Dosing Regimens In Patients Research Articles

Evaluation of plasma levels of meropenem in septic patients during extracorporeal blood purification

The relevance. Meropenem is a broad-spectrum carbapenem antibiotic widely used to treat patients with sepsis / septic shock. Critically ill patients are usually supported with one of the forms extracorporeal blood purification. However, data on the effect of various extracorporeal support techniques on the pharmacokinetics and pharmacodynamics of meropenem are insufficient or contradictory.
 Aim: To evaluate the effectiveness of meropenem dosage regimens in the treatment of septic patients during extracorporeal blood purification.
 Materials and methods. Plasma concentrations of meropenem were monitored in three critically ill patients with sepsis or septic shock. Patients were treated using various extracorporeal support techniques. Meropenem was used as empirical antibacterial mono- or complex therapy (1 g every 8 or 12 hours). Meropenem concentrations in plasma were determined by validated assay methods on Acquity ultraefficient liquid chromatography (UPLC) H-Class system.
 Results. It is shown that the meropenem plasma concentration in critically ill patients changes significantly. It was found that the standard meropenem dosing regimens in patients with sepsis / septic shock during continuous hemodiafiltration do not ensure the achievement of the PK/PD target of 100% TMIC for sensitive strains (MIC2 mg/L) and for intermediate resistance pathogens (2MIC8 mg/L). Continuous hemofiltration and selective adsorption of lipopolysaccharide have a less pronounced effect on the clearance of meropenem.
 Conclusion. To increase the effectiveness of antibacterial therapy, it is necessary to conduct research aimed at developing protocols for dosing antibacterial drugs for the treatment of sepsis during extracorporeal blood purification.

Proposal of initial and maintenance dosing regimens with linezolid for renal impairment patients

BackgroundLinezolid is administered as a fixed dose to all patients despite evidence of overexposure and thrombocytopenia in renal impairment. The aims of this study were to evaluate the risk of thrombocytopenia and the utility of therapeutic drug monitoring (TDM), and to propose alternate dosing regimens in patients with renal impairment.MethodsWe retrospectively reviewed patients ≥13 years old for whom serum linezolid trough concentration (Cmin) was measured during linezolid treatment. Patients with episodes of infection were divided into groups by presence of renal impairment (RI group) or absence of renal impairment (non-RI group), and by use of Cmin-based TDM (TDM group) or not (non-TDM group) during linezolid treatment.ResultsIn the 108 patients examined by multivariable analyses, renal impairment was independently associated with increased risk of thrombocytopenia (OR 3.17, 95%CI 1.10–9.12) and higher Cmin. Analysis of the utility of TDM in the RI group showed that clinical failure rate was significantly lower in the TDM subgroup than in the non-TDM subgroup. Furthermore, in the RI group, dosage adjustments were needed in 90.5% of the TDM subgroup. All episodes administered a reduced dose of 300 mg every 12 h in the RI group showed Cmin ≥ 2.0 mg/L. Additional analysis of 53 episodes in which Cmin was measured within 48 h after starting administration showed that the initial standard dose for 2 days was sufficient to rapidly reach an effective therapeutic concentration in the RI group.ConclusionsEmpirical dose reduction to 300 mg every 12 h after administration of the initial fixed dose for 2 days and Cmin-based TDM may improve safety outcomes while maintaining appropriate efficacy among patients with renal impairment.

Evaluating Safety, Tolerability, and Efficacy of Subcutaneous Human Immunoglobulin 16.5% Administered at Modified Dosing Regimens in Patients with Primary Immunodeficiency Diseases – Study Design

Immunoglobulin (Ig) concentrates have been successfully used to treat patients with primary immunodeficiency disorders (PID). Many patients opt to use subcutaneous route of administration (SCIg) for the convenience, flexibility and minimal systemic side effects. This study plans to evaluate safety, tolerability, and efficacy of a SCIg 16.5% at modified infusion regimens in adult and pediatric PID patients.

