bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Evaluation of a Height-Based Tobramycin Initial Dosing Nomogram for the Treatment of Adult Cystic Fibrosis Pulmonary Exacerbations
Authors: El Hassani Mehdi , Thirion Daniel J. G. , Koloskoff Kevin , Matouk Elias , Simard Chantale , Cloutier Isabelle , Pilote Sylvie , Marsot Amélie 
Published: February 2023

Abstract:
Tobramycin is widely used to treat pulmonary exacerbations of cystic fibrosis. Height has been previously found to be significantly more predictive of tobramycin pharmacokinetics than body weight. This study aimed to develop a height-based initial dosing nomogram and evaluate its performance in peak concentration (Cmax) precision relative to standard and fixed dosing. Monte Carlo simulations were performed to develop a nomogram representing the doses required to reach Cmax targets at different heights. Cmax data observed at 2 clinical centers [McGill University Health Centre (MUHC) and Institut universitaire de cardiologie et pneumologie de Québec (IUCPQ-UL)] were compared with population-predicted Cmax using the doses derived from the nomogram alongside a fixed dose. Height-based dosing resulted in significantly less variable-predicted Cmax values [coefficient of variation (CV) MUHC = 15.7% and IUCPQ-UL = 10.8%] than the Cmax values observed in clinical practice (CV MUHC = 30.0% and CV IUCPQ-UL = 26.9%) and predicted Cmax values obtained from a fixed dose (CV MUHC = 21.2% and CV IUCPQ-UL = 16.3%). An initial dosing nomogram was developed to help reduce pharmacokinetic variability in the observed Cmax. More precise dosing would allow for better clinical outcomes in adult patients with cystic fibrosis.
Effect of Therapeutic Plasma Exchange on Itraconazole Pharmacokinetics: A Case Study
Authors: Seah Vincent , Sreeharan Thulashigan , Kocic Danijela , Reuter Stephanie E. , Girgis Laila , Marriott Deborah J. E. , Stocker Sophie L. 
Published: February 2023

Abstract:
The authors present the case of a 34-year-old male patient who underwent therapeutic plasma exchange (TPE) for amyopathic dermatomyositis. Immunosuppression resulted in Aspergillus lentulus pulmonary infection, requiring treatment with super bioavailable-itraconazole. Therapeutic itraconazole concentrations were attained after 2 weeks of treatment after dose adjustments. Interestingly, a substantial reduction in plasma itraconazole concentration was observed during TPE, which was attributed to an insufficient delay between the dosing of itraconazole and TPE initiation. Furthermore, there was an increase in plasma concentration post-TPE, which presumably reflects the redistribution of itraconazole from peripheral compartments back into plasma. This was confirmed by sampling of the TPE plasmapheresate, which revealed that changes in plasma concentration overestimated itraconazole clearance. These findings highlight that the pharmacokinetics of itraconazole are altered during TPE, which should be considered when timing drug administration and obtaining plasma concentrations.
An Unusual Case of Low Vancomycin Exposure Despite Extremely High Vancomycin Doses Accompanied by Renal Toxicity: A Grand Round
Authors: van Schip Anne M. , van Diemen Jeske J. K. , van Hest Reinier M. , Harris Vanessa C. 
Published: February 2023

Abstract:
This grand round describes the case of a patient who received 10 grams (143.5 mg/kg) of vancomycin every 24 hours via continuous infusion, in whom the highest observed level was only 15.4 mg/L. Despite subtherapeutic levels, renal impairment was encountered, which resolved after the discontinuation of vancomycin. Glomerular hyperfiltration was found through nuclear glomerular filtration rate measurement, which likely explains the need for high doses (>6 grams per 24 hours continuous infusion) without reaching therapeutic serum levels.
Diabetes Is Negatively Associated With Meeting Physical Activity Time-Intensity Guidelines in Patients With Claudication
Authors: Gardner Andrew W. , Montgomery Polly S. , Zhang Shangming , Pomilla William A. , Wang Ming , Shen Biyi , Liang Menglu 
Published: February 2023

Purposes:
We determined the percentage of patients with peripheral artery disease (PAD) and claudication who meet the 2018 physical activity (PA) time-intensity guidelines, and we identified the clinical characteristics associated with the status of meeting the guidelines.

Methods:
Five hundred seventy-two patients were assessed on their daily ambulatory activity for 1 wk with a step activity monitor, and were evaluated on whether or not they achieved 150 min/wk of moderate-intensity PA.

