bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic drug monitoring of ceftazidime/avibactam: why one leg is not enough to run
Authors: Gatti Milo , Viale Pierluigi , Pea Federico 
Published: November 2023

Abstract

Background
Therapeutic drug monitoring (TDM) is becoming an increasingly recommended approach for assessing optimal pharmacokinetic/pharmacodynamic (PK/PD) target attainment of ceftazidime/avibactam. Some authors hypothesized that the PK/PD target attainment of ceftazidime/avibactam could be assessed by means of the TDM of solely ceftazidime, since avibactam concentrations might be extrapolated based on the fixed 4:1 ceftazidime-to-avibactam ratio present in the vial. The reliability of this hypothesis could be called into question if a wide interindividual variability in the ceftazidime-to-avibactam ratio would exist among patients. This study aimed to assess the distribution of the individual ceftazidime-to-avibactam ratios in relation to renal function in a cohort of adult patients who were treated with continuous infusion ceftazidime/avibactam and underwent TDM of both ceftazidime and avibactam.

Methods
Individual ceftazidime-to-avibactam ratio was calculated at each TDM assessment. Receiving operating characteristics (ROC) curve analysis was performed for testing the potential impact of renal function on ceftazidime-to-avibactam ratio variability.

Results
A total of 188 TDM assessments were collected from 107 patients. The ceftazidime-to-avibactam ratios ranged from 1.29:1 to 13.46:1. Seventy-seven out of 188 ceftazidime-to-avibactam ratios (41.0%) were &gt;5:1, and 36 (19.1%) were &gt;6:1. Patients without renal dysfunction had significantly higher proportions of ceftazidime-to-avibactam ratio &gt;5:1 (59.3% versus 23.8%; P &lt; 0.001) and &gt;6:1 (32.1% versus 6.3%; P &lt; 0.001) compared with those with mild-to-severe renal dysfunction.

Conclusions
The findings may strengthen the contention that for properly assessing the PK/PD target attainment of ceftazidime/avibactam, both ceftazidime and avibactam concentrations should be measured, given the unpredictability of the ceftazidime-to-avibactam ratio occurring among patients.
Biochemical Alterations Associated With the Severity of COVID-19 in Sub-Saharan Black African Individuals
Authors: Moukambi Lydie Armelle , Kande Yatara Marisca , Lendoye Elisabeth , Padzys Guy-Stéphane , Ndeboko Benedict , Maloupazoa Siawaya Anicet Christel , Nzoghe Amandine Mveang , Oliveira Stéphane , Ivala Mendome Yannick , Biyie Bi Ngoghe Prudence , Mvoundza Ndjindji Ofilia , Avome Houechenou Rotimi Myrabelle , Leboueny Marielle , Djoba Siawaya Joel Fleury 
Published: November 2023

Abstract

Background
Biochemical markers are essential in the monitoring and the clinical care of patients as they inform clinicians. Here, we characterized biochemical alterations in sub-Saharan Black African individuals with COVID-19.

Methods
The study includes COVID-19 patients cared for at the Akanda Army Hospital in Libreville (Gabon). A total of 2237 patient records were extracted and reviewed. Patients were classified based on hospital admission (intensive care unit [ICU], internal medicine ward, and outpatient).

Results
One thousand six hundred seventy-one were included in the study. ICU patients were significantly older than non-ICU hospitalized patients (P &lt; 0.001) and outpatients (P &lt; 0.0001). Hyperglycemic patients had 6.4 odds of being in ICU (P &lt; 0.0001). Patients with abnormally high urea had 54.7 odds of being in ICU (P &lt; 0.0001). Patients with abnormally high aspartate aminotransferase (AST) (&gt;33 IU/L) had 3.5 odds of being in ICU (P &lt; 0.0001). Hyperlactatemia (&gt;246 IU/L) odds in ICU patients were 14 (P &lt; 0.0001). The odds of abnormally high alkaline phosphatase (ALP) (&gt;147 IU/L) in ICU patients were 4.6 (P &lt; 0.0001). Odds for hypochloremia (&lt;98 mmol/L) were 1.6 in ICU (P &lt; 0.05). Dysnatremia patients (&lt;135 or &gt;145 mmol/L) had 9.5 odds of being found in ICU patients (P &lt; 0.0001). The odds of potassium imbalance (&lt;3.6 or &gt;5 mmol/L) in ICU patients were 12.2 (P &lt; 0.0001).

