION: Thiopurine drugs are metabolized by thiopurine methyltransferase (TPMT) and low TPMT activity can result in severe adverse drug reactions. Therefore, TPMT testing is recommended for individuals receiving th...
INTRODUCTION: Thiopurine drugs are metabolized by thiopurine methyltransferase (TPMT) and low TPMT activity can result in severe adverse drug reactions. Therefore, TPMT testing is recommended for individuals receiving thiopurines to reduce the risk of toxicity. OBJECTIVES: The objectives of this study were to assess the rate of TPMT testing among individuals receiving thiopurines and explore factors associated with undergoing TPMT testing in Australia. METHODS: This retrospective cohort study utilized administrative data from the Pharmaceutical Benefits Scheme (PBS), Medicare Benefits Schedule (MBS), and the 2021 Census, accessed via the Person Level Integrated Data Asset (PLIDA) at the Australian Bureau of Statistics (ABS) DataLab. Individuals receiving thiopurines aged 18 years or above were identified using PBS data and exposure to TPMT testing was determined using MBS data. Multivariate logistic regression was performed to identify factors associated with TPMT testing. RESULTS: A total of 62,574 prevalent thiopurine users were identified between 2020 and 2022. Of these, 20,327 (32.5%) underwent TPMT testing (2011-2022). The most significant factor associated with TPMT testing was having at least one thiopurine medication prescribed by a medical specialist (adjusted odds ratio [aOR] 2.12, 95% confidence interval [CI] 2.02-2.22), compared to having medication solely prescribed by primary care physicians (PCPs). Other significant factors associated with TPMT testing included speaking a non-English language at home (aOR 1.29, 95% CI 1.22-1.36), having no chronic health conditions (aOR 1.18, 95% CI 1.13-1.24), not requiring assistance with core activities (aOR 1.16, 95% CI 1.08-1.23), and having a higher educational attainment (aOR 1.11, 95% CI 1.06-1.11). Compared to living in major cities, individuals living in remote areas were significantly less likely to undergo testing (aOR 0.49, 95% CI 0.39-0.60). CONCLUSION: Our study highlights the low utilization of TPMT testing in Australia and suggests the need for targeted interventions to address disparities and improve TPMT testing.
Association between mineralocorticoid receptor antagonists and kidney harm: A systematic review and meta-analysis of randomized controlled trials.
Mitsuboshi S, Morizumi M, Imai S … +2 more , Hori S, Kotake K
Pharmacotherapy · 2025 Jan · PMID 39578707 · Publisher ↗
Conflicting data have been reported on the association between mineralocorticoid receptor antagonists (MRAs) and acute kidney injury (AKI). This systematic review and meta-analysis aimed to evaluate whether MRAs affect t...
Conflicting data have been reported on the association between mineralocorticoid receptor antagonists (MRAs) and acute kidney injury (AKI). This systematic review and meta-analysis aimed to evaluate whether MRAs affect the risk of AKI. MEDLINE via PubMed, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov website were comprehensively searched to extract all relevant studies. Randomized controlled trials (RCTs) were selected that compared MRA versus placebo or no treatment and had study populations consisting of patients with heart or kidney disease. The primary outcome was AKI. The secondary outcome was kidney injury, including AKI and non-AKI. Thirty-three studies were included in the meta-analysis. MRAs were not associated with an increased risk of AKI (risk ratio [RR] 1.13, 95% confidence interval [CI] 0.88-1.46, p = 0.29, I = 15%, 18,065 patients, 13 RCTs, moderate certainty). For the secondary outcome, MRAs were associated with an increased risk of kidney injury (RR 1.52, 95% CI 1.24-1.87, p < 0.01, I = 48%, 27,492 patients, 33 RCTs, low certainty). In particular, only canrenone (RR 5.39, 95% CI 2.17-13.37, p < 0.01) and spironolactone (RR 1.78, 95% CI 1.48-2.14, p < 0.01) were associated with an increased risk of kidney injury. However, eplerenone and finerenone seem not to increase the risk of kidney injury in patients with heart or kidney disease. The selection of MRAs might influence the risk of kidney-associated events. Further studies focusing on individual MRAs may be needed to clarify these differences.
Update and narrative review of avian influenza (H5N1) infection in adult patients.
Aldhaeefi M, Rungkitwattanakul D, Saltani I … +4 more , Muirhead A, Ruehman AJ, Hawkins WA, Daftary MN
Pharmacotherapy · 2024 Nov · PMID 39548738 · Publisher ↗
The avian influenza is a serious infection caused by influenza virus that is native to birds. Avian influenza remains a global challenge due to high transmission and mortality rates. The highly pathogenic strain of H5N1...