Results:
Thirty-one percent (n = 175) of the patients with PAD met the PA time-intensity guidelines and 69% (n = 397) did not. In a final multivariable logistic regression model identifying the independent predictors of meeting the PA time-intensity guidelines from clinical characteristics, diabetes was the only significant variable entered (OR = 0.310: 95% CI, 0.175-0.538; P < .001) and was associated with a 69% lower chance of meeting the guidelines. Patients with diabetes spent less daily time in moderate-intensity ambulatory PA than patients without diabetes (15 ± 13 min/d vs 23 ± 20 min/d; P < .001).

Conclusions:
Thirty-one percent of patients with PAD and claudication met the PA time-intensity guidelines. Furthermore, patients with diabetes were least likely to meet the PA time-intensity guidelines, as they had a 69% lower chance than patients without diabetes. The clinical significance is that PAD patients who have diabetes are particularly susceptible to being physically sedentary, and are therefore prime patients who should be encouraged to increase their daily PA.
The Impact of Underlying Obstructive Sleep Apnea Treatment on Exercise Capacity in Patients With Pulmonary Hypertension Undergoing a Cardiac Rehabilitation Program
Authors: Sykes Alexandra Vaio , Sonners Christine , Schmickl Christopher N. , Raphelson Janna , Swiatkiewicz Iwona , Roberts Erin , Feldman Erica , Malhotra Atul , Taub Pam R. 
Published: February 2023

Purpose:
Obstructive sleep apnea (OSA)–related pulmonary hypertension (PH) can often be reversed with treatment of OSA via continuous positive airway pressure. We hypothesized that treatment of OSA would be associated with a greater improvement in exercise capacity (EC) with cardiac rehabilitation (CR), especially in patients with PH as compared with those who are untreated.

Methods:
We reviewed medical records of 315 consecutive patients who participated in CR. Pulmonary hypertension status was assessed on the basis of peak tricuspid regurgitant velocity (>2.8 m/sec) on pre-CR echocardiograms. The OSA status (no, untreated, or treated OSA) was determined on the basis of results from sleep studies, continuous positive airway pressure device data, and physician notes. Exercise capacity was assessed by measuring metabolic equivalents (METs) using a treadmill stress test before and after CR.

Results:
We included 290 patients who participated in CR with available echocardiographic data: 44 (15%) had PH, and 102 (35%) had known OSA (30 treated and 72 untreated). Patients with OSA versus those with no OSA were more likely to have PH (P = .06). Patients with PH versus no-PH were associated with significantly lower baseline METs in crude and adjusted analyses (P ≤. 004). The PH and OSA status in isolation were not associated with changes in METs (P > .2) with CR. There was a significant interaction between OSA treatment and PH in crude and adjusted analyses (P ≤.01): treatment vs no treatment of OSA was associated with a clinically and statistically greater improvement in METs in patients who participated in CR with but not without PH.

Conclusion:
Baseline PH was associated with decreased baseline EC but did not attenuate CR-related improvements in METs. However, in the subset of OSA patients with PH, OSA therapy was associated with improved EC after CR.
Characteristics and Predictors of Postural Control Impairment in Patients With COPD Participating in a Pulmonary Rehabilitation Program
Authors: Pichon Romain , Ménard Mathieu , Haering Diane , Crétual Armel , Beaumont Marc 
Published: February 2023

Purpose:
Postural control impairment has been identified as a potential extrarespiratory manifestation in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to identify clinical factors that characterize patients with reduced postural control, to examine the correlation between clinical factors and postural control and to determine predictors of an impaired postural control among COPD participants enrolled in a pulmonary rehabilitation (PR) program.

Methods:
This study is a secondary analysis of an observational study (PARACHUTE). The baseline assessment of the PR program was used for the analysis. Postural control impairment was defined using the Brief BESTest score (BBT).

Results:
Participants (n = 73) were included in the analysis, 43 of them were classified in the reduced postural control group. The between-group comparison (non-reduced vs reduced postural control) identified differences for partial pressure in oxygen (PaO
2), Saint George Respiratory Questionnaire (SGRQ) total score and subscores (SGRQ-Symptoms, SGRQ-Activities, and SGRQ-Impact), COPD assessment test (CAT), and anxiety score of the Hospital Anxiety and Depression Scale. The BBT score was significantly correlated with maximal inspiratory pressure (MIP), SGRQ, SGRQ-Symptoms, SGRQ-Impact, Falls Efficacy Scale, modified Medical Research Council Scale, 6-min walk test, and PaO
2. Logistic regression identified SGRQ-Symptoms, PaO
2, MIP, and body mass index (BMI) as predictors of the presence of reduced postural control.