Real-world experience of adalimumab in the treatment of hidradenitis suppurativa

Real-world experience of adalimumab in the treatment of hidradenitis suppurativa

Comparison of shock reversal with high or low dose hydrocortisone in intensive care unit patients with septic shock: A retrospective cohort study.

This study aims to describe differences in shock reversal between hydrocortisone 200mg and 300mg per day dosing regimens in patients with septic shock. This is a multi-center retrospective study including patients admitted to intensive care units with septic shock receiving vasopressors and hydrocortisone between 2013 and 2018. We compared patients who received low dose hydrocortisone (50mg every 6h) versus high dose hydrocortisone (100mg every 8h) on the primary outcome of shock reversal. 319 patients (low dose group, n=134 and high dose group, n=185) were included. In the multivariate regression model, high-dose steroids were associated with shock reversal [OR (95% CI)=2.278 (1.063-4.880), p=0.034]. This was not confirmed in the propensity score matched analysis [OR (95% CI) =2.202 (0.892-5.437), p=0.087]. High dose steroids were associated with a lower need for additional vasopressor therapy (22% vs. 34%, p=0.012) and lower shock recurrence (6.7% vs. 16%, p=0.013), which was confirmed with propensity score matching. Low and high dose hydrocortisone have similar rates of shock reversal in septic shock patients. Hydrocortisone 100mg every 8h may reduce rates of recurrence of shock and reduce the need for additional vasopressors.

Differential Effects of 1α,25-Dihydroxyvitamin D3 on the Expressions and Functions of Hepatic CYP and UGT Enzymes and Its Pharmacokinetic Consequences In Vivo.

The compound 1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is the active form of vitamin D3 and a representative ligand of the vitamin D receptor (VDR). Previous studies have described the impacts of 1,25(OH)2D3 on a small number of cytochrome P450 (CYP) and uridine diphosphate-glucuronyltransferase (UGT) enzymes, but comparatively little is known about interactions between several important CYP and UGT isoforms and 1,25(OH)2D3 in vitro and/or in vivo. Thus, we investigated the effects of 1,25(OH)2D3 on the gene and protein expressions and functional activities of selected CYPs and UGTs and their impacts on drug pharmacokinetics in rats. The mRNA/protein expressions of Cyp2b1 and Cyp2c11 were downregulated in rat liver by 1,25(OH)2D3. Consistently, the in vitro metabolic kinetics (Vmax and CLint) of BUP (bupropion; a Cyp2b1 substrate) and TOL (tolbutamide; a Cyp2c11 substrate) were significantly changed by 1,25(OH)2D3 treatment in liver microsomes, but the kinetics of acetaminophen (an Ugt1a6/1a7/1a8 substrate) remained unaffected, consistent with Western blotting data for Ugt1a6. In rat pharmacokinetic studies, the total body clearance (CL) and nonrenal clearance (CLNR) of BUP were significantly reduced by 1,25(OH)2D3, but unexpectedly, the total area under the plasma concentration versus time curve from time zero to infinity (AUC) of hydroxybupropion (HBUP) was increased probably due to a marked reduction in the renal clearance (CLR) of HBUP. Additionally, the AUC, CL, and CLNR for TOL and the AUC for 4-hydroxytolbutamide (HTOL) were unaffected by 1,25(OH)2D3 in vivo. Discrepancies between observed in vitro metabolic activity and in vivo pharmacokinetics of TOL were possibly due to a greater apparent distribution volume at the steady-state (Vss) and lower plasma protein binding in 1,25(OH)2D3-treated rats. Our results suggest possible drug-drug and drug-nutrient interactions and provide additional information concerning safe drug combinations and dosing regimens for patients taking VDR ligand drugs including 1,25(OH)2D3.

Efficacy and safety of tanezumab administered as a fixed dosing regimen in patients with knee or hip osteoarthritis: a meta-analysis of randomized controlled phase III trials.