Conclusions
COVID-19-associated biochemical alterations observed in the Black African population are similar to those observed in other populations, and the association between COVID-19 severity, hyperglycemia, and multi-organ affection is confirmed.
Prevention of motor ascending branch of the rectus femoris injuries in Bernese periacetabular osteotomy: a cadaveric study
Authors: Lara Joaquín , Garín Alan , Abara Selim , del Río Javier , Besomi Javier , Herrera Cristhián , Cancino Jaime , Villegas Diego , Tobar Carlos 
Published: November 2023

ABSTRACT
The Bernese periacetabular osteotomy (PAO) is a surgical procedure used to treat hip dysplasia in young adults, but it carries the risk of neurological complications, including injury to the motor ascending branch of the rectus femoris (MABRF). This study aimed to describe anatomical considerations to prevent MABRF injuries during PAO. A cadaveric study was conducted on seven specimens. The original and modified PAO approaches were used, with and without disinsertion of the rectus femoris muscle origin. The femoral nerve was dissected in all specimens from the endopelvic position to the MABRF origin (T-point). The average distance from the anterosuperior iliac spine to the T-point was 10.2 ± 0.4 cm. To protect the MABRF, a safety zone was identified for the osteotome placement during the ischial cut. The osteotome was slid over the joint capsule, deflecting the iliocapsularis muscle medially and distally. This manoeuvre shields the MABRF with the iliocapsularis muscle, reducing the risk of neurological injury. Both the original and modified PAO approaches were considered safe techniques with low risk to the rectus femoris innervation. These findings offer valuable insights for surgeons performing PAO, emphasizing the significance of understanding anatomical relationships and implementing protective measures to enhance patient outcomes and minimize complications. In conclusion, implementing these anatomical considerations can help prevent MABRF injuries during PAO, contributing to safer and more successful surgical interventions for hip dysplasia in young adults.
The McMaster osteotomy—a novel surgical treatment to chronic slipped capital femoral epiphysis: description of surgical technique and case study
Authors: Li Zhi , Qiu Reva Y , Khurshed Abdulaziz , Alomran Dana , Williams Dale S , Ayeni Olufemi R , Kishta Waleed 
Published: November 2023

ABSTRACT
Slipped capital femoral epiphysis (SCFE) is a common adolescent hip disorder that can lead to complex proximal femur deformities and devastating consequences such as avascular necrosis, femoroacetabular impingement syndrome and early-onset osteoarthritis. Existing surgical techniques are often insufficient to fully address the constellation of multiplanar deformities in patients with severe SCFE. Therefore, the McMaster Osteotomy, a novel intertrochanteric proximal femur osteotomy, was developed to improve anatomic correction and hip mechanics in patients with chronic SCFE. The McMaster Osteotomy was implemented in two patients (A: 16-year-old male, B: 17-year-old female) with proximal femur deformities due to chronic SCFE. Surgical planning was facilitated with a 3D-printed pelvic model generated from a CT scan of a patient with the SCFE deformity. Patient B also underwent concurrent arthroscopic osteochondroplasty and labral repair. Pre- and post-operative function and radiographic measurements were recorded. Post-operatively, patient A’s neck-shaft angle improved from 125° to 136°, Southwick angle from 52° to 33°, neck length from 66 mm to 80 mm and hip internal rotation from 5° to 25°. Patient B’s post-operative neck-shaft angle improved from 122° to 136°, Southwick angle from 25° to 15°, neck length from 76 mm to 84 mm, hip internal rotation from 5° to 20° and alpha angle from 87.6° to 44.3°. Both patients are pain-free and have obtained full union of their osteotomies. The McMaster Osteotomy is a versatile technique that can produce a more anatomic reconstruction of hip anatomy and restoration of abductor mechanics. As an extracapsular technique, the risk of femoral head avascular necrosis is minimized.
Questionnaire-based scoring system for screening moderate-to-vigorous physical activity in middle-aged Japanese workers
Authors: Adachi Takuji , Ashikawa Hironobu , Funaki Kuya , Kondo Takaaki , Yamada Sumio 
Published: November 2023

