Plasma trough concentration distribution and safety of high‐dose teicoplanin for patients with augmented renal clearance

alexandrossfakianakis shared this article with you from Inoreader Plasma trough concentration distribution and safety of high‐dose teicoplanin for patients with augmented renal clearance via Journal of Clinical Pharmacy and Therapeutics Teicoplanin plasma trough concentration (C min) and probability rates of C min > 10 mg/L in the augmented renal clearance (ARC) and non-ARC groups on the third day of medication (day 3) and during the dose maintenance period. After the HD, plasma samples were collected before the third day of medication. The teicoplanin C min values in the ARC and non-ARC groups were 17.3 ± 9.2 mg/L and 15.5 ± 7.9 mg/L, respectively (p = 0.663) (Figure A). The probability rate of C min > 10 mg/L also did not differ significantly between the two groups (85.7% [6/7] vs. 60.0% [6/10], p = 0.338, Figure C). During the dose maintenance period (3 days after medication), the teicoplanin C min was significantly lower in ARC group than in the non-ARC group (18.3 ± 5.1 mg/L vs. 25.5 ± 11.9 mg/L, p = 0.016, Figure A), while there was no significant difference in the probability rate of C min > 10 mg/L between the two groups (90.0% [9/10] vs. 96.2% [25/26], p = 0.484, Figure C). After the LD, plasma samples were collected before the third day of medication. The teicoplanin C min values in the ARC and non-ARC groups were 6.8 ± 3.9 mg/L and 7.9 ± 3.1 mg/L, respectively (p = 0.585) (Figure B). The probability rate of C min > 10 mg/L did not differ significantly between the two groups (20.0% [1/5] vs. 11.1% [1/9], p = 1.000, Figure D). During the dose maintenance period, the teicoplanin C min values in the ARC and non-ARC groups were 12.2 ± 6.3 mg/L and 13.0 ± 4.6 mg/L, respectively (p = 0.713) (Figure B). The probability rate of C min > 10 mg/L was 61.5% (8/13) in both groups (Figure D). It should be noted that on the third day of medication, the HD group had a significantly higher teicoplanin C min than the LD group for ARC (17.3 ± 9.2 mg/L vs. 6.8 ± 3.9 mg/L, p = 0.039, Figure A and B), but there was no significant intergroup difference in the probability rates of C min > 10 mg/L (85.7% [6/7] vs. 20.0% [1/5], p = 0.072, Figures C and D). During the dose maintenance period, the teicoplanin C min was significantly higher in the HD group than in the LD group for ARC (18.3 ± 5.1 mg/L vs. 12.2 ± 6.3 mg/L, p = 0.022, Figures A and B), while there was no significant intergroup difference in their probability rates of C min > 10 mg/L (90.0% [9/10] vs. 61.5% [8/13], p = 0.179, Figures C and D). Notes: A, HD; B, LD; C, HD; D, LD; *p < 0.05. Abstract What Is Known and Objective There are few reports on the distribution of the plasma trough concentration (C min) of teicoplanin in patients with augmented renal clearance (ARC) and on the safety of a high-dose regimen (HD; 800 mg loading dose for q12h three times followed by an 800 mg qd maintenance dose). The objective of this study was to determine the C min values of teicoplanin in ARC patients using HD teicoplanin to provide a reference for individualized medication. Methods Data on patients treated with teicoplanin from January 2019 to January 2021 were collected retrospectively and divided into ARC (creatinine clearance rate [CCr] >130 ml/min, n = 22) and non-ARC (60 ml/min ≤ CCr ≤130 ml/min, n = 24) groups. The C min values in the two patient groups were analysed during the HD and the low-dose regimen (LD; all other regimens) on the third day of medication and during the dose maintenance period. Liver and kidney function indexes were also analysed before and after medication. Results and Discussions On the third day of the HD, C min did not differ significantly between the ARC and non-ARC groups (17.3 ± 9.2 mg/L [mean ± SD] vs. 15.5 ± 7.9 mg/L, p = 0.663), while C min in the ARC group was significantly lower for the LD (6.8 ± 3.9 mg/L, p = 0.039). During the dose maintenance period, C min in the ARC group when receiving the HD (18.3 ± 5.1 mg/L) was significantly lower than that in the non-ARC group (25.5 ± 11.9 mg/L, p = 0.016) and significantly higher than that for the LD (12.2 ± 6.3 mg/L, p = 0.022). Nephrotoxicity and hepatotoxicity incidence rates did not differ significantly between these groups. What Is New and Conclusion These results suggest that it is necessary to apply a loading dose of 800 mg (but not higher) q12h three times for patients with ARC, with 800 mg needed as a maintenance dose during severe infection, and 600 mg or 400 mg for mild infection. View on Web

