Optimal Trough Concentration of Teicoplanin in Febrile Neutropenic Patients with Hematological Malignancy

Background: Teicoplanin is a glycopeptide antibiotic currently used for the treatment of methicillin-resistant Staphylococcus aureus. The need for therapeutic drug monitoring of teicoplanin has been increasingly highlighted as important. It is generally accepted that whereas a plasma trough concentration (Cmin) of ≥10 mg/L is appropriate for the majority of infections, it should exceed 20 mg/L for severe infections. The target Cmin of teicoplanin in patients with febrile neutropenia (FN) has not been reported. The aim of this study was to estimate the target Cmin for the treatment of FN in patients with hematological malignancy. Methods: In this retrospective, single-center, observational cohort study, the records of 52 hospitalized patients with hematological malignancy who were treated with teicoplanin for FN due to bacteriologically documented or presumptive gram-positive infections were analyzed. Results: A significant difference in the first Cmin of teicoplanin was observed between the response and nonresponse groups in patients with bacteremia. The areas under the receiver operating characteristic curves were 0.80 for clinical efficacy. The cut-off value of teicoplanin Cmin on days 4-6 was 15.2 mg/L (sensitivity 80.0%, specificity 75.0%). Conclusions: The authors propose a target teicoplanin Cmin of ≥15.2 mg/L for FN in patients with hematological malignancy.

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Transperineal ultrasound to estimate the appropriate ring pessary size for women with pelvic organ prolapse

International Urogynecology Journal ◽

10.1007/s00192-021-04975-9 ◽

2021 ◽

Author(s):

Claudia Manzini ◽

Mariëlla I. J. Withagen ◽

Frieda van den Noort ◽

Anique T. M. Grob ◽

Carl H van der Vaart

Keyword(s):

Pelvic Organ Prolapse ◽

Operating Characteristic ◽

Pelvic Organ ◽

Transperineal Ultrasound ◽

Small Ring ◽

Receiver Operating Characteristic Curves ◽

Ring Pessary ◽

Hiatal Area ◽

Significant Difference ◽

Control Study

Abstract Introduction and hypothesis The objective was to predict the successful ring pessary size based on the levator hiatal area (HA). Methods This is a prospective case–control study. Women with symptomatic pelvic organ prolapse (POP) choosing pessary treatment were included. All women underwent an interview, clinical examination, and 3D/4D transperineal ultrasound (TPUS). The ring pessary size used in each trial and the reason for unsuccessful trials were recorded. In addition, levator hiatal area divided by ring pessary size (HARP ratio) was measured at rest, maximum contraction, and maximum Valsalva. The HARP ratios of successful and unsuccessful trials were compared, receiver operating characteristic curves in the prediction of successful trials were constructed, and the cut-off optimizing sensitivity and specificity was identified. Results A total of 162 women were assessed and 106 were included with 77 successful trials, 49 unsuccessful trials owing to dislodgment or failure to relieve POP symptoms, and 20 unsuccessful trials owing to pain/discomfort. Rest HARP ratio and Valsalva HARP ratio were significantly smaller in the successful trials versus dislodgment/failure to relieve POP symptoms trials (mean rest HARP ratio [SD]: 2.93 [0.59] vs 3.24 [0.67], p = 0.021; median Valsalva HARP ratio (IQR): 4.65 (1.56) vs 5.32 (2.08), p = 0.004). No significant difference was observed between pain/discomfort trials and successful trials. The best cut-off for the prediction of successful trials was Valsalva HARP ratio ≤ 5.00. Conclusions Unsuccessful fitting trials due to dislodgment/failure to relieve POP symptoms are associated with a small ring pessary with respect to the levator HA. A ring pessary that produces a Valsalva HARP ratio > 5.00 has a higher risk of dislodgment/failure to relieve POP symptoms.

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Predictors of Voriconazole Trough Concentrations in Patients with Child–Pugh Class C Cirrhosis: A Prospective Study

Antibiotics ◽

10.3390/antibiotics10091130 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1130

Author(s):

Yichang Zhao ◽

Jingjing Hou ◽

Yiwen Xiao ◽

Feng Wang ◽

Bikui Zhang ◽

...