Conclusion:
Low quality of life (QoL) and PaO
2 and high anxiety seem to be discriminative characteristics of patients with COPD with reduced postural control. Furthermore, QoL, PaO
2, inspiratory muscle strength, and BMI seem to be acceptable predictors of the presence of postural control impairment.
Disparities in Adherence to Concussion Clinical Care Recommendations in a Pediatric Population
Authors: Mohammed Fairuz N. , Master Christina L. , Arbogast Kristy B. , McDonald Catherine C. , Sharma Shelly , Kang Boping , Corwin Daniel J. 
Published: February 2023

Objective:
To characterize the relationship of sociodemographic factors to adherence to provider recommendations for pediatric concussion.

Setting:
Primary care (PC) practices within the Children's Hospital of Philadelphia network.

Participants:
Patients aged 5 to 18 years old who presented to any PC site for concussion from September 26, 2019, to December 31, 2019.

Design:
Retrospective medical record review.

Main measures:
The primary outcome was adherence to follow-up recommendations as defined by (1) continued follow-up until provider clearance to return to full activity; (2) no more than 2 no-show visits; and (3) for those referred to specialty care (SC), attending at least 1 visit. We compared adherence by race/ethnicity, insurance, age, sex, injury mechanism, and repeat head injury using bivariate and multivariate analyses. A secondary outcome of referral to SC was compared by sociodemographic factors.

Results:
A total of 755 patients were included. Overall, 80.5% of the patients met adherence criteria. Following adjustment, non-Hispanic Black patients and publicly insured/self-pay patients were less likely to adhere to recommendations than non-Hispanic White patients (adjusted odds ratio [AOR] = 0.60; 95% CI, 0.37-1.00) and privately insured patients (AOR = 0.48; 95% CI, 0.30-0.75), respectively. When assessing differences in referral to SC, non-Hispanic Black patients and publicly insured/self-pay patients were more likely to receive a referral than their non-Hispanic White peers (OR = 1.56; 95% CI, 1.00-2.45) and privately insured patients (OR = 1.56; 95% CI, 1.05-2.32), respectively.

Conclusion:
This study highlights disparities in adherence to concussion care recommendations, with non-Hispanic Black and publicly insured/self-pay patients less likely to adhere to follow-up recommendations than non-Hispanic White and privately insured patients, respectively. These disparities may impact recovery trajectories. Future studies should aim to identify specific individual- and system-level barriers preventing adherence to care in order to ultimately inform targeted interventions to achieve equity in care delivery and outcomes.
Long-Term Risk for Mood and Anxiety Disorders After Pediatric Traumatic Brain Injury: A Population-Based, Birth Cohort Analysis
Authors: Esterov Dmitry , Witkowski Julie , McCall Dana M. , Weaver Amy L. , Brown Allen W. 
Published: February 2023

Objective:
To determine whether exposure to traumatic brain injury (TBI) before 10 years of age is associated with development of a mood or anxiety disorder by 25 years of age, and whether sex or injury severity influences this risk.

Setting:
Olmsted County, Minnesota.

Participants:
A total of 5518 persons born from January 1, 1976, through December 31, 1982.

Design:
Population-based, birth cohort study. Children sustaining TBI before 10 years of age (index date) were confirmed by manual record review and classified by injury severity using the Mayo Classification System. Each TBI case was age- and sex-matched to 2 referents from the same birth cohort without a history of TBI at the index date. Cox proportional hazards models were fit to compare the risk of a subsequent clinically diagnosed mood or anxiety disorder by 25 years of age between TBI cases and referents. Separate analysis was performed stratified by sex and injury severity.

Main Measures:
Incidence of mood and anxiety disorders determined through clinical diagnostic codes and manual record review.

Results:
The study included 562 children (238 females [42.3%] and 324 males [57.7%]) with TBI before 10 years of age (mean [SD] age at TBI: 4.7 [2.8] years). At least 1 mood or anxiety disorder was diagnosed for 115 persons with TBI and 215 referents. No statistically significant association existed between childhood TBI status and anxiety disorder (adjusted hazard ratio [aHR], 1.01 [95% confidence interval (CI), 0.71-1.43]; P = .97) or mood disorder (aHR, 1.16 [95% CI, 0.92-1.47]; P = .21). However, females who sustained TBI had a significantly increased risk of a subsequently diagnosed mood disorder compared with age-matched female referents (aHR, 1.40 [95% CI, 1.04-1.89]; P = .03).