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Validation of the Augmented Renal Clearance in Trauma Intensive Care scoring system for augmented renal clearance prediction in a trauma subgroup of a mixed ICU population

alexandrossfakianakis shared this article with you from Inoreader Validation of the Augmented Renal Clearance in Trauma Intensive Care scoring system for augmented renal clearance prediction in a trauma subgroup of a mixed ICU population via Journal of Clinical Pharmacy and Therapeutics (Left) ROC curves for ARC detection in trauma subgroup: comparison between ARCTIC score ROC curve and regression ROC curve. AUC, area under the curve; CI, confidence interval. (Right) ROC curves for ARC detection in medical/surgical subgroup: comparison between ARCTIC score ROC curve and regression ROC curve. Abstract What is known and Objective Augmented renal clearance is prevalent in trauma patients and leads to subtherapeutic levels of renally eliminated medications with potentially unfavourable clinical outcomes. The Augmented Renal Clearance of Trauma in Intensive Care (ARCTIC) score has been developed to predict augmented renal clearance in critically ill trauma patients. Our primary objective was to validate this score among the trauma subgroup of a mixed intensive care patient cohort. Methods This single-centre, retrospective, observational cohort study assessed augmented renal clearance using a timed 24-h urine collection performed weekly. ARC was defined as a measured creatinine clearance of ≥130 ml/min/1.73 m2. ARCTIC score performance was evaluated through a receiver operator characteristic curves and analysis of sensitivities and specificities for the trauma subgroup, the medical/surgical subgroup and the pooled cohort. Results and Discussion Augmented renal clearance was observed in 33.9% (n = 58) of trauma patients (n = 171) and 15.7% (n = 24) of medical/surgical patients (n = 153). Examination of different cutoffs for the ARCTIC score in our trauma population confirmed that the optimal cutoff score was ≥6. Comparison between ROC curves for ARCTIC score and for regression model based upon our data in trauma patients indicated validation of the score in this subgroup. Comparison of sensitivities and specificities for ARCTIC score between trauma (93.1% and 41.6%, respectively) and medical/surgical subjects (87.5% and 49.6%, respectively) showed no clinical nor statistical difference, suggesting validation for the medical/surgical subgroup as well. What is new and Conclusion In our mixed ICU population, the ARCTIC score was validated in the trauma subgroup. We also found that the score performed well in the medical/surgical population. Future studies should assess the performance of the ARCTIC score prospectively. View on Web

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3D Reconstruction of Phonatory Glottal Shape and Volume: Effects of Neuromuscular Activation