Keyword(s):

Trough Concentration ◽

Multiple Linear Regression Model ◽

Therapeutic Drug ◽

Time Activity ◽

Bivariate Correlation ◽

Significant Difference ◽

Daily Dose ◽

Pugh Class ◽

Trough Concentrations ◽

Class C

This prospective observational study aimed to clinically describe voriconazole administrations and trough concentrations in patients with Child–Pugh class C and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child–Pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentrations later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (p = 0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor <5), implying that CYP2C19 testing makes sense for precision medicine of Child–Pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R2 = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child–Pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.

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Expression Analysis of Protein Inhibitor of Activated STAT in Inflammatory Demyelinating Polyradiculoneuropathy

Frontiers in Immunology ◽

10.3389/fimmu.2021.659038 ◽

2021 ◽

Vol 12 ◽

Author(s):

Soudeh Ghafouri-Fard ◽

Bashdar Mahmud Hussen ◽

Fwad Nicknafs ◽

Naghme Nazer ◽

Arezou Sayad ◽

...

Keyword(s):

Immune Responses ◽

Operating Characteristic ◽

Chronic Inflammatory Demyelinating Polyradiculoneuropathy ◽

Protein Inhibitor ◽

Down Regulation ◽

Receiver Operating Characteristic Curves ◽

Immune Mediated ◽

Significant Difference ◽

Gender Based

Protein inhibitors of activated STAT (PIAS) are involved in the regulation of the JAK/STAT signaling pathway and have interactions with NF-κB, p73 and p53. These proteins regulate immune responses; therefore dysregulation in their expression leads to several immune-mediated disorders. In the present study, we examined expression of PIAS1-4 in peripheral blood of patients with acute/chronic inflammatory demyelinating polyradiculoneuropathy (AIDP/CIDP) compared with healthy subjects. We demonstrated down-regulation of all PIAS genes in both AIDP and CIDP cases compared with controls. Similarly, comparisons in gender-based groups revealed down-regulation of these gene0s in patients of each gender compared with gender-matched controls. There was no significant difference in expression of PIAS genes between AIDP and CIDP cases. Based on the area under the receiver operating characteristic curves, PIAS1-4 genes could distinguish between inflammatory demyelinating polyradiculoneuropathy and healthy status with accuracy values of 0.87, 0.87, 0.79 and 0.80, respectively. In differentiation between AIDP cases and healthy controls, these values were 0.92, 0.92, 0.83 and 0.86, respectively. Finally, PIAS1-4 genes could discriminate CIDP from healthy status with accuracy values of 0.82, 0.83, 0.75 and 0.75, respectively. The current study underscores the role of PIAS genes in the pathogenesis of inflammatory demyelinating polyradiculoneuropathy and their potential usage as biomarkers.

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Altered Pharmacokinetics of Piperacillin in Febrile Neutropenic Patients with Hematological Malignancy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02340-14 ◽

2014 ◽

Vol 58 (6) ◽

pp. 3533-3537 ◽

Cited By ~ 25

Author(s):

Fekade Bruck Sime ◽

Michael S. Roberts ◽

Morgyn S. Warner ◽

Uwe Hahn ◽

Thomas A. Robertson ◽

...

Keyword(s):

Standard Deviation ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Hematological Malignancy ◽

Volume Of Distribution ◽

Pharmacokinetic Analysis ◽

Therapeutic Drug ◽

Antibiotic Exposure ◽

Dosing Strategies ◽

Neutropenic Patients

ABSTRACTThis study assessed the pharmacokinetics and dosing adequacy of piperacillin in febrile neutropenic patients after the first dose. Pharmacokinetic analysis was performed using noncompartmental methods. We observed an elevated volume of distribution (29.7 ± 8.0 liters [mean ± standard deviation]) and clearance (20.2 ± 7.5 liters/h) compared to data from other patient populations. Antibiotic exposure did not consistently result in therapeutic targets. We conclude that alternative dosing strategies guided by therapeutic drug monitoring may be required to optimize exposure.