This study aims to evaluate the efficacy and safety of tanezumab administered as a fixed dosing regimen in patients with knee or hip osteoarthritis. Randomized controlled phase III trials (RCTs) that evaluated the efficacy and safety associated with tanezumab for knee or hip OA were systematically identified by searching electronic databases, including Cochrane Library, PubMed, and Embase, for 30 years from December 1990 up to July 2020. Ten relevant studies were included in our meta-analysis. The research was reported based on the preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure the reliability and verity of results. Our study showed that the tanezumab groups were more effective than the placebo groups in terms of mean change from the baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (P < .00001), WOMAC physical functional (P < .00001), and patient's global assessment (PGA) (P < .00001). Discontinued due to adverse events (AEs) (P < .00001), serious AEs (P = .02), abnormal peripheral sensations (both P < .00001), and peripheral neuropathy (P < .002) in tanezumab groups were significantly higher than that in control groups. Compared with placebo, tanezumab can effectively relieve pain and improve WOMAC physical function and patient's global assessment (PGA) in knee and hip osteoarthritis. Meanwhile, adverse events are transient in nature and generally well-tolerated. However, we still need large-sample, high-quality studies to investigate the long-term safety of tanezumab to give the conclusion.

Evaluation of characteristics and dosing regimens in patients with new or recurrent thrombosis on apixaban and rivaroxaban.

Direct factor Xa inhibitors, such as apixaban and rivaroxaban, are widely used for treatment and prevention of venous thromboembolism; however, recent cases of therapeutic failure have been reported. Potential risk factors associated with therapeutic failure such as dose deviations outside of package labeling recommendations, and the use of direct factor Xa-specific inhibitor levels to guide clinical decision making continue to be areas of further investigation. Our study aimed to describe characteristics and dosing regimens in patients on apixaban or rivaroxaban who experienced a new or recurrent thrombosis. We performed a retrospective chart review on 190 patients on either apixaban or rivaroxaban presenting to our institution with new or breakthrough thromboembolism. Evaluation of prescribed anticoagulation regimens compared to package labeling recommendations, direct factor Xa inhibitor-specific anti-Xa levels, anticoagulation interruptions, use of parenteral bridge anticoagulation, final anticoagulation regimen disposition, and thrombosis-associated mortality were recorded. In patients presenting with breakthrough thromboembolism, 78% were on a regimen that matched package labeling recommendations. Anti-Xa levels were documented in 66 patients, the majority of which fell within institutional expected ranges at time of thrombosis. Therapy interruptions immediately prior to thrombosis were observed in 22% of patients and 21% of those patients received parenteral anticoagulation during interruption. Upon discharge, 46% of patients continued the same anticoagulation regimen with no changes. The mortality rate was 6%. In patients who present with new thromboembolism on apixaban or rivaroxaban, a thorough review of risks and benefits should be conducted to mitigate future risk of recurrent thrombosis.

Results of decision support system implementation for prescribing anticoagulants to patients with atrial fibrillation in hospital

