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Πέμπτη 24 Νοεμβρίου 2022

Prevalence, Distribution, and Characteristics Associated with Possession of Buprenorphine Waiver

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Persons with opioid use disorder (OUD) may present with infectious complications from injection drug use, thus ID physicians are uniquely positioned to treat OUD. Buprenorphine is safe and effective for OUD but remains underutilized. The prevalence and geographic distribution of ID physicians who are waivered to prescribe buprenorphine are unknown.
Methods
This cross-sectional study merged data from several publicly available datasets from November 1, 2021 to January 15, 2022. Our primary outcome was proportion of ID physicians possessing buprenorphine waivers in the United States. We identified individual and county-level characteristics associated with buprenorphine waiver possession. We then used geospatial analysis to determine geographic distribution of waivered ID physicians.
Results
We identified 6372 ID physicians in the US, among whom 170 (2.7%) possessed waivers. Most ID physicians (97.3%) practice d in metropolitan counties. In our multivariable analysis, ID physicians had lower odds of having a waiver for every 10-year increase since graduating medical school (OR 0.79, 95% CI 0.68-0.91). ID physicians practicing in counties with higher proportion of uninsured residents had lower odds of having a waiver (OR 0.75, 95% CI 0.62-0.90). Among counties with at least one ID physician (n = 729), only 11.2% had at least one waivered ID physician.
Conclusions
We found an extremely low prevalence and skewed geographic distribution of ID physicians with buprenorphine waivers. Our findings suggest an urgent need to increase the workforce of ID physicians waivered to prescribe buprenorphine and a call for increased integration of OUD education into ID training and continuing medical education.
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Optimal exposure to docetaxel in adjuvant chemotherapy for early‐stage breast cancer

alexandrossfakianakis shared this article with you from Inoreader
Optimal exposure to docetaxel in adjuvant chemotherapy for early-stage breast cancer

Among the 70 participants, 47 (67.1%) developed severe neutropenia. The PopPK analysis showed that the typical drug clearance (CL) rate was 37.4 L/h. Age was a significant covariate of CL rate, and aspartate aminotransferase and albumin levels were covariables of the volume of distribution. The AUC estimated using the maximum a posteriori Bayesian method can predict the toxicity of docetaxel in patients with breast cancer. Docetaxel AUC >3.0 mg h/L, platinum and baseline haemoglobin level are risk factors for docetaxel-induced grade 3/4 neutropenia. The AUC of first cycle may not predict the occurrence rates of grade 3/4 neutropenia in later cycles.


Abstract

What Is Known and Objective

Drug-induced neutropenia is the main reason for the dose limitation of docetaxel in patients with breast cancer. The area under the drug concentration-time curve (AUC) of docetaxel is associated with neutropenia. However, the optimal exposure to docetaxel for receiving postoperative adjuvant chemotherapy remains unclear. Therefore, we aimed to evaluate the relationship between the docetaxel AUC and neutropenia, identify potential influencing factors, and explore the best monitoring target for docetaxel when treating patients with early-stage breast cancer using a population pharmacokinetic (PopPK) model.

Methods

Docetaxel plasma concentration, demographics, clinical data, and related laboratory data were collected. PopPK analyses were performed using a nonlinear mixed-effect modelling program. The docetaxel AUC was determined using the maximum a posteriori Bayesian (MAPB) method. The docetaxel exposure-toxicity threshold measured from the AUC for neutropenia was determined using the receiver operating characteristic (ROC) curve. The correlation between docetaxel exposure and neutropenia was analysed using multivariable logistic regression.