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Glasgow Coma Scale and Its Components on Admission: Are They Valuable Prognostic Tools in Acute Mixed Drug Poisoning?

Critical Care Research and Practice ◽

10.1155/2011/952956 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

N. Eizadi Mood ◽

A. M. Sabzghabaee ◽

Gh. Yadegarfar ◽

A. Yaraghi ◽

M. Ramazani Chaleshtori

Keyword(s):

Glasgow Coma Scale ◽

Operating Characteristic ◽

Attempted Suicide ◽

Mean Value ◽

Study Data ◽

Drug Poisoning ◽

Coma Scale ◽

Receiver Operating Characteristic Curves ◽

Significant Difference ◽

The Mean

Introduction. The verbal, eye, and motor components of Glasgow coma scale (GCS) may be influenced by poisoned patients' behavior in an attempted suicide. So, the values of admission GCS and its components for outcomes prediction in mixed drugs poisoning were investigated.Materials and Methods. A followup study data was performed on patients with mixed drugs poisoning. Outcomes were recorded as without complications and with complications. Discrimination was evaluated by calculating the area under the receiver operating characteristic curves (AUC).Results. There was a significant difference between the mean value of each component of GCS as well as the total GCS between patients with and without complication. Discrimination was best for GCS (AUC:0.933±0.020) and verbal (0.932±0.021), followed by motor (0.911±0.025), then eye (0.89±0.028).Conclusions. Admission GCS and its components seem to be valuable in outcome prediction of patients with mixed drug poisoning.

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Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02466-16 ◽

2017 ◽

Vol 61 (6) ◽

Cited By ~ 10

Author(s):

Catherine J. Byrne ◽

Jason A. Roberts ◽

Brett McWhinney ◽

Jerome P. Fennell ◽

Philomena O'Byrne ◽

...

Keyword(s):

Renal Function ◽

Body Weight ◽

Therapeutic Drug Monitoring ◽

Creatinine Clearance ◽

Trough Concentration ◽

Drug Monitoring ◽

Hematological Malignancy ◽

Therapeutic Drug ◽

Factors Associated ◽

Trough Concentrations

ABSTRACT The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ≥20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P < 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.)

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The significance of strong ion gap for predicting return of spontaneous circulation in patients with cardiopulmonary arrest

Open Medicine ◽

10.1515/med-2017-0006 ◽

2017 ◽

Vol 12 (1) ◽

pp. 33-38

Author(s):

Minoru Kaneko ◽

Shuichi Hagiwara ◽

Makoto Aoki ◽

Masato Murata ◽

Jun Nakajima ◽

...

Keyword(s):

Emergency Department ◽

Operating Characteristic ◽

Cardiopulmonary Arrest ◽

Spontaneous Circulation ◽

Anion Gap ◽

Strong Ion Gap ◽

Return Of Spontaneous Circulation ◽

Receiver Operating Characteristic Curves ◽

Significant Difference ◽

The Difference

AbstractUseful parameters that can predict return of spontaneous circulation (ROSC) in patients with cardiopulmonary arrest (CPA) have not been established. We previously reported the usefulness of anion gap (AG) and albumin-corrected anion gap (ACAG) calculated from a blood sample obtained on arrival at the hospital for the prediction of ROSC. Otherwise, it has been reported that strong ion gap (SIG), which shows the difference between the levels of fully dissociated cations and anions in the serum, is useful to predict the prognosis of critically ill patients.This was a prospective and observational clinical study. Patients with CPA transferred to the emergency department of our hospital between January 2013 and December 2014 were evaluated. Patients were divided into two groups: patients who obtained ROSC [ROSC(+) group] and those who did not [ROSC(−) group]. We compared AG, ACAG and SIG between the two groups.A total of 170 patients were enrolled. Fifty patients were included in the ROSC(+) group, and the remaining 120 in the ROSC(−) group. Both AG and ACAG were significantly better in the ROSC(+) group; however, there was no significant difference in SIG between the two groups. The area under the receiver operating characteristic curves (AUC) for ROSC of both AG and ACAG were almost the same (0.72 and 0.708, respectively); the AUC of SIG (0.57) was inferior to those of AG and ACAG.Our results suggest that AG and ACAG can better predict ROSC following cardiopulmonary resuscitation (CPR) compared with SIG.

