bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychometric Properties of the Hindi Version of the Fear-Avoidance Beliefs Questionnaire in Patients With Chronic Non-Specific Low Back Pain
Authors: Panhale Vrushali P. , Gurav Reshma S. , Shah Pooja , Nayak Neelam 
Published: March 2019

Study Design.
Prospective cohort study.

Objective.
To translate, adapt, and establish psychometric properties of the Fear-Avoidance Beliefs Questionnaire (FABQ) for Hindi-speaking patients with chronic non-specific low back pain.

Summary of Background Data.
The FABQ is a patient-reported measure to assess beliefs regarding how physical activity and work are influenced based on fear related to low back pain.

Methods.
Standardized translation guidelines were implemented to confirm Hindi-version of the FABQ (FABQ-H). A cross-sectional study design was utilized. Construct validity analysis included factor analysis of the FABQ and use of Pearson correlation coefficients to report convergent and divergent validity. Reliability assessment included calculation of intraclass correlation coefficient (ICC) and Cronbach α for internal consistency. Outcome measures consisted of Numeric Rating Scale (NRS), Roland Morris Disability Questionnaire (RMDQ) Hindi, and Tampa Scale of Kinesiophobia (TSK).

Results.
In total, 100 patients with chronic non-specific low back pain were recruited, with a mean age of 36.89 (±7.78). Factor analysis revealed a three-factor structure of the FABQ, which consisted of subscales FABQ Physical activity, FABQ Work, and FABQ Work prognosis. Convergent validity analysis demonstrated a moderate correlation between FABQ-H and TSK (r = 0.413). Divergent validity analysis displayed a moderate correlation between FABQ-H and NRS (r = 0.362) and RMDQ Hindi (r = 0.399). ICC value for the FABQ-H was observed as 0.938 indicating high significance for test–retest reliability. Cronbach α for the FABQ-H was recorded as 0.806 demonstrating high internal consistency.

Conclusion.
A successful translation and adaptation of the Hindi version of FABQ is reported in this study. The three-factored FABQ-H exhibited satisfactory construct validity, test–retest reliability, and internal consistency. Based on findings of this study, the FABQ-H can be implemented in Hindi-speaking patients with chronic non-specific low back pain (LBP).

Level of Evidence: 3
The Efficacy of Combining Fractional Carbon Dioxide Laser With Verapamil Hydrochloride or 5-Fluorouracil in the Treatment of Hypertrophic Scars and Keloids: A Clinical and Immunohistochemical Study
Authors: Sabry Hanan H. , Abdel Rahman Sherine H. , Hussein Mohamed S. , Sanad Rana R. , Abd El Azez Taghreed A. 
Published: March 2019

BACKGROUND
Ablative fractional laser-assisted therapy is increasingly used to facilitate drug delivery and intensify clinical efficacy of topically applied drugs.

OBJECTIVE
To evaluate the effectiveness of combined ablative fractional CO2 laser and topically applied 5-fluorouracil (5-FU) or verapamil hydrochloride in the treatment of hypertrophic scars (HTSs) and keloids and to examine their possible effects on TGF-β1 expression.

PATIENTS AND METHODS
Thirty patients with HTSs and keloids were randomly treated with combined CO2 laser followed by topical verapamil or 5-FU application or CO2 laser monotherapy. All patients received 4 treatments at 1-month intervals. Subjective and objective assessment was obtained using the Vancouver Scar Scale (VSS). Histological changes and immunohistochemical staining for TGF-β1 were performed.

RESULTS
Compared with baseline, there was a significant reduction in the VSS 1 month after the last treatment session in all groups (p < .05). Laser-assisted 5-FU delivery tended to show a higher extent of improvement in scar characteristics than laser-assisted verapamil hydrochloride delivery, without significance. No significant side effects were reported in all patient groups. TGF-β1 expression was significantly decreased after laser sessions.

CONCLUSION
Combined fractional CO2 laser and topical 5-FU or verapamil hydrochloride offer a safe therapy for HTSs and keloids.
Nonphysician Practice of Cosmetic Dermatology: A Patient and Physician Perspective of Outcomes and Adverse Events
Authors: Rossi Anthony M. , Wilson Britney , Hibler Brian P. , Drake Lynn A. 
Published: March 2019

BACKGROUND
Nonphysicians are expanding practice into specialty medicine. There are limited studies on patient and physician perspectives as well as safety outcomes regarding the nonphysician practice of cosmetic procedures.