The avian influenza is a serious infection caused by influenza virus that is native to birds. Avian influenza remains a global challenge due to high transmission and mortality rates. The highly pathogenic strain of H5N1 resulted in significant outbreaks and deaths globally since the late 1800s. The most recent outbreaks in wild birds, domestic birds, and cows with some genetic variations and mutations among H5N1 strains has raised major concerns about potential transmission and public health risks. Symptoms range from asymptomatic to mild flu-like illness to severe illness that requires hospitalization. There are multiple vaccines in development for humans to protect against avian influenza, specifically the H5N1 virus. This includes a cell-based vaccine approved by the FDA for people aged 6 months and older who are at higher risk of exposure to the H5N1 virus called Audenz. Chemoprophylaxis against avian influenza following a suspected exposure should be started as soon as possible or no later than 48 h, and it is recommended to be continued for 7 days. The majority of avian influenza viruses are susceptible to neuraminidase inhibitors and cap-dependent endonuclease inhibitor. Neuraminidase inhibitors are the mainstay of the avian influenza treatment and includes oseltamivir, peramivir, and zanamivir. Baloxavir marboxil is a cap-dependent endonuclease inhibitor. This clinical review aims to highlight the background, epidemiology, clinical presentation, complications and current treatment and prevention strategies for avian influenza H5N1.
Precision medicine to identify, prevent, and treat pediatric obesity.
Tillman EM, Mertami S
Pharmacotherapy · 2024 Dec · PMID 39548737 · Full text
Pediatric obesity is a growing health concern that has many secondary adverse health implications. Personalized medicine is a tool that can be used to optimize diagnosis and treatments of many diseases. In this review, w...
Pediatric obesity is a growing health concern that has many secondary adverse health implications. Personalized medicine is a tool that can be used to optimize diagnosis and treatments of many diseases. In this review, we will focus on three areas related to the genetics of pediatric obesity: (i) genetic causes predisposing to pediatric obesity, (ii) pharmacogenomics that may predict weight gain associated with pharmacotherapy, and (iii) pharmacogenomics of anti-obesity pharmacotherapy. This narrative review evaluates genetic cause of pediatric obesity and how genetic findings can be used to optimize pharmacotherapy to minimize weight gain and optimize obesity treatment in pediatric patients. Pediatric obesity has many genetic causes including genomic obesity syndromes and monogenic obesity disorders. Several genetic etiologies of obesity have current or emerging targeted genetic therapies. Pharmacogenomic (PGx) targets associated with pharmacotherapy-induced weight gain have been identified for antipsychotic, antiepileptic, antidepressant therapies, and steroids, yet to date no clinical guidelines exist for application use of PGx to tailor pharmacotherapy to avoid weight gain. As legislation evolves for genetic testing coverage and technology advances, this will decrease cost and expand access to genetic testing. This will result in identification of potential genetic causes of obesity and genes that predispose to pharmacotherapy-induced weight gain. Advances in precision medicine can ultimately lead to development of clinical practice guidelines on how to apply genetic findings to optimize pharmacotherapy to treat genetic targets of obesity and avoid weight gain as an adverse event associated with pharmacotherapy.
External evaluation of neonatal vancomycin population pharmacokinetic models: Moving from first-order equations to Bayesian-guided therapeutic monitoring.
Blouin M, Métras MÉ, Gaudreault C … +7 more , Dubé MH, Boulanger MC, Cloutier K, El Hassani M, Yaliniz A, Viel-Thériault I, Marsot A
Pharmacotherapy · 2024 Dec · PMID 39544156 · Full text
INTRODUCTION: Guidelines for vancomycin therapeutic monitoring recommend using a Bayesian approach with a population pharmacokinetic model to estimate the 24 h area under the concentration-time curve over first-order equ...