In 819% of patients with atrial fibrillation (AF) with anticoagulant therapy (ACT), hemorrhagic complications occur, including due to excess doses of AC. At the same time, ACT is necessary for patients with AF, since anticoagulants effectively reduces the risk of ischemic stroke. To make a decision on the appointment of ACT, it is necessary to correlate the risks of ischemic stroke and bleeding, this requires knowledge of current clinical using ACT recommendations and instructions. Among patients admitted to hospital, 30% receive ACT, so increasing adherence to clinical recommendations for prescribing AC to patients with AF by doctors of various profiles is an urgent task. To analyze the adherence of physicians to recommendations for prescribing ACT before and after the introduction of decision support system (DSS) in patients with AF in a multi-specialty hospital. A single-center non-randomized study with historical control to assess adherence to recommendations based on the analysis of medical prescriptions and the structure of drug errors in patients with AF in a multi-specialty hospital in Moscow before and after the introduction of DSS. Compliance with the recommendations of physicians was evaluated in the sections indications /contraindications to AC and dosage regimen of AC. The presence of deviations from the clinical recommendations /instructions for medical use of AC was regarded as management of the patient with non-compliance with recommendations. Physicians adherence level to recommendations was calculated as the ratio of cases of compliance with recommendations to the total number of cases. In the control and experimental groups, there was a significant increase in the proportion of POAC at discharge in comparison with admission to hospital: from 54.5 to 76.8% (p=0.0005) and from 63 to 85.7% (p=0.0002), respectively. However, only in the experimental group it was possible to significantly reduce the number of patients without a prescribed ACT (if there are indications) from 7.6 to 1% (p=0.04) in comparison with admission. During the study, it was possible to significantly increase physicians adherence level to the recommendations for the AC dosage regimen in patients with AF from 59% (44 discrepancies for 107 prescriptions) to 84.6% (16 discrepancies for 104 prescriptions); p0.005. Before the introduction of the DSS, the analysis of drug prescriptions revealed 56 drug errors (0.5 errors per patient), after the introduction of the DSS, the number of drug errors significantly decreased to 21 (0.2 errors per patient); p0.05. After the introduction of DSS, the number of sub-therapeutic doses of AC was reduced from 31 (27.7%) to 8 (7.6%); p0.05. The level of adherence to the recommendations for prescribing ACT to patients with AF in the hospital is high. The use of DSS increases the level of adherence to the recommendations on the AC dosage regimen in patients with AF, as well as eliminates errors in calculating the risk of ischemic stroke and systemic thromboembolic complications, and contributes to reducing the frequency of prescribing sub-therapeutic doses of AC.

Switching antiepileptic drugs to once-daily dosing regimens in epilepsy patients.

Antiepileptic drug (AED) non-adherence is an important factor contributing to poor seizure control in patients with epilepsy. The aim of this study is to investigate seizure improvement after switching AEDs to once-daily dosing regimens in patients with drug-resistant epilepsy related to AED non-adherence. We performed a 10-year retrospective analysis of drug-resistant epilepsy patients whom AED non-adherence attributed to drug resistance and switched AEDs to once-daily dosing regimens. Successful switching was defined by at least 70% reduction in seizure frequency without troublesome adverse events. Among 401 patients with drug-resistant epilepsy, 88 patients with AED non-adherence were switched to once-daily dosing regimens. Forty-six patients (52.3%) experienced successful seizure control following the switch. A higher chance of successful switch was found in patients without MRI abnormality (16/46 vs. 24/42; P=.04) and in patients who were switched to extended-release formulations or different AEDs with longer half-lives (33/46 vs. 19/42; P=.02). Our study shows that switching AEDs to once-daily dosing regimens was an effective therapeutic option in patients with poor seizure control related to AED non-adherence. Treatment with extended-release formulations or drugs with longer half-lives should be considered in these patients.

Optimization of tigecycline dosage regimen for different infections in the patients with hepatic or renal impairment

Objective The objective of this study was to investigate the cumulative fraction of response (CFR) of various tigecycline dosing regimens in patients with hepatic or renal impairment. Methods Monte Carlo simulations were performed using pharmacokinetic parameters and microbiological data to evaluate various tigecycline regimens in patients with hepatic or renal impairment. Results For HAP and cIAI, the regimen of 25 mg q12h achieved CFR values of >90% in Child-Pugh C patients against Gram-positive bacteria and partial Gram-negative bacteria (Escherichia coli and Klebsiella oxytoca). However, dose increases of tigecycline was mostly required for Enterobacter cloacae, Klebsiella pneumoniae and Acinetobacter baumanni. The conventional tigecycline regimen (50 mg q12h) was effective for HAP and cIAI caused by Gram-positive bacteria and Escherichia coli in patients with renal impairment. For HAP caused by Klebsiella pneumoniae and Enterobacter cloacae, patients with severe renal failure can use the standard dose regimen 50 mg q12h, and other patients need to increase the dose of tigecycline. However, when treating cSSSI caused by Acinetobacter baumannii, Enterobacter cloacae and Klebsiella pneumoniae, all tigecycline maintenance doses have a CFR <90%. Conclusions It is necessary to optimize tigecycline dosage regimens in patients with hepatic or renal impairment in order to maximise clinical response and minimise the probability of exposure-related toxicity.