OBJECTIVE
To identify the patient (consumer) and physician perspective on preferences, adverse events, and outcomes following cosmetic dermatology procedures performed by physicians and nonphysicians.

MATERIALS AND METHODS
Internet-based surveys were administered to consumers of cosmetic procedures and physician members of the American Society for Dermatologic Surgery. Descriptive statistics and graphical methods were used to assess responses. Comparisons between groups were based on contingency chi-square analyses and Fisher exact tests.

RESULTS
Two thousand one hundred sixteen commenced the patient survey with 401 having had a cosmetic procedure performed. Fifty adverse events were reported. A higher number of burns and discoloration occurred in the nonphysician–treated group and took place more often in a spa setting. Individuals seeing nonphysicians cited motivating factors such as level of licensure (type) of nonphysician, a referral from a friend, price, and the location of the practitioner. Improper technique by the nonphysician was cited most as a reason for the adverse event. Both groups agree that more regulation should be placed on who can perform cosmetic procedures. Recall bias associated with survey data.

CONCLUSION
Patients treated by nonphysicians experienced more burns and discoloration compared with physicians, and they are encountering these nonphysicians outside a traditional medical office, which are important from a patient safety and regulatory standpoint. Motivating factors for patients seeking cosmetic procedures may also factor into the choice of provider.

KEY POINTS
Both patients and physicians think more regulation should be in place on who can perform cosmetic procedures. More adverse events such as burns and discolorations occurred with patients seeing nonphysicians compared with those seeing physicians. In addition, for those seeing nonphysicians, a majority of these encounters took place in spa settings. Patient safety is of utmost concern when it comes to elective cosmetic medical procedures. More adverse events and encounters occurring outside traditional medical settings when nonphysicians performed these procedures call into question the required training and oversight needed for such procedures.
Pharmacodynamic Monitoring of mTOR Inhibitors
Authors: Millán Olga , Wieland Eberhard , Marquet Pierre , Brunet Mercè 
Published: March 2019

Abstract:
Pharmacodynamic (PD) monitoring may complement routine pharmacokinetic monitoring of mTOR inhibitors (mTORis) in an attempt to better guide individualized sirolimus (SRL) or everolimus (EVR) treatment after organ transplantation. This review focuses on current knowledge about PD biomarkers for personalized mTORi therapies. Different strategies have already been used in the evaluation of the pharmacodynamics of SRL and EVR as a proxy for their effects on the immune response after transplantation. These include measuring p70S6K (70 kDa ribosomal protein S6 kinase) activity, p70S6K phosphorylation (P-p70S6K), or P-S6 protein expression. Compared with Western blot and ELISA, phosphoflow cytometry can detect phosphorylated proteins and differentiate activation-induced changes of signaling molecules inside the cell from unstimulated populations of identical cells in the same sample. Alternatively, in patients receiving a combined therapy, the other PD approach is to consider biomarkers such as NFAT residual expression for calcineurin inhibitors or to evaluate nonspecific effects of the drugs such as lymphocyte proliferation, interleukin synthesis, specific peripheral blood T regulatory subsets, or lymphocyte surface antigens, which have the advantage to reflect the overall immunosuppressive status achieved. Although limited, the available data on mTOR pathway biomarkers seem promising. Before clinical implementation, the analytical methodologies must be standardized and cross-validated, and the selected biomarkers will have to demonstrate their clinical utility for SRL or EVR dose individualization in multicenter clinical trials.
Dolutegravir Population Pharmacokinetics in a Real-Life Cohort of People Living With HIV Infection: A Covariate Analysis
Authors: Parant François , Miailhes Patrick , Brunel Florence , Gagnieu Marie-Claude 
Published: March 2019

Background:
There are growing concerns about dolutegravir (DTG)-related neuropsychiatric adverse events and about differences in the characteristics of people living with HIV infection (PLWH) potentially associated with higher risks of said side effects. Several studies have shown that DTG was stopped more frequently among women, older PLWH, and PLWH who initiated abacavir (ABC) at the same time. This study aimed to clarify the factors affecting the pharmacokinetics (PKs) of DTG in a real-life cohort of PLWH using a population PK approach.