INTRODUCTION: Guidelines for vancomycin therapeutic monitoring recommend using a Bayesian approach with a population pharmacokinetic model to estimate the 24 h area under the concentration-time curve over first-order equations. Thus, we performed an external evaluation of population pharmacokinetic models of vancomycin in neonates and compared Bayesian results with those observed in clinical practice via pharmacokinetic equations to improve therapeutic monitoring by proposing optimized initial dosing nomograms and assessing the feasibility of reduced blood sampling strategies using the most predictive models. METHODS: Models were identified from the literature and evaluated via an external neonatal population. A priori predictive performance was first assessed by prediction-based diagnostics, then by simulation-based diagnostics and a posteriori analyses only if deemed satisfactory; model-informed vancomycin exposure was also compared with reference first-order pharmacokinetic equations. The best-performing models were ultimately subjected to Monte Carlo simulations to develop new initial dosing nomograms offering the highest probability of achieving therapeutic target. RESULTS: A total of 28 population pharmacokinetic models were evaluated in the external dataset, which includes 72 neonates and 380 vancomycin concentrations. Eleven models had an adequate predictive performance with bias ≤ ± 15% and imprecision 30%, while the Bayesian approach yielded over 75% agreement with reference exposure values in most cases. Nonetheless, Capparelli et al. and Mehrotra et al. models performed the best overall, showing the lowest imprecisions of 16.8% and 16.9%, respectively; both models recommended higher dosage regimens than the theoretical nomogram currently applied to favor therapeutic target attainment. DISCUSSION: We externally evaluated numerous neonatal population pharmacokinetic models of vancomycin and used the most predictive ones to advocate new initial dosing nomograms. Clinical implementation of the Bayesian approach could reduce the time needed to reach therapeutic target and limit the number of blood samples in newborns compared with traditional pharmacokinetic equations.
The gray area of scientific adequacy.
DeVane CL
Pharmacotherapy · 2024 Sep · PMID 39499255 · Publisher ↗
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Cannabinoids for obstructive sleep apnea: A systematic review.
Boylan PM, Santibañez M, Thomas J … +3 more , Weeda E, Noel ZR, Caballero J
Pharmacotherapy · 2024 Nov · PMID 39498540 · Publisher ↗
Cannabinoids have emerged as a potential treatment for obstructive sleep apnea (OSA). This systematic review aimed to summarize the efficacy and safety of cannabinoids to treat OSA. Databases including Ovid MEDLINE, EMBA...
Cannabinoids have emerged as a potential treatment for obstructive sleep apnea (OSA). This systematic review aimed to summarize the efficacy and safety of cannabinoids to treat OSA. Databases including Ovid MEDLINE, EMBASE, Scopus, PsycINFO, and International Pharmaceutical Abstracts were searched; experimental and observational studies were eligible for inclusion. One-hundred seventy unique records were screened, and nine studies included: five full-text studies and four published abstracts. The five full-text studies were judged for quality appraisal: two studies deemed at low risk for bias, one study deemed to have some concerns for bias, and two studies deemed to have high risk for bias. Seven of nine total studies were experimental designs and evaluated dronabinol, and the other two studies were observational designs evaluating cannabis. The range of cannabinoid therapy duration spanned from 1 to 6 weeks, and the median duration was 3 weeks. Eight of nine total studies reported statistically significant, positive OSA outcomes due to cannabinoid therapy including reductions in the apnea hypopnea index and improvements in patient-reported daytime sleepiness scales. Between 70% and 80% of study participants reported neuropsychiatric and gastrointestinal adverse events attributable to cannabinoids. The American Academy of Sleep Medicine does not recommend using cannabinoids to treat OSA due to a lack of long-term safety and efficacy data. This systematic review found similar limitations, with the median cannabinoid treatment duration being only 3 weeks. Adequately powered experimental trials over longer time frames are necessary to more completely assess the long-term efficacy and safety of cannabinoids in the treatment of OSA and its effects on common comorbid conditions, such as obesity and cardiovascular disease.
ECLIPSES: Early initiation of sodium glucose cotransporter-2 inhibitors for cardiovascular protection in patients with type 2 diabetes following acute coronary syndrome and subsequent coronary artery bypass graft surgery.
Makortoff L, Then KL, Dutchak M … +3 more , Lin M, Youngson E, Harten C
Pharmacotherapy · 2024 Nov · PMID 39460440 · Publisher ↗
INTRODUCTION: There is a paucity of data evaluating early initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with diabetes following acute coronary syndrome (ACS) and coronary artery bypass graf...
INTRODUCTION: There is a paucity of data evaluating early initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with diabetes following acute coronary syndrome (ACS) and coronary artery bypass graft surgery (CABG). OBJECTIVES: To describe the efficacy and safety of SGLT2i initiated early after CABG in patients with type 2 diabetes who experienced ACS. METHODS: This is a retrospective cohort study of patients with type 2 diabetes (T2DM) who experienced ACS and subsequent CABG with follow up at 3 and 12 months. Patients who filled a SGLT2i prescription within 14 days of discharge were allocated to the SGLT2i group and those who did not were included in the no SGLT2i group. The primary efficacy end point was first occurrence of a 4-point Major Adverse Cardiovascular Event (MACE), and the primary safety end point was a composite of hypoglycemia, hypotension, diabetic ketoacidosis, acute kidney injury, and urinary tract infection. Secondary end points included a comparative analysis of the primary outcome, 30-day readmission rates, and subgroup analyses of key populations. RESULTS: A total of 1629 patients were included: 226 received a SGLT2i within 14 days of discharge and 1403 did not. At 12 months, 8.9% and 15.3% of patients experienced MACE in the SGLT2i and no SGLT2i groups, respectively (adjusted Hazard Ratio [aHR] 0.65, 95% confidence interval [CI] 0.41-1.04). The primary safety outcome occurred in 12.0% of the SGLT2i group and 19.1% of the no SGLT2i group at 12 months (aHR 0.68, 95% CI 0.45-1.01). CONCLUSION: Early initiation of SGLT2i use was not associated with a reduction in MACE in patients with T2DM who experienced ACS and underwent subsequent CABG surgery. However, no apparent safety concerns were identified. Adequately powered trials are required to confirm this finding.