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Ten highly sensitive thyrotropin assays compared by receiver-operating characteristic curves analysis: results of a prospective multicenter study.

Clinical Chemistry ◽

10.1093/clinchem/34.4.691 ◽

1988 ◽

Vol 34 (4) ◽

pp. 691-695 ◽

Cited By ~ 9

Author(s):

B Thonnart ◽

O Messian ◽

N C Linhart ◽

B Bok

Keyword(s):

Receiver Operating Characteristic ◽

Multicenter Study ◽

Operating Characteristic ◽

Free Triiodothyronine ◽

Prospective Multicenter Study ◽

Characteristic Curves ◽

Receiver Operating Characteristic Curves ◽

Highly Sensitive ◽

Significant Difference ◽

Receiver Operating

Abstract We report a prospective multicenter study, undertaken to compare the efficacy of 10 highly sensitive thyrotropin assay kits for the diagnosis of hyperthyroidism. Performances of the kits were compared with a reference diagnosis based on clinical examination, pertinent biological tests, and determination by an independent laboratory of the concentrations in serum of free triiodothyronine and free thyroxin. No thyrotropin determination was used in establishing this reference diagnosis. Receiver-operating characteristic curves were obtained for results from 600 patients (217 hyperthyroid and 383 euthyroid) by each kit. Even though analyses were performed out of the working range of most kits, the clinical correlation was nevertheless excellent. The best results corresponded to a sensitivity of 97.5% associated with a specificity of 96.1% and were significantly better than those obtained with all other kits. Results of this comparison depended greatly on the heterogeneity of the "normal"/"abnormal" categories. When only diffuse hyperthyroidism was considered, sensitivity and specificity were improved for all kits, and there was no significant difference among the five best kits.

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Granulocyte Transfusions for Treatment or Prophylaxis of Severe Infections in Immunocompromized Neutropenic Patients - A Randomized Clinical Trial.

Blood ◽

10.1182/blood.v108.11.2934.2934 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2934-2934

Author(s):

Christina Peters ◽

Markus G. Seidel ◽

H. Northoff ◽

R. Moog ◽

A. Boehme ◽

...

Keyword(s):