Methods:
The model-building strategy was based on a previously published model developed from premarketing trials (1-compartment model with first-order absorption and a lag time). Sparse therapeutic drug monitoring data were obtained from a real-life cohort of 279 PLWH, and population PK analysis was performed using Monolix software. A stepwise covariate model-building strategy was used to evaluate any relevant effects of age, body weight, gender, total bilirubin, smoking status, formulations of DTG, morning versus evening dosing, backbone therapy, and other comedications including CYP/UGT inducers/inhibitors.

Results:
For a typical 70-kg PLWH, the apparent clearance (CL/F) and apparent volume of distribution (V/F) were 0.748 L/h and 14.6 L, respectively. Of the demographic factors evaluated, body weight was a significant covariate for CL/F and for V/F. Smokers had a 17% higher CL/F relative to nonsmokers. Both strong enzyme inhibitors (eg, atazanavir) and inducers (eg, rifampicin) had marked effects on DTG exposure, with potential clinical implications. Ritonavir-boosted darunavir was found to moderately increase clearance of DTG by 23%. No significant effect of ABC-based backbone therapy was observed on the PK parameters of DTG.

Conclusions:
Our results did not support the hypothesis that ABC, by competing with the DTG metabolic pathway, may significantly increase DTG exposure leading to potential drug toxicity.
Amikacin Pharmacokinetics in Terminal Stage of Hematological Malignancy
Authors: Nakayama Hirokazu , Suzuki Masahiro , Usuki Kensuke , Kato Toshiaki 
Published: March 2019

Background:The influence of cancer cachexia on the pharmacokinetics of and kidney injury caused by amikacin remains unclear. This study investigated whether the pharmacokinetics of amikacin and the risk of kidney injury are altered with the progression of cancer cachexia.Methods:A retrospective analysis was conducted using therapeutic drug monitoring data obtained from 52 cancer patients who received amikacin intravenously for infection(s). The patients were classified into 2 groups based on the status of cachexia using a consensus definition: noncachexia group (n = 31) and cachexia group (n = 21). Differences in amikacin pharmacokinetics and occurrence of kidney injury were compared between the 2 groups. Amikacin pharmacokinetics was calculated based on a 1-compartment model using peak and trough concentrations measured clinically for therapeutic drug monitoring. In addition, intrapatient analysis was conducted based on patients who received amikacin treatments more than once during the study period to examine the alteration in amikacin pharmacokinetics with the progression of cancer cachexia.Results:Systemic clearance of amikacin [median (range)] was significantly (P< 0.05) lower in the cachexia group [37.3 (11.2–87.3) (mL/min)] than in the noncachexia group [52.0 (19.1–133.4) (mL/min)]. In contrast, volume of distribution was significantly (P< 0.05) increased in the cachexia group [0.47 (0.20–1.45) L/kg] compared with the noncachexia group [0.32 (0.21–1.00) L/kg]. There was no difference in the occurrence of kidney injuries between the 2 groups. In an intrapatient analysis of the longitudinal alteration of amikacin pharmacokinetics, an approximately 50% reduction in clearance and 30% increase in volume of distribution were observed as cancer cachexia progressed.Conclusions:The present study suggests that progression of cancer cachexia may reduce amikacin clearance and increase the volume of distribution, but cancer cachexia does not increase amikacin-induced kidney injury.
Examining the Relationship Between Vancomycin Area Under the Concentration Time Curve and Serum Trough Levels in Adults With Presumed or Documented Staphylococcal Infections
Authors: Clark Laura , Skrupky Lee P. , Servais Ryan , Brummitt Charles F. , Dilworth Thomas J. 
Published: March 2019

Background:
Investigations of the relationship between vancomycin trough concentrations and area under the concentration time curve (AUC) are growing, but still limited. The authors sought to determine vancomycin exposure among hospitalized adults with presumed or confirmed invasive staphylococcal infections using 2-level pharmacokinetic monitoring to inform changes to an institutional vancomycin dosing protocol.

Methods:
This was a retrospective observational study performed in 2 acute care hospitals. Adults prescribed vancomycin (therapeutic trough 15–20 mg/L) for a presumed or documented invasive staphylococcal infection were evaluated. Two steady-state serum vancomycin levels were used to determine each patient's 24-hour AUC to minimum inhibitory concentration ratio (AUC/MIC) using a non-Bayesian, equation-based approach. Patient demographics and crude clinical outcomes were also collected.