Sex differences in LDL-C reduction response to evolocumab: A propensity score matching analysis.
He YQ, Wei YQ, Huang GM … +5 more , Liu GP, Lin ZQ, Liu TT, Jiang X, Lu JJ
Pharmacotherapy · 2024 Nov · PMID 39441027 · Publisher ↗
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have been shown to improve cardiovascular outcomes by reducing low-density lipoprotein cholesterol (LDL-C). However, sex differences in the ef...
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have been shown to improve cardiovascular outcomes by reducing low-density lipoprotein cholesterol (LDL-C). However, sex differences in the efficacy of evolocumab remain unclear. This study aimed to investigate sex differences in the efficacy of evolocumab using real-world data. METHOD: Data were collected from the First Affiliated Hospital of Guangxi Medical University. A total of 416 eligible patients were selected from 1463 patients treated with evolocumab for secondary prevention. Clinical data, including individual characteristics and lipids profiles, were recorded. Propensity score matching (PSM) was used to control for potential confounders, with covariates including age, body mass index, smoking status, and diabetes. All eligible participants were propensity-matched 1:1 for female versus male with a match tolerance of 0.02. The efficacy of evolocumab in females and males was compared by PSM-adjusted analysis. RESULTS: In the PSM analysis, a significant difference was found in the relative percentage reduction of LDL-C between females and males (-42.7% vs. -54.4%, p < 0.001). In addition, the absolute LDL-C reduction was lower in females compared to males (interquartile range: -1.5 [-2.2, -0.8] mmol/L vs. -1.9 [-2.5, -1.0] mmol/L, p = 0.018). The rate of target LDL-C attainment was lower in females than in males after treatment with evolocumab (21.6% vs. 39.8%, p = 0.009). CONCLUSION: These results suggest that males have a better response to evolocumab in term of LDL-C reduction compared to females.
Use of proton pump inhibitors and risk of severe COVID-19: A case-control study in United States Medicare beneficiaries.
Mosholder AD, Izurieta HS, Zhang R … +13 more , Shangguan S, Lu Y, Akhtar S, Wernecke M, He J, Chillarige Y, Feng Y, Avagyan A, Leishear K, Forshee RA, MaCurdy TE, Kelman JA, Graham DJ
Pharmacotherapy · 2024 Oct · PMID 39425479 · Publisher ↗
BACKGROUND: Concerns have been raised regarding proton pump inhibitor (PPI) use and risk of severe coronavirus disease 2019 (COVID-19). Observational studies have yielded heterogeneous results and were subject to importa...
BACKGROUND: Concerns have been raised regarding proton pump inhibitor (PPI) use and risk of severe coronavirus disease 2019 (COVID-19). Observational studies have yielded heterogeneous results and were subject to important methodological limitations. AIMS: To examine the association between the receipt of PPIs and risk of COVID-19 hospitalizations and severe in-hospital outcomes or death. METHODS: Case-control study among Medicare fee-for-service beneficiaries 66+ years old with gastroesophageal reflux disorder (GERD). Within this population, we identified cases by an incident hospital discharge diagnosis of COVID-19 from April 1 to December 11, 2020, using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) U07.1, and randomly selected up to 10 controls per case, matched on date and neighborhood. We defined PPI use as a prescription providing ≥15 days of supply in the 30 days before admission, with H2-receptor antagonist (H2RA) use as the reference to account for indication. We analyzed uncomplicated hospitalizations and hospitalizations with severe outcomes (intensive/coronary care unit admission, invasive mechanical ventilation, or death), estimating odds ratios (ORs), and 95% confidence intervals (CIs) with multinomial conditional logistic regression adjusted for demographics, comorbidities, chronic medications, and health care utilization. RESULTS: We matched 25,867 uncomplicated and 12,954 severe hospitalized COVID-19 cases to 146,972 and 73,104 controls, respectively. Cases tended to be older and have more comorbidities. Relative to H2RA use, we found no association of PPI use with uncomplicated COVID-19 hospitalization (OR 0.99, 95% CI 0.93-1.06) or severe COVID-19 hospitalization (OR 1.00, 95% CI 0.91-1.10). CONCLUSIONS: Relative to H2RA use, PPI use was not associated with uncomplicated or severe COVID-19 hospitalizations among Medicare beneficiaries with GERD.