Conclusions:
This study suggests that isolated TBI before 10 years of age is not significantly associated with an increased risk of anxiety or mood disorder by 25 years of age, though females may be at an increased risk.
PREDICTION OF MACULAR HOLE SIZE PROGRESSION BASED ON BASELINE OPTICAL COHERENCE TOMOGRAPHY FINDINGS
Authors: Moussa George , Jalil Assad , Patton Niall , Sabatino Francesco , Jasani Kirti , Dhawahir-Scala Felipe , Sousa David Cordeiro , Ivanova Tsveta 
Published: February 2023

Purpose:
To quantify the rate of idiopathic macular hole progression from presentation and identify factors that may influence stratification and urgency for surgical listing based on the initial optical coherence tomography scans.

Methods:
The minimal linear diameter (MLD), base diameter (BD), and hole height on nasal and temporal sides of idiopathic macular hole were measured on spectral domain optical coherence tomographies, on initial presentation and just before surgery. Mean hole height, hole height asymmetry (absolute difference between nasal and temporal height), MLD/BD, and MLD change per day (MLD/day) were calculated for each patient. Multivariable linear regression analysis with MLD/day as the dependent variable was performed to identify significant risk factors for MLD progression. Minimal linear diameter was grouped to quintiles: 1: ≤290 µm, 2: >290 µm and ≤385 µm, 3: >385 µm and ≤490 µm, 4: >490 µm and ≤623 µm, and 5: >623 µm.

Results:
In 161 eyes (157 patients), we report significant associations with MLD/day: 1) MLD/BD (P = 0.039) (i.e., wide BD relative to MLD lead to faster progression of MLD), 2) hole height asymmetry (P = 0.006) (larger absolute difference between nasal and temporal hole height lead to faster progression), and 3) days between scans (P < 0.001) (longer duration between scans had reduced MLD/day, indicating more rapid increase initially then plateaux), and relative to MLD Quintile 1, MLD Quintile 3 (P = 0.002) and MLD Quintile 4 (P = 0,008), and MLD Quintile 5 (P < 0.001) all lead to a reduced MLD/day rate on multivariable regression.

Conclusion:
In addition to finding that the previously reported initial smaller MLD is a risk factor for rapid MLD progression, we report two novel findings, large hole height asymmetry and a low MLD/BD (wide base relative to MLD), that represent significant risk factors. These factors should be taken into consideration on presentation to stratify timing of surgery.
CORRELATION BETWEEN INFLAMMATORY FOCI REACTIVATION AND ATROPHY GROWTH IN EYES WITH IDIOPATHIC MULTIFOCAL CHOROIDITIS
Authors: Airaldi Matteo , Zicarelli Federico , Forlani Veronica , Casaluci Marco , Oldani Marta , Staurenghi Giovanni , Invernizzi Alessandro 
Published: February 2023

Purpose:
To correlate the number of inflammatory reactivations in atrophic foci of multifocal choroiditis (MFC) with their growth rate over a 4-year span.

Methods:
Comparative case series. Optical coherence tomography scans of patients affected by MFC were reviewed to identify reactivations within or at the margin of atrophic MFC foci. The area of selected lesions was semiautomatically delineated on fundus autofluorescence images and recorded at yearly intervals for a total follow-up of 4 years. The main outcome was the difference in annual square-root transformed area growth rate between lesions that reactivated and lesions that did not.

Results:
Sixty-six foci of 30 eyes of 24 patients were included. All MFC foci enlarged over time, but the annual growth rate was more than double in lesions that reactivated compared with those that did not (mean [SD], 0.051 [0.035] vs. 0.021 [0.015] mm/year, P < 0.001), despite starting from comparable baseline areas. For each additional inflammatory reactivation, the annual growth rate increased by more than 20% (+0.009 mm/year, 95% CI [0.006, 0.012], P < 0.001).

Conclusion:
Increasing number of reactivations of atrophic foci led to proportional increments in their growth rate, highlighting the need for a tight control of inflammatory relapses in patients affected by MFC.
SYRINGE DESIGN AND FILLING TECHNIQUE AFFECT ACCURACY OF ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR INTRAVITREAL INJECTIONS
Authors: Krauthammer Mark , Harel Gal , Moisseiev Elad 
Published: February 2023

Purpose:
To evaluate the effect of syringe design and filling technique on the accuracy of anti–vascular endothelial growth factor delivery.

Methods:
Volume output was measured with three syringe designs: a 1.0-mL slip-tip syringe, a 1.0-mL Luer-lock syringe, and a ranibizumab prefilled syringe—using two filling techniques (“upward” and “downward”) and two fluids (water and bevacizumab). A total of 300 simulated injections were performed. Accuracy was determined by difference from the intended volume of 50 µL and by mean absolute percentage error.