Response to mepolizumab treatment is sustained across 4-weekly dosing periods.

BackgroundMepolizumab (100 mg delivered s.c. every 4 weeks) is indicated for add-on maintenance treatment for patients with severe eosinophilic asthma. Mepolizumab has been shown to reduce exacerbations and the requirement for daily oral corticosteroids, and improve asthma control and symptoms. However, data on the durability of the response to mepolizumab during dosing periods are limited. The aim of this study was to investigate the efficacy profile in patients with severe eosinophilic asthma over the 4-weekly dosing period for various fixed mepolizumab doses.MethodsThis was a post hoc analysis of data from the phase IIb/III DREAM study. Patients ≥12 years of age with severe eosinophilic asthma were randomised (1:1:1:1) to receive intravenous mepolizumab 75 mg (equivalent to 100 mg s.c.), 250 mg, 750 mg or placebo, plus standard of care, every 4 weeks for 52 weeks. The number of exacerbations and eDiary data (peak expiratory flow, rescue medication use and symptom scores) from two periods in each 4-weekly dosing interval (days 1–14 and 15–28) over the 52-week treatment period were analysed.FindingseDiary data and the proportion of patients experiencing ≥1 exacerbation were similar during the first and second 2 weeks of a dosing period across all mepolizumab doses.InterpretationThese results demonstrate that the response to mepolizumab is sustained over the 4-weekly dosing period with no differences across a 10-fold dose range and supports the use of the current mepolizumab dosing regimen in patients with severe eosinophilic asthma.

What is the best dosage regimen for patients who at first don't respond completely to ixekizumab?

What is the best dosage regimen for patients who at first don't respond completely to ixekizumab?

On the pharmacological evaluation of bisphosphonates in humans.

One of the key parameters for a successful treatment with any drug is the use of an optimal dose regimen. Bisphosphonates (BPs) have been in clinical use for over five decades and during this period clinical pharmacokinetic (PK) and pharmacodynamic (PD) evaluations have been instrumental for the identification of optimal dose regimens in patients. Ideal clinical PK and PD studies help drug developers explain variability in responses and enable the identification of a dose regimen with an optimal effect. PK and PD studies of the unique and rather complex pharmacological properties of BPs also help determine to a significant extent ideal dosing for these drugs. Clinical PK and PD evaluations of BPs preferably use study designs and assays that enable the assessment of both short- (days) and long-term (years) presence and effect of these drugs in patients. BPs are mainly used for metabolic bone diseases because they inhibit osteoclast-mediated bone resorption and the best way to quantify their effects in humans is therefore by measuring biochemical markers of bone resorption in serum and urine. In these very same samples BP concentrations can also be measured. Short-term serum and urine data after both intravenous (IV) and oral administration enable the assessment of oral bioavailability as well as the amount of BP delivered to the skeleton. Longer-term data provide information on the anti-resorptive effect as well as the elimination of the BP from the skeleton. Using PK-PD models to mathematically link the anti-resorptive action of the BPs to the amount of BP at the skeleton provides a mechanism-based explanation of the pattern of bone resorption during treatment. These models have been used successfully during the clinical development of BPs. Newer versions of such models, which include systems pharmacology and disease progression models, are more comprehensive and include additional PD parameters such as BMD and fracture risk. Clinical PK and PD studies of BPs have been useful for the identification of optimal dose regimens for metabolic bone diseases. These analyses will also continue to be important for newer research directions, such as BP use in the delivery of other drugs to the bone to better treat bone metastases and bone infections, as well as the potential benefit of BPs at non-skeletal targets for the prevention and treatments of soft tissue cancers, various fibroses, and other cardiovascular and neurodegenerative diseases,andreduction in mortality and extension of lifespan.