Neurodevelopmental outcomes in children prenatally exposed to opioid maintenance treatment: A population-based study.
Hasan M, Meador KJ, Brothers TN … +6 more , Wang S, Lewkowitz AK, Ward KE, Slaughter JL, Zhang Y, Wen X
Pharmacotherapy · 2024 Oct · PMID 39415648 · Full text
BACKGROUND AND OBJECTIVES: Opioid maintenance treatment (OMT), with methadone or buprenorphine, is a key approach for managing opioid use disorder (OUD) during pregnancy. Despite buprenorphine's superior short-term outco...
BACKGROUND AND OBJECTIVES: Opioid maintenance treatment (OMT), with methadone or buprenorphine, is a key approach for managing opioid use disorder (OUD) during pregnancy. Despite buprenorphine's superior short-term outcomes, its long-term effects remain understudied. This study aims to evaluate the effects of prenatal OMT exposure on the incidence of childhood neurodevelopmental disorders (NDDs) considering timing effect. METHODS: A retrospective cohort study using Rhode Island Medicaid data linked to vital statistics from 2008 to 2018 was conducted. The study included pregnancies having live birth from 2008 to 2016 with continuous Medicaid insurance and OUD diagnosis within 3 months preceding conception until delivery. At least one buprenorphine dispensing or a claim of methadone was required for exposure definition. Exposure was evaluated during early (0-90 days) or late (>90 days) gestation, or at any pregnancy phase. NDDs, including autism, attention-deficit/hyperactivity disorder (ADHD), learning disabilities, speech/language disorders, developmental coordination disorder, intellectual disability, and behavioral disorders, were identified using validated algorithms. Applying Cox proportional-hazard models with propensity score overlap weighting, adjusted hazard ratios (aHR) were calculated, mitigating potential confounders. Children were followed up from birth until NDD diagnosis, disenrollment, or study end. RESULTS: Of 416 mother-child dyads with OUD, 40% used methadone and 20% had buprenorphine exposure during pregnancy. NDDs were observed in 36% of children with early methadone exposure compared to 17% in the early buprenorphine exposed group (aHR: 2.75; 95% confidence interval [CI]: 1.42-5.35). Further comparison to late buprenorphine exposure, late methadone exposure was associated with higher NDD risk (aHR: 2.05; 95% CI: 1.09-3.86). Compared to unexposed group, children exposed to methadone during early and late periods showed higher NDD incidences (aHR: 2.33; 95% CI: 1.51-3.60 and aHR: 2.42; 95% CI: 1.54-3.80, respectively). DISCUSSION: The study suggests that buprenorphine is a good treatment option for OUD during pregnancy due to minimal long-term neurodevelopmental impacts on children. However, further extensive research is necessary to rule-out potential confounding.
Association between gastroprotective agents and acute kidney injury in patients receiving non-steroidal anti-inflammatory drugs: Analysis of a Japanese hospital-based database.
Mitsuboshi S, Imai S, Kizaki H … +1 more , Hori S
Pharmacotherapy · 2024 Nov · PMID 39400376 · Full text
INTRODUCTION: The concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) potentially increases the risk of acute kidney injury (AKI). However, the risk of AKI has not been com...
INTRODUCTION: The concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) potentially increases the risk of acute kidney injury (AKI). However, the risk of AKI has not been comprehensively assessed for the concomitant use of NSAIDs with gastroprotective agents such as misoprostol and PPIs. The objective of this study was to evaluate whether the use of various gastroprotective agents affects the risk of AKI in patients receiving NSAIDs. METHODS: The data analyzed were obtained from the JMDC hospital-based administrative claims database between April 2014 and August 2022. Histamine-2 receptor antagonists (H2RAs) were compared with PPIs or misoprostol in patients receiving NSAIDs. The primary outcome was the incidence of AKI. The covariates considered were age and sex, admission to intensive care unit, presence of comorbidities based on the modified Charlson Comorbidity Index, and use of renin-angiotensin system inhibitors, loop diuretics, other diuretics, and lithium. AKI was identified by changes in serum creatinine. The distribution of AKI was analyzed using the log-rank test, and estimates of the incidence of AKI were compared among the groups using a Cox proportional hazards model with time-varying variables. Models were adjusted using a doubly robust method that accounts for the inverse probability of treatment weighting at baseline while adjusting for covariates. RESULTS: After screening, 11,688 patients were eligible for inclusion (1729 for H2RAs, 368 for misoprostol, and 9591 for PPIs). AKI occurred in 0.5% of H2RA recipients and 1.1% of PPI recipients; no AKI was observed in the misoprostol group. Compared with H2RAs, the risk of AKI tended to be higher with PPIs (adjusted hazard ratio 1.83, 95% confidence interval 0.92-3.63, p = 0.08). CONCLUSION: Compared with H2RAs, PPIs may increase the risk of AKI in patients receiving NSAIDs, although no statistically significant difference was observed. Further research is required to assess the risk trade-off with consideration of both peptic ulcer prevention and the increased risk of AKI in patients concurrently treated with NSAIDs and H2RAs, misoprostol, or PPIs.