Results:
Volume outputs were significantly different between syringe designs, with mean values of 61.99 ± 4.18 µL with the 1-mL slip-tip syringe, 57.43 ± 4.95 µL with the Luer-lock 1-mL syringe, and 51.06 ± 4.74 µL with the ranibizumab syringe, making the latter the most accurate syringe. There were 37 cases (12.3%) of underdosing below 50 µL, the majority of which occurred with the ranibizumab syringe. The “downward” technique reduced the occurrence of air bubbles.

Conclusion:
Intravitreal injections using 1.0-mL syringes are less accurate than using the ranibizumab prefilled syringe, which has a low-volume and low dead-space plunger design. The variability in volume output may result in less predictable treatment response, especially in cases of underdosing, which were more common with the ranibizumab syringe.
CHARACTERISTICS OF THE MACULAR MICROVASCULATURE IN IDIOPATHIC EPIRETINAL MEMBRANE PATIENTS WITH AN ECTOPIC INNER FOVEAL LAYER
Authors: Yu Hwa-Young , Na Yong-Jin , Lee Sung-Chul , Lee Min-Woo 
Published: February 2023

Purpose:
To identify the characteristics of the retinal microvasculature in epiretinal membrane patients with ectopic inner foveal layer (EIFL).

Methods:
Patients were classified into two groups: those without EIFL (Group 1) and those with EIFL (Group 2). The vessel density (VD), perfusion density (PD), and the foveal avascular zone (FAZ) parameters were compared using optical coherence tomography angiography. Linear regression analysis was performed to identify the optical coherence tomography angiography parameters associated with best-corrected visual acuity.

Results:
The VD of the central area in Group 1 and Group 2 was 11.6 ± 3.3 and 17.2 ± 2.8 mm−1, respectively (P < 0.001), the PD of the central area was 21.7 ± 6.2 and 32.0 ± 5.5%, respectively (P < 0.001), and the FAZ area was 0.24 ± 0.11 and 0.09 ± 0.08 mm2, respectively (P < 0.001). Based on the linear regression analysis, the VD of the central area (B = 0.018, P = 0.003), the PD of the central area (B = 0.009, P = 0.004), and FAZ area (B = −0.489, P = 0.013) were significantly associated with best-corrected visual acuity in patients with epiretinal membrane.

Conclusion:
The VD and PD of the foveal area were significantly higher in patients with EIFL, and the FAZ area was lower in patients with EIFL than in those without EIFL. In addition, the VD and PD of the foveal area were negatively associated with best-corrected visual acuity, and the FAZ area was positively associated with best-corrected visual acuity in patients with epiretinal membrane.
DIRECT MACULAR HOLE MANIPULATION RESULTS IN HIGH SUCCESS RATE IN SECONDARY MACULAR HOLE REPAIR
Authors: Schönbach Etienne M. , Knight Darren K. , Wu Chris Y. , Arevalo J. Fernando , Bittencourt de Souza Luiza , Cheng Lingyun , Chhablani Jay , Delalibera Pacheco Kátia , Feucht Nikolaus , Kozak Igor , Maia André , Maier Mathias , Roizenblatt Marina , Smiddy William E. , Sobol Warren M. , Freeman William R. 
Published: February 2023

Purpose:
To investigate closure rates and functional outcomes of surgery for refractory and recurrent macular holes (MHs) in a real-world setting.

Methods:
Retrospective review of secondary MH surgeries.

Results:
A total of 72 eyes from 72 patients were included. Eyes had a mean of 1.51 surgeries before inclusion into this study with a mean MH size of 762 µm and a mean baseline logarithm of the minimum angle of resolution best-corrected visual acuity of 1.11 (∼20/260 Snellen). Closure rates were 89.3% for tissue transplantation, 77.3% for internal limiting membrane (ILM) flaps, 92.9% for MH manipulation, and 12.5% for repeat ILM peeling (P < 0.05). Best-corrected visual acuity changes in logarithm of the minimum angle of resolution from baseline to postoperative month six were +0.29 for ILM peeling alone (15 Early Treatment Diabetic Retinopathy Study letters worse), −0.39 for MH manipulation (20 Early Treatment Diabetic Retinopathy Study letters improved), −0.23 for tissue transplantation (13 Early Treatment Diabetic Retinopathy Study letters improved), and −0.2 for ILM flaps (10 Early Treatment Diabetic Retinopathy Study letters improved; P < 0.05).

Conclusion:
Secondary MH closure is possible using various surgical techniques with acceptable anatomical closure rates. Repeat ILM peeling is associated with the lowest closure rates and poorest functional results. To distinguish between techniques would require a large sample size of approximately 750 eyes.