Results:
Thirty-four patients were included in the study, with 2 patients having vancomycin levels drawn twice (36 sets of levels). Most patients were located in an intensive care unit (91.2%), and 85.3% of patients were prescribed vancomycin for bacteremia, pneumonia, or endocarditis. The mean ± SD vancomycin Cmin was 16.6 ± 6.1 mg/L, and the mean AUC/MIC was 588 ± 156 mg/L × hour. The rate of 24-hour vancomycin AUC/MIC target attainment was 91.2% (n = 31/34). Of the patients with a Cmin > 9 mg/L, 100% (n = 33) achieved AUC/MIC values >400 mg/L × hour and 93.9% were >500 mg/L × hour. There was a strong correlation between vancomycin Cmin and AUC24 hr (R2 = 0.731; P < 0.001).

Conclusions:
Targeting a vancomycin trough between 15 and 20 mg/L frequently resulted in an AUC/MIC greater than that thought to be necessary for efficacy optimization. Considering these findings alongside the practical challenges associated with wide-scale implementation of AUC monitoring, reducing the target trough as a means to prevent vancomycin overexposure warrants clinical consideration and further evaluation.
Pharmacodynamic Monitoring of Antiepileptic Drug Therapy
Authors: Brandt Christian 
Published: March 2019

Abstract:
Epilepsy is characterized by seizures recurring at interindividually differing time intervals. It may be difficult to assess drug response if time intervals between seizures are long. Thus, the existence of surrogate parameters that could be used to reliably identify drug efficacy and tolerability at an early stage and also as prognostic factors would be desirable. Electroencephalography, magnetic resonance imaging, and genetic markers are the domains to be assessed in this respect. The availability of clinically useful pharmacodynamic parameters is, however, currently disappointing.
Strategies for Individualized Dosing of Clotting Factor Concentrates and Desmopressin in Hemophilia A and B
Authors: Preijers Tim , Schütte Lisette M. , Kruip Marieke J. H. A. , Cnossen Marjon H. , Leebeek Frank W. G. , van Hest Reinier M. , Mathôt Ron A. A. 
Published: March 2019

Abstract:Hemophilia A and hemophilia B are hereditary bleeding disorders, caused by a deficiency of clotting factor VIII or clotting factor IX, respectively. To treat and prevent bleedings, patients can administer clotting factor concentrates (hemophilia A and B) or desmopressin (hemophilia A). Both clotting factor concentrates and desmopressin are currently dosed according to the patients' body weight. However, clotting factor concentrates exhibit considerable pharmacokinetic (PK) variability. Therefore, several alternative dosing strategies to individualize dosing of clotting factor concentrates and desmopressin in hemophilia A and B have been proposed. In this study, a review of the existing literature on the individualization of dosing based on PK guidance was performed. In total, 79 articles were included. The methods to individualize dosing were divided into 3 categories: (1) methods using clinical parameters, (2) empirical individual PK-guided methods, and (3) maximum a posteriori (MAP) Bayesian estimation methods. The clinical parameter mainly used to individualize dosing is bleeding phenotype. Dosing based on bleeding phenotype may decrease clotting factor consumption. However, with this method, it is not possible to individualize on-demand dosing during bleeding events or in the perioperative setting. Empirical individual PK-guided methods can be used both for prevention and treatment of bleedings. These methods include dose individualization using a nomogram and individualized in vivo recovery. In the perioperative setting, adjustment of the rate of continuous infusion can be applied to obtain a specific target level. The final category, MAP Bayesian estimation methods, relies on the availability of a population PK model. In total, 22 population PK models describing clotting factor concentrate or desmopressin dosing are currently available in literature. MAP Bayesian estimates can be used to calculate the individualized doses required to achieve or maintain a target level in every setting. The application of PK-guided and pharmacodynamic-guided dosing of clotting factor concentrates and desmopressin seems promising, although further investigation is warranted. Prospective studies analyzing its potential benefit are on the way.
Tolerability of Erythrocyte Ribavirin Triphosphate Concentrations Depends on the ITPA Genotype
Authors: Tanaka Yoichi , Inoue Akiko , Mizunuma Tomohiko , Matsumura Haruka , Yokomori Hiroaki , Komiyama Takako , Otori Katsuya 
Published: March 2019