Albuminuria-based stratification of end-stage kidney disease progression and mortality with sodium-glucose cotransporter 2 inhibitors (SGLT2i): A retrospective cohort study in type 2 diabetes and chronic kidney disease.
Chang TJ, Lee YC, Wu LC … +1 more , Chang CH
Pharmacotherapy · 2024 Nov · PMID 39382257 · Publisher ↗
BACKGROUND: Clinical trials have shown the kidney-protective benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, their real-world impact, particularly across varying levels of albuminuria, remains le...
BACKGROUND: Clinical trials have shown the kidney-protective benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, their real-world impact, particularly across varying levels of albuminuria, remains less well understood. This study aimed to evaluate the association of SGLT2i, compared with other oral glucose-lowering drugs, with end-stage kidney disease (ESKD) progression in patients with type 2 diabetes and chronic kidney disease (CKD) stratified by urine albumin-to-creatinine ratio (UACR) levels. METHODS: Using data from a national database spanning from 2016 to 2021, the study included patients with type 2 diabetes and CKD with estimated glomerular filtration rates (eGFRs) below 60 mL/min/1.73 m and who started on SGLT2i or other oral glucose-lowering drugs. Patients were stratified into groups by UACR ≥300 mg/g and <300 mg/g. Propensity score matching was used to minimize confounding, and progression to ESKD was evaluated using competing risks and Cox proportional-hazards models. All-cause mortality was also analyzed. RESULTS: Following propensity score matching, 18,514 patients in the severely increased albuminuria group (UACR ≥300 mg/g) were tracked, with 2.6% progressing to ESKD over 3 years. In contrast, only 0.3% of the 26,946 patients with UACR <300 mg/g progressed to ESKD. SGLT2i use was associated with a 30% reduction in risk of ESKD progression, compared with the use of other oral glucose-lowering drugs, in the severely increased albuminuria group (hazard ratio[HR]: 0.70, 95% confidence interval [CI]: 0.61-0.80). In the lower albuminuria group, no significant association was evident, though there was a nonsignificant trend toward protection over time. A consistent reduction in mortality risk was observed across all albuminuria levels. CONCLUSIONS: SGLT2i are associated with a reduction in the progression to ESKD among patients with severely increased albuminuria, with less pronounced effects observed in those with lower albuminuria levels, suggesting variability in renal outcomes based on albuminuria severity. The consistent survival benefit across all albuminuria levels supports the potential utility of SGLT2i in diabetes and CKD treatment strategies, emphasizing the need for more targeted research.
Impacts of age and BMI on vancomycin model choice in a Bayesian software: Lessons from a very large multi-site retrospective study.
Hughes MA, Lee T, Faldasz JD … +1 more , Hughes JH
Pharmacotherapy · 2024 Oct · PMID 39382218 · Publisher ↗
BACKGROUND: Model-informed precision dosing (MIPD) optimizes drug doses based on pharmacokinetic (PK) model predictions, necessitating careful selection of models tailored to patient characteristics. This study evaluates...