alexandrossfakianakis shared this article with you from Inoreader 3D Reconstruction of Phonatory Glottal Shape and Volume: Effects of Neuromuscular Activation via The Laryngoscope In this study, we utilized a 3D reconstruction approach to visualize the vocal fold medial surface during phonation in an in vivo canine hemilarynx, and we obtained direct measurements of glottal movement, and glottal volume waveform, and resulting voice quality. We present the glottal volume waveform as a correlate of laryngeal vibratory dynamics and highlight the importance of intrinsic laryngeal muscles in modulating medial surface dynamics to achieve improved voice quality. Introduction Although phonatory glottal posture and airflow pulse shape affect voice quality, studies to date have been limited by visualization of vocal fold (VF) vibration from a superior view. We performed a 3D reconstruction of VF vibratory motion during phonation from a medial view and assessed the glottal volume waveform and resulting acoustics as a function of neuromuscular stimulation. Study Design In vivo canine hemilarynx phonation. Methods Across 121 unique combinations of the superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN) stimulation, the hemilarynx was excited to the oscillation with airflow. VF medial surface reference points were tracked on high-speed video, mapped into 3D space, and surface shape was restored using cubic spline interpolation. Glottal surface shape, reconstruction-based parameters, and glottal volume waveform were calculated. Fundamental frequency (F0), cepstral peak prominence (CPP), and harmonic amplitude (H1-H2) were measured from high-quality audio samples. Results The glottis was convergent during opening and divergent during closing. Neuromuscular activation changed phonatory glottal shape and reduced glottal volume. Significant reduction in glottal volume and closing quotient were present with SLN stimulation. RLN stimulation significantly increased F0 and CPP and decreased H1-H2 (constricted glottis), while SLN effects were similar and synergistic with concurrent RLN stimulation. Conclusion 3D reconstruction of in vivo medial surface vibration revealed effects of laryngeal nerve stimulation on glottal vibratory pattern and acoustic correlates of voice quality. SLN activation resulted in significantly quicker glottal closure per cycle, decreased glottal volume, and higher-pitched, less breathy, and less noisy voice. RLN had a similar effect on acoustic measures. Level of Evidence N/A, Basic Science Laryngoscope, 2022 View on Web

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Could the Audiometric Criteria for Sudden Sensorineural Hearing Loss Miss Vestibular Schwannomas?

alexandrossfakianakis shared this article with you from Inoreader Could the Audiometric Criteria for Sudden Sensorineural Hearing Loss Miss Vestibular Schwannomas? via The Laryngoscope Patients with sudden hearing loss whose audiograms did not meet the formal audiometric criteria for sudden sensorineural hearing loss were found to have a similar rate of vestibular schwannoma as those who did. Therefore, we advocate a high index of suspicion of a concomitant vestibular schwannoma with sudden hearing loss of any severity, and urge our colleagues to consider referring those patients to an MRI scan regardless of the hearing loss severity. Objective To investigate the likelihood of missing a vestibular schwannoma (VS) diagnosis in patients who present with a sudden hearing loss (SHL) that does not meet the most accepted audiometric criteria for sudden sensorineural hearing loss (SSNHL) (a decrease of ≥30 dB at three consecutive frequencies). Methods All adult patients (>18 years) diagnosed with SHL of any severity in a tertiary care referral medical center between 2015 and 2020 and who underwent an MRI scan to rule out VS were included. Statistical analyses were conducted to evaluate the difference between the rate of VS among patients with an initial audiogram, which met the abovementioned criteria, and those who did not. Other audiometric criteria for SNHL were also evaluated (≥10 dB at ≥2 frequencies and ≥ 15 dB at one frequency). Results Of the 332 patients included in the study, 152 met the audiometric criteria for SSNHL, and 180 did not. Both groups had a similar VS rate (8.6% vs. 8.9%, p = 0.914). Similar results were found when other audiometric criteria for asymmetric SNHL were analyzed. In a subgroup analysis of patients with VS-associated SSNHL, neither the tumor size nor the Koos classification was associated with any of the audiometric criteria systems. Conclusion There should be a high index of suspicion for the presence of VS in patients with an SHL of any severity. Level of Evidence 3 Laryngoscope, 2022 View on Web