Background:
Ribavirin (RBV) is an antiviral drug that is part of the current standard therapy for chronic hepatitis C (CHC). It is enzymatically converted to ribavirin triphosphate (RTP) that inhibits the activity of viral RNA polymerase, thereby preventing viral replication. However, one of its adverse effects includes hemolytic anemia that limits its application. The variant of ITPA (inosine triphosphatase), which dephosphorylates inosine triphosphate to inosine monophosphate, is a protective factor for RBV-induced anemia. RTP is an important metabolite required for ribavirin action. This study evaluated the time-dependent association of RTP concentrations in erythrocytes, RBV-induced toxicity, and virological response to RBV treatment for hepatitis C.

Methods:
A total of 28 Japanese patients with CHC were treated with RBV/peg-interferon/simeprevir or RBV/sofosbuvir and were genotyped for ITPA variants (rs1127354 and rs7270101). We measured RTP concentrations in erythrocytes in a total of 76 samples collected at 4, 8, and 12 weeks from the initiation of treatment.

Results:
The ITPA rs1127354 variant was found in 7 patients. This was associated with significantly higher RTP concentrations in erythrocytes than in the wild-type patients (P < 0.001). Moreover, a significant correlation was observed between RTP concentrations and decline in hemoglobin (Hb) levels from baseline values in ITPA wild type and rs1127354 variant 12 weeks after treatment initiation (P < 0.01; r = −0.618 and −0.967, respectively). Multiple regression analysis revealed that ITPA genotype and erythrocyte RTP concentrations were major factors associated with reduced Hb levels in RBV therapy for CHC. However, we did not find any association between erythrocyte concentrations and virological response.

Conclusions:
The increased tolerability to RTP concentrations in erythrocytes in the ITPA variant rs1127354 plays a role in preventing RBV-induced severe anemia in this ITPA variant.
Comparison of Immunoassays for Measuring Serum Levels of Golimumab and Antibodies Against Golimumab in Ulcerative Colitis: A Retrospective Observational Study
Authors: Berger Anne-Emmanuelle , Duru Gerard , de Vries Annick , Marini Joseph C. , Aoucheta Djamila , Cornillie Freddy , Nancey Stephane , Detrez Iris , Gils Ann , Roblin Xavier , Paul Stephane 
Published: March 2019

Background:
Golimumab is a monoclonal anti–tumor necrosis factor alpha antibody, which is used in ulcerative colitis with an exposure–response relationship. The goal of this study was to compare results obtained with different immunoassays (golimumab and antigolimumab antibodies trough levels).

Methods:
This study was based on samples from 78 ulcerative colitis patients on golimumab treatment. Golimumab was quantified by either an anti-IgG detection antibody (Theradiag, Marne la Vallée, France) or an antibody directed against golimumab (Sanquin, Amsterdam, The Netherlands, KU Leuven, Leuven, Belgium, and Janssen R&D, San Diego, CA). Bridging drug-sensitive enzyme-linked immunosorbent assays (Theradiag, Janssen R&D, and KU Leuven), a bridging drug-tolerant enzyme-linked immunosorbent assay (Janssen R&D), and a radioimmunoassay (Sanquin) were used to quantify antidrug antibody.

Results:
Median serum golimumab levels were 4.5, 3.5, 4.9, and 2.4 mcg/mL with Theradiag, Sanquin, KU Leuven, and Janssen R&D assay, respectively (P < 0.05). Correlation coefficients between assays ranged from 0.9 to 0.97. When using the KU Leuven and Janssen R&D assays, 86% of samples were in the same quartile of distribution of values, and for Sanquin and Janssen R&D assays, this overlap was 80%. The concordance observed for the other pairs was 83% (Sanquin/KU Leuven R&D), 71% (Theradiag/KU Leuven), and 68% (Theradiag/Janssen R&D and Theradiag/Sanquin). The specificity of assays for golimumab was demonstrated. Antidrug antibodies were detected in 28.2% of the samples with the Janssen R&D drug-tolerant assay and in the same 2 patients by the 3 other assays.

Conclusions:
Performances of these immunoassays were similar in terms of quality, but differences in the quantitative results point to the importance of using the same assay consistently to monitor a patient's treatment.