BACKGROUND: Model-informed precision dosing (MIPD) optimizes drug doses based on pharmacokinetic (PK) model predictions, necessitating careful selection of models tailored to patient characteristics. This study evaluates the predictive performance of various vancomycin PK models across diverse age and BMI categories, drawing insights from a large multi-site database. METHODS: Adults receiving vancomycin intravenous therapy at United States health systems between January 1, 2022, and December 31, 2023, were included. Patient demographics, vancomycin administration records, and therapeutic drug monitoring levels (TDMs) were collected from the InsightRX database. Age and body mass index (BMI)-based subgroups were formed to assess model performance, with predictions made iteratively. The optimal model for each age-BMI subgroup was chosen based on predefined criteria: models were filtered for mean percentage error (MPE) ≤ 20% and normalized root mean squared error (RMSE) < 8 mg/L, and then the most accurate among them was selected. RESULTS: A total of 384,876 treatment courses across 155 US health systems were analyzed, contributing 841,604 TDMs. Eleven models were compared, showing varying accuracy across age-BMI categories (41%-73%), with higher accuracy observed once TDMs were available for Bayesian estimates of individual PK parameters. Models performed more poorly in younger adults compared to older adults, and the optimal model differed depending on age-BMI categories and prediction methods. Notably, in the a priori period, the Colin model performed best in adults aged 18-64 years across most BMI categories; the Goti/Tong model performed best in the older, non-obese adults; and the Hughes model performed best in many of the obese categories. CONCLUSION: Our study identifies specific vancomycin PK models that demonstrate superior predictions across age-BMI categories in MIPD applications. Our findings underscore the importance of tailored model selection for vancomycin management, especially highlighting the need for improved models in younger adult patients. Further research into the clinical implications of model performance is warranted to enhance patient care outcomes.
Intravenous ketamine successfully treats treatment-resistant catatonia in schizophrenia: A case report.
Siddiqui A
Pharmacotherapy · 2024 Oct · PMID 39367688 · Publisher ↗
BACKGROUND: Benzodiazepines and electroconvulsive therapy (ECT) are mainstay treatments for catatonia, a potentially life-threatening psychomotor syndrome characterized by a range of symptoms, including immobility, mutis...
BACKGROUND: Benzodiazepines and electroconvulsive therapy (ECT) are mainstay treatments for catatonia, a potentially life-threatening psychomotor syndrome characterized by a range of symptoms, including immobility, mutism, stupor, posturing, and sometimes even agitation. It can be a manifestation of various underlying psychiatric or medical conditions, such as schizophrenia, mood disorders, or neurological disorders. When conventional treatments fail to alleviate symptoms, ketamine, a dissociative anesthetic, has emerged as a potential therapeutic option for catatonia. However, its precise mechanism of action in treating catatonia remains to be fully elucidated. The use of ketamine in treating treatment-resistant catatonia in patients with schizophrenia has not been described. METHODS: We describe a unique case of a 77-year-old female with schizophrenia for 15 years who presented with hallucinations, generalized weakness, immobility, stupor, and mutism consistent with severe catatonia. The electroencephalogram did not show seizures, and brain imaging was negative for stroke. Her catatonia was resistant to treatment with benzodiazepines and haloperidol. However, ECT was unavailable due to the COVID-19 pandemic. She was successfully treated with a single intravenous infusion of ketamine administered at a dose of 0.5 mg/kg over 40 min with complete rapid recovery and remained stable as an outpatient. RESULTS: Intravenous ketamine single infusion may be a safe and feasible option in schizophrenia patients with drug-resistant catatonia, particularly in patients for whom standard therapies are ineffective. However, its use should be approached cautiously due to the risk of exacerbation of psychosis in patients with schizophrenia. CONCLUSIONS: Further research is warranted to better understand the role of ketamine in the management of catatonia in this patient population.
Efficacy and safety of mirikizumab compared with currently approved biologic drugs for the treatment of ulcerative colitis: A systematic review and network meta-analysis.
Moćko P, Koperny M, Śladowska K … +3 more , Holko P, Kowalska-Bobko I, Kawalec P
Pharmacotherapy · 2024 Oct · PMID 39320112 · Publisher ↗
Ulcerative colitis (UC) is a serious health problem that requires a constant need to identify new effective drugs. The aim of this study was to assess the efficacy and safety of mirikizumab compared with other biologic d...
Ulcerative colitis (UC) is a serious health problem that requires a constant need to identify new effective drugs. The aim of this study was to assess the efficacy and safety of mirikizumab compared with other biologic drugs approved for the treatment of moderately to severely active UC. This systematic review with frequentist network meta-analysis (NMA) included randomized controlled trials (RCTs) that evaluated the use of adalimumab, golimumab, infliximab, mirikizumab, vedolizumab, and ustekinumab compared with placebo or with another approved biologic drug. The NMA was conducted using the netmeta R software package. The P score was used to determine the treatment ranking. A total of 14 RCTs were included in the analysis. No significant differences were observed in the incidence of clinical response and remission between mirikizumab and other drugs. Mirikizumab was superior to placebo for clinical response (induction: odds ratio [OR] = 2.38; 95% confidence interval [CI]: 1.63-3.48; maintenance: OR = 3.31, 95% CI: 1.59-6.89) and remission (induction: OR = 2.09, 95% CI: 1.20-3.63; maintenance: OR = 2.96; 95% CI: 1.62-5.40). The probability plot indicated that infliximab might be the most effective option in terms of both clinical response and remission (P score, 0.8971 and 0.8814, respectively) in induction phase. No significant differences were noted between the studied drugs in any adverse events (AEs), serious AEs (SAEs) and infections for the induction phase, and in any AEs, infections and serious infections for the maintenance phase. The drugs differed in terms of discontinuation due to AEs (induction and maintenance phases) as well as SAEs and serious infections (maintenance phase). Mirikizumab did not differ from other biologics in terms of clinical response and remission for both induction and maintenance phases in patients with UC. Mirikizumab during the induction phases achieved rank 3 for clinical response and rank 5 for clinical remission. Therefore, it represents a valuable treatment option. The lack of significant differences in the risk of AEs and SAEs suggests that mirikizumab has a similar safety profile to the other drugs.