Results

Among the 70 participants, 47 (67.1%) developed severe neutropenia. The PopPK analysis showed that the typical drug clearance (CL) rate was 37.4 L/h. Age was a significant covariate of CL rate, and aspartate aminotransferase and albumin levels were covariables of the volume of distribution. The multivariable regression analysis showed that AUC >3.0 mg.h/L (odds ratio [OR], 5.940; 95% confidence interval [CI], 1.693–20.843; P = 0.005), platinum use (OR, 0.156; 95% CI, 0.043–0.562; P = 0.005) and baseline haemoglobin level (OR, 0.938; 95% CI, 0.887–0.993; P = 0.027) were significant factors influencing the occurrence of grade 3/4 neutropenia. The AUC of first cycle may not predict the occurrence rates of grade 3/4 neutropenia in later cycles.

What Is New and Conclusion

We developed a docetaxel PopPK model for patients with early-stage breast cancer. Age and AST and ALB levels were significant covariates. AUC estimated using the MAPB method can predict the toxicity of docetaxel in patients with breast cancer. Docetaxel AUC >3.0 mg.h/L, absence of platinum use and low baseline haemoglobin level were risk factors for docetaxel-induced grade 3/4 neutropenia.

Study Registration

Chinese Clinical Trial Center Registry (ChiCTR2200056460).

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Impact of maximal extent of resection on postoperative deficits, patient functioning and survival within clinically important glioblastoma subgroups

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
The impact of extent of resection (EOR), residual tumor volume (RTV), and gross-total resection (GTR) in glioblastoma subgroups is currently unknown. This study aimed to analyze their impact in patient subgroups in relation to neurological and functional outcomes.
Methods
Patients with tumor resection for eloquent glioblastoma between 2010 and 2020 at four tertiary centers were recruited from a cohort of 3919 patients.
Results
One thousand and forty-seven (1047) patients were included. Higher EOR and lower RTV were significantly associated with improved OS and PFS across all subgroups, but RTV was a stronger prognostic factor. GTR based on RTV improved median OS in the overall cohort (19.0 months, p<0.0001), and in the subgroups with IDH wildtype tumors (18.5 months, p=0.00055), MGMT methylated tumors (35.0 months, p<0.0001), aged <70 (20.0 months, p<0.0001 ), NIHSS 0-1 (19.0 months, p=0.0038), KPS 90-100 (19.5 months, p=0.0012), and KPS ≤ 80 (17.0 months, p=0.036). GTR was significantly associated with improved OS in the overall cohort (HR 0.58, p=0.0070) and improved PFS in the NIHSS 0-1 subgroup (HR 0.47, p=0.012). GTR combined with preservation of neurological function (OFO 1 grade) yielded the longest survival times (median OS 22.0 months, p <0.0001), which was significantly more frequently achieved in the awake mapping group (50.0%) than in the asleep group (21.8%) (p<0.0001).
Conclusions
Maximum resection was especially beneficial in the subgroups aged <70, NIHSS 0-1, and KPS 90-100 without increasing the risk of postoperative NIHSS or KPS worsening. These findings may assist surgical decision making in individual glioblastoma patients.
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Predictive effect of pretreatment nutritional risk and GLIM‐defined malnutrition on the nutrition impact symptom clusters in patients with head and neck cancer undergoing radiotherapy

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Evidence supporting predictive effects of pretreatment nutritional risk and nutritional status on nutrition impact symptom (NIS) clusters during radiotherapy in patients with head and neck cancer (HNC) is insufficient.

Methods

At baseline (T1), we collected severity and interference of NIS (Head and Neck Patient Symptom Checklist), nutritional risk, and nutritional status. During (T2) and at the end of radiotherapy (T3), we re-evaluated NIS. Symptom clusters were identified by exploratory factor analysis using mean scores of NIS severity at T2 and T3. Predictive effects were explored by generalized estimating equations.

Results

Five hundred thirty-seven patients were recruited and 334 of them completed. Four clusters were identified; the oropharyngeal symptom cluster was the most severe and had the greatest interference with diet. Patients with pretreatment nutritional risk or malnutrition experienced more severe oropharyngeal symptom cluster.

Conclusions

Pretreatment nutritional risk or malnutrition could predict the oropharyngeal symptom cluster in patients with HNC undergoing radiotherapy.

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