Chloroquine dosage regimens in patients with COVID-19: Safety risks and optimization using simulations

Currently no specific medicinal treatment exists against the new SARS-CoV2 and chloroquine is widely used, since it can decrease the length of hospital stay and improve the evolution of the associated COVID-19 pneumonia. However, several safety concerns have been raised from chloroquine use due to the lack of essential information regarding its dosing. The aim of this study is to provide a critical appraisal of the safety information regarding chloroquine treatment and to apply simulation techniques to unveil relationships between the observed serious adverse events and overdosing, as well as to propose optimized dosage regimens. The dose related adverse events of chloroquine are unveiled and maximum tolerated doses and concentration levels are quoted. Among others, treatment with chloroquine can lead to severe adverse effects like prolongation of the QT interval and cardiomyopathy. In case of chloroquine overdosing, conditions similar to those produced by SARS-CoV2, such as pulmonary oedema with respiratory insufficiency and circulatory collapse, can be observed. Co-administration of chloroquine with other drugs for the treatment of COVID-19 patients, like azithromycin, can further increase the risk of QT prolongation and cardiomyopathy. For elder patients there is a high risk for toxicity and dose reduction should be made. This study unveils the risks of some widely used dosing regimens and binds the observed serious adverse events with dosing. Based on simulations, safer alternative dosage regimens are proposed and recommendations regarding chloroquine dosing are made.

Dose Optimization of Cefpirome Based on Population Pharmacokinetics and Target Attainment during Extracorporeal Membrane Oxygenation.

To obtain the optimal dosage regimen in patients receiving extracorporeal membrane oxygenation (ECMO), we developed a population pharmacokinetics model for cefpirome and performed pharmacodynamic analyses. This prospective study included 15 patients treated with cefpirome during ECMO. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF) at predose and 0.5 to 1, 2 to 3, 4 to 6, 8 to 10, and 12 h after cefpirome administration. The population pharmacokinetic model was developed using nonlinear mixed effects modeling and stepwise covariate modeling. Monte Carlo simulation was used to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) according to the MIC distribution. Cefpirome pharmacokinetics were best described by a two-compartment model. Covariate analysis indicated that serum creatinine concentration (SCr) was negatively correlated with clearance, and the presence of ECMO increased clearance and the central volume of distribution. The simulations showed that patients with low SCr during ECMO-ON had lower PTA than patients with high SCr during ECMO-OFF; so, a higher dosage of cefpirome was required. Cefpirome of 2 g every 8 h for intravenous bolus injection or 2 g every 12 h for extended infusion over 4 h was recommended with normal kidney function receiving ECMO. We established a population pharmacokinetic model for cefpirome in patients with ECMO, and appropriate cefpirome dosage regimens were recommended. The impact of ECMO could be due to the change in patient status on consideration of the small population and uncertainty in covariate relationships. Dose optimization of cefpirome may improve treatment success and survival in patients receiving ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.).

Amikacin nomogram for treatment of adult cystic fibrosis exacerbations based on an external evaluation of a population pharmacokinetic model.