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Translating core intervention strategies into action: Interpersonal validation among selfinjuring adolescents and their mothers

alexandrossfakianakis shared this article with you from Inoreader Translating core intervention strategies into action: Interpersonal validation among selfinjuring adolescents and their mothers via Journal of Clinical Psychology Abstract Introduction Most evidence-supported treatments for psychiatric problems teach clients skills to incorporate into their daily lives. Yet little research rigorously examines the extent to which individuals absorb these strategies and can competently apply them outside of the therapeutic relationship. Objectives The current study examined the degree to which selfinjuring adolescents and their mothers (n = 30 dyads) and typical control mother–daughter dyads (n = 30) were able to utilize a multicomponent interpersonal validation-oriented skill from dialectical behavior therapy, after a single teaching. We also aimed to assess whether variance in Gentle, Interested, Validate, and Easy (GIVE) skill practice was associated with a physiological index of emotion regulation (respiratory sinus arrhythmia [RSA]). Method An observational coding system was developed to measure skill-related behavior across four key domains (be[ing] gentle, act[ing] interested, validation, and us[ing] an easy manner; GIVE) and applied during two family conflict discussions (pre- and postskills training). Mother and adolescent RSA data were collected at rest and across discussion tasks. Results Behavioral indicators of skill use improved pre-to-post skills training across the entire sample, except in one GIVE domain (easy manner). Selfinjuring youth and their mothers demonstrated greater improvements than control dyads with respect to being gentle. RSA reactivity scores predicted behavioral validation, such that higher RSA was associated with higher validation scores. Conclusions As a field, we currently have a limited understanding of how intervention skills are used, and what factors predict effective skill application. Results suggest selfinjuring adolescents and their mothers can learn and improve on most aspects of a core intervention strategy after a single teaching and that better physiological regulation during conflict is associated with more validating behaviors. View on Web

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Serum Neutralizing Antibody Titers 12 months after COVID-19 mRNA Vaccination:

alexandrossfakianakis shared this article with you from Inoreader Serum Neutralizing Antibody Titers 12 months after COVID-19 mRNA Vaccination: Correlation to Clinical Variables in an Adult, US-Population via Clinical Infectious Diseases Advance Access Abstract Background We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population. Methods Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively. Results After completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naïve individuals (18-fold increase) and increased in prior COVID-19 + individuals (132-fold increase). Age >65 years (β=-0.94, p = 0.001) and malignancy (β=-0.88, p = 0.002) reduced strength of response at 1 month. Both neutralization strength and durability at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1.10, p = 0.004); (β=-0.66, p = 0.014)], diabetes mellitus [(β=-0.57, p = 0.032); (β=-0.44, p = 0.028)], and systemic steroid use [(β=-0.066, p = 0.032); (β=-0.55, p = 0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2. Post-booster neutralization increased with prior COVID-19 (β = 2.9, p-value < 0.0001), and malignancy reduced neutralization response (β=-0.68, p = 0.03), regardless of infection status. Conclusion Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Malignancy was associated with lower booster-dose response regardless of prior COVID infection, suggesting a need for clinically guided vaccine regimens. View on Web

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Humoral immune response to authentic circulating SARS‐CoV‐2 variants elicited by booster vaccination with distinct RBD subunits in mice

alexandrossfakianakis shared this article with you from Inoreader Humoral immune response to authentic circulating SARS‐CoV‐2 variants elicited by booster vaccination with distinct RBD subunits in mice via Journal of Medical Virology Abstract SARS-CoV-2 variants could induce immune escape by mutations of the spike protein which are threatening to weaken vaccine efficacy. A booster vaccination is expected to increase the humoral immune response against SARS-CoV-2 variants in the population. We showed that immunization with two doses of wild type receptor-binding domain (RBD) protein, and booster vaccination with wild type or variant RBD protein all significantly increased binding and neutralizing antibody titers against wild type SARS-CoV-2 and its variants in mice. Only the booster immunization by Omicron (BA.1)RBD induced a strong antibody titer against the omicron virus strain and comparable antibody titers against all the other virus strains. These findings might shed the light on COVID-19 booster immunogens. This article is protected by copyright. All rights reserved. View on Web

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