Fungal Infections ◽

Therapeutic Option ◽

Randomized Study ◽

Underlying Disease ◽

Disease Stage ◽

Hematopoietic Growth Factors ◽

Hematopoietic Stem ◽

Significant Difference ◽

Severe Infections ◽

Neutropenic Patients

Abstract Background: Despite availability of potent anti-bacterial, anti-mycotic drugs and hematopoietic growth factors invasive bacterial or fungal infections remain a severe threat to neutropenic patients after chemotherapy or hematopoietic stem cell transplantation (HSCT). Granulocyte transfusions (GT) from granulocyte colony stimulating factor (G-CSF)-stimulated donors have been shown to increase the leukocyte count prior to expected hematopoietic regeneration, resulting in a shorter period of neutropenia and thus offer a therapeutic option for the control of severe infections. However, published studies rely on clinical observations of individual cases as no statistical comparison with control groups could have been established. The aim of this study was to define the clinical benefit and the leukocyte increment/duration of neutropenia after randomized administration of leukocyte transfusions in immunocompromized neutropenic patients. Patients and methods: Between 1999 and 2005 80 patients with underlying hematological diseases with or without allogeneic or autologous HSCT were randomized to receive either G-CSF, anti-infective treatment according to local standards with or without therapeutic or prophylactic application of GT from G-CSF-stimulated volunteer donors. The mean age was 47 years (range, 14 – 62 y). Indications were either fever in neutropenia and pulmonary infiltrates or soft tissue infiltration (therapeutic) or the history of invasive fungal infection during episodes of neutropenia following earlier chemotherapy courses and anticipated neutropenia of > 10 days (prophylactic). Results: 10 centers participated in the trial, however only five centers recruited patients (n=80) for randomization during the study period. This corresponds to ~50% of the expected sample size of 160 patients, hence results are statistically insignificant. Patient characteristics were comparable within the randomized cohorts (underlying disease, stage of disease, indication for GT, lenght of neutropenia). No significant difference in the clinical outcome was found between patients who received either therapeutic or prophylactic GT from G-CSF stimulated donors or no GT. The probability of survival on day 28 was 85% in both groups. Furthermore, no difference in the incidence and causes of death could be identified within the compared cohorts. Conclusion: The high percentage of infection clearance and survival in patients with severe infections in both groups contrasts with published results and own experiences. We speculate whether this is due a bias in including predominantly patients into the randomized study who presented with relatively favourable prognostic factors, as in the observation period numerous GT were performed in the participating centers without randomization. Most likely, existing clinical evidence for the benefit of this therapeutic measure was sufficient in many cases to exclude patients in serious conditions from randomization. Although well designed, a randomized trial may not always provide the expected results.

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Reducing Gingivitis Remotely using the iGAM mHealth app (part 2): Prospective Observational Study (Preprint)

10.2196/preprints.24955 ◽

2020 ◽

Author(s):

Guy Tobias ◽

Assaf B Spanier

Keyword(s):

Oral Health ◽

Tooth Loss ◽

Prospective Observational Study ◽

Dental Clinics ◽

Significant Difference ◽

Observational Cohort ◽

Group 2 ◽

And Behavior ◽

Oral Hygiene Habits ◽

Group 1

BACKGROUND Gingivitis is a non-painful, inflammatory condition that can be treated with home remedies. Left untreated gingivitis can lead to tooth loss. Periodic dental examinations are important for early diagnosis and treatment of gum diseases. In order to contain the spread of the corona virus, governments, including in Israel, have restricted movements of their citizens which has caused routine dental checkups to be postponed. OBJECTIVE This study aimed to examine the ability of an mHealth app- iGAM to reduce gingivitis. METHODS A prospective observational cohort study was performed, 160 unpaid participants were divided into 2 equal groups and downloaded the iGAM app. Group 1 photographed their gums weekly for eight weeks. Group 2 photographed their gums at the time of recruitment and 8 weeks later. After photo submission, the participants received the message "It is recommended to read the information contained within the app regarding maintaining oral hygiene habits". A single blinded researcher examined the images and scored them according to the Modified Gingival Index (MGI). RESULTS The average age of group 1 was 26.77 (S.D. ± 7.43), and 28.53 (S.D. ± 10.44) for group 2. The majority were male (74.7% in group 1 vs. 66.7% in group 2), most participants described themselves as "secular", most were "single", non-smokers (74.7% vs. 78.4%) and did not take medications (85.3% vs. 78.4%). 126 subjects completed the study. A statistically significant difference (P <.001) was found in the dependent variable (MGI) in a linearly negative manner. As time passed, the gum condition improved, there were significantly lower gingivitis scores in group 1 (M = 1.16, S.D. ± 1.18) compared to group 2 (M = 2.16, S.D. ± 1.49), after eight weeks. Those with more recent dental visits had a lower MGI (p = .037). No association was found between knowledge and behavior, most participants were familiar with the recommendations for maintaining oral health, yet they only performed some. CONCLUSIONS A dental selfie taken once a week using an mHealth app (iGAM) reduced the signs of gingivitis and promoted oral health. During the current pandemic where social distancing recommendations may be causing people to avoid dental clinics, this app can remotely promote gum health. CLINICALTRIAL The protocol was approved by Hadassah research ethics committee (IRB, 0212-18-HMO)

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