Delirium event and associated treatment modifications among older adults with Alzheimer's disease: An interrupted time-series analysis of Medicare data.
Talwar A, Chatterjee S, Abughosh S … +3 more , Johnson M, Sherer J, Aparasu RR
Pharmacotherapy · 2024 Oct · PMID 39287108 · Publisher ↗
BACKGROUND: Both Alzheimer's disease (AD) and deliriogenic medications increase the risk of delirium in older adults. This study examined the association between delirium and the subsequent monthly use of anticholinergic...
BACKGROUND: Both Alzheimer's disease (AD) and deliriogenic medications increase the risk of delirium in older adults. This study examined the association between delirium and the subsequent monthly use of anticholinergic, sedative, and opioid medications in the 1 year after delirium in older adults with AD. METHODS: This comparative interrupted time series analysis involved adults (aged 65 years and older) with a diagnosis of AD initiating on cholinesterase inhibitors (ChEIs) based on 2013-2017 Medicare data. Separate patient-level segmented regression models were used for each outcome to evaluate changes in the cumulative anticholinergic burden (CAB), sedative load, and opioid load after the delirium/index event using a 12-month baseline and follow-up period among patients who had a delirium event and those without delirium (control group). Propensity score-based stabilized weights were utilized to balance baseline factors in the delirium and control groups. RESULTS: The study included 80,019 older adults with AD with incident ChEI use; 17.11% had delirium. There was an immediate decline in monthly CAB after the delirium event (mean estimate -0.86, p-value: 0.01) compared to the control group. A similar decline was observed when examining the sedative load (-0.06, p-value: 0.002) after the delirium event. However, there was no decline in opioid load (-0.50, p-value: 0.18). In the long term, CAB (0.13; p-value: <0.0001), sedative load (0.01; p-value: <0.001), and opioid load (0.07; p-value: 0.006) increased over the 1-year post-delirium period in the delirium group compared to those without delirium. CONCLUSION: This study found the burden of deliriogenic medications over the 1-year follow-up showed increasing trends in older adults with AD, even though there was some level shift in CAB and sedative load after the delirium event.
Influence of intravenous iron on bacterial infection risk immediately following kidney transplantation.
January SE, Dubrawka CA, Progar K … +2 more , Kurwicki K, Delos Santos R
Pharmacotherapy · 2024 Sep · PMID 39239762 · Publisher ↗
BACKGROUND: Kidney transplant recipients are at higher risk of infections due to immunosuppression, especially in the perioperative period after receiving induction therapy. Administration of iron has been linked to bact...
BACKGROUND: Kidney transplant recipients are at higher risk of infections due to immunosuppression, especially in the perioperative period after receiving induction therapy. Administration of iron has been linked to bacterial infections. This study investigated if receipt of intravenous iron at the time of kidney transplant increased bacterial infections post-transplant. METHODS: This single-center, retrospective study compared patients who received intravenous iron at the time of kidney transplant to those who did not. Patients were followed for 12 weeks after transplant. The primary outcome was incidence of bacterial infections following transplant; hemoglobin and transfusion needs were also examined. RESULTS: A total of 416 patients who received intravenous iron were compared to 416 patients who did not. Bacterial infections were similar between groups (14.4% iron group vs. 15.9% non-iron group). Intravenous iron did not influence bacterial infections on univariable or multivariable analyses when other infection confounders were accounted for. Patients who did not receive intravenous iron required more packed red blood cell transfusions in the 3 months following transplantation, but this was driven by factors other than intravenous iron as demonstrated by a post-hoc analysis. CONCLUSIONS: Intravenous iron did not increase the risk of bacterial infections in the immediate post-kidney transplant setting. Bacterial infections after transplant were associated with female sex, increasing age at transplant, receipt of transfusions, and increased duration of urinary catheters.
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