In patients with cystic fibrosis (CF), amikacin is the alternative for the treatment of acute pulmonary exacerbations associated with pathogens resistant to tobramycin. Population pharmacokinetic (PK) models of amikacin in adult patients with CF have been previously published. However, current dosing recommendations remain disputed (Illamola et al. Clin Pharmacokinet. 2018;57(10):1217-1228). We perform here the first external evaluation of a published amikacin adult CF population PK model and propose a dosing nomogram for initial dosing. We retrospectively collected demographic, biological, and clinical data from the medical records of adult patients who had received intravenous amikacin. To assess the predictive performance of this model we applied visual comparison of predictions to observations, calculation of bias and inaccuracy, and simulation-based diagnostics. Monte Carlo simulations from the evaluated model were used to compare maximum concentration/minimum inhibitory concentration achieved with different dosing regimens. A total of 91 concentrations from 19 adult patients with CF were collected for external evaluation. The model predicted amikacin concentrations with reasonable bias (7.2% [95% confidence interval, CI: -0.7% to 15.0%]) and inaccuracy (18.2% [95% CI: 12.0%-24.4%]). Our simulations with this model suggest that administered amikacin doses must be adjusted to creatinine clearance and also adjusted to body weight (doses from 20 to 45 mg/kg/d). According to these simulations, we developed the Montreal amikacin nomogram to optimize amikacin dosing regimens in patients with CF. In conclusion, we developed the first nomogram to optimize initial amikacin dosing regimens in patients with CF based on this external evaluation of a recently published amikacin population PK model.

Model-Informed Artificial Intelligence: Reinforcement Learning for Precision Dosing.

The availability of multidimensional data together with the development of modern techniques for data analysis represent an exceptional opportunity for clinical pharmacology. Data science-defined in this special issue as the novel approaches to the collection, aggregation, and analysis of data-can significantly contribute to characterize drug-response variability at the individual level, thus enabling clinical pharmacology to become a critical contributor to personalized healthcare through precision dosing. We propose a minireview of methodologies for achieving precision dosing with a focus on an artificial intelligence technique called reinforcement learning, which is currently used for individualizing dosing regimen in patients with life-threatening diseases. We highlight the interplay of such techniques with conventional pharmacokinetic/pharmacodynamic approaches and discuss applicability in drug research and early development.

Comparison of daily dosing versus Monday through Friday dosing of vismodegib for locally advanced basal cell carcinoma and basal cell nevus syndrome: A retrospective case series

Comparison of daily dosing versus Monday through Friday dosing of vismodegib for locally advanced basal cell carcinoma and basal cell nevus syndrome: A retrospective case series

Are We Missing Treatment Standards for Thromboprophylaxis of the Obese and Super-Obese Patient Population? A Prospective Systematic Cohort Study.

Venous thromboembolism (VTE) is the most frequent 30-day complication in patients with morbid obesity undergoing bariatric surgery. Therefore, there is a need for optimized low molecular weight heparin (LMWH) thromboprophylaxis dosing strategies in order to avoid VTE-associated morbidity and mortality in this patient population. The primary goal was to evaluate if a pre-specified enoxaparin dosing regimen in patients undergoing bariatric surgery reaches anti-factor Xa (aFXa) levels in the defined target range (0.2-0.4U/ml). Second, we aimed to identify biometric and laboratory parameters that might influence the aFXa value. A prospective database of 236 patients with obesity who received thromboprophylaxis with enoxaparin was established. These patients were divided into two weight-adjusted groups (group 1 < 150kg, group 2 ≥ 150kg). Enoxaparin was administered twice daily; dosing was determined by weight (group 1, 2 × 40mg/day; group 2, 2 × 60mg/day). In both groups, the peak aFXa serum level was evaluated 3days after initiating the thromboprophylaxis. In group 1 (body mass index (BMI) 42.94 ± 6.84kg/m2, weight of 121.7 ± 17.49kg), seventy-one of the included 124 patients (57.25%) reached the aFXa target range of 0.2 to 0.4U/m. In group 2 (BMI 63.21 ± 10.05kg/m2, weight of 191.66 ± 33.37kg), 68 of 112 (60.71%) patients scored prophylactic aFXa range. Multiple regression of the biometric and laboratory parameters showed significance for weight, waist-to-hip ratio, glomerular filtration rate (GFR), creatinine, and HbA1c exclusively in group 1. There was no case of VTE within 3months after surgery and no case of severe perioperative bleeding in those patients who underwent surgery. Measurement of the aFXa level helps to define the real prophylactic thromboprophylaxis status in patients with obesity, especially in those with a weight above 150kg. In patients at risk, the measurement of aFXa should be considered in routine clinical practice.