Abstract
Objectives: Currently available questionnaires have limited ability to measure physical activity (PA) using accelerometers as a gold standard. This study aimed to develop a PA questionnaire for middle-aged Japanese workers and propose a PA scoring system for predicting low moderate-to-vigorous PA (MVPA).
Methods: A total of 428 participants (median age 49 years; 75.8% men) participated in a 7-day PA measurement using an accelerometer and a questionnaire. The association between questionnaire responses and low MVPA (&lt;150 min/wk) was assessed by logistic regression analysis. A score was assigned to each response based on the correlation coefficients of the multivariate model. The ability of the sum score to predict low MVPA was assessed using the area under the receiver operating characteristic curve (AUC).
Results: Five questionnaire items were used for measuring PA scores (range: 0-50; higher scores indicated a higher probability of low MVPA). The AUC was 0.741 (95% CI, 0.689-0.792), and the sensitivity and specificity at the optimal cut-off value were 66.7% and 68.2%, respectively. This predictive ability was slightly increased by body mass index (AUC 0.745 [95% CI, 0.693-0.796]; sensitivity 69.9%; specificity 66.9%). These predictive values were greater than those of conventional questionnaires used in health checkups in Japan (P &lt; .05).
Conclusions: This questionnaire-based PA scoring system showed moderate accuracy in predicting low MVPA. It is useful for screening physically inactive workers and promoting PA.
Clinical Outcomes of Human Rhinovirus/Enterovirus Infection in Pediatric Hemopoietic Cell Transplant Patients
Authors: Castejon-Ramirez Sandra , Chaisavaneeyakorn Sujittra , Ferrolino Jose A , Allison Kim J , Peterson Megan , Dallas Ronald H , Suliman Ali , Hayden Randall T , Maron Gabriela , Hijano Diego R 
Published: November 2023

Abstract

Background
Respiratory viral infections are common among pediatric transplant patients, with human rhinovirus (HRV) being the most frequent. In pediatric patients undergoing hemopoietic cell transplant (HCT), infection with HRV has been associated with progression to lower respiratory tract infection (LRTI) and adverse outcomes. We describe the clinical presentation and outcomes of HRV infection in children undergoing HCT.

Methods
Single-center retrospective study. HCT recipients who were positive for HRV/EV (HRV+) or negative for any respiratory virus (VN) by BioFire® FilmArray® panel between October 2014 and December 2017, were included. Primary outcomes were progression to LRTI, ICU admission, all-cause mortality at 3 and 6 months, and respiratory event-related mortality at 6 months.

Results
227 patients (160 allogeneic HCT) were included. Of all patients, 108/227 (47.6%) were HRV+. From all HRV+, 95/108 (88%) were symptomatic and 68/107 (63.6%) of the diagnosis were made pretransplant. The median age of HRV+ was significantly lower than VN patients (5 vs 10 years). Cough and rhinorrhea were more frequently observed in HRV+ (53.7 and 60% vs 19.8 and 22.8%, respectively). No differences were found between both groups pretransplant and overall in rates progression to LRTI, ICU admission, mechanical ventilation, all-cause within 3 and 6 months, and mortality related with respiratory failure. No significant association was found between the severity of respiratory disease and the type of conditioning, type of transplant, or absolute lymphocyte count.

Conclusions
HRV infection is frequently detected in HCT recipients but is not associated with severity of respiratory disease, need for intensive care unit or mortality, including those diagnosed before transplant, suggesting that delaying HCT in this scenario may not be needed. Multicenter larger studies are required to confirm these findings.
Music Therapy in Shelters for People Who Are Unhoused: A Scoping Review
Authors: Gregory Dianne , Hernandez Flor , Beach Christopher 
Published: November 2023

Abstract
A scoping review of publications pertaining to music therapy interventions with people who are unhoused and living in shelters was implemented to determine if the available evidence supports professional advocacy and program development with this underserved population at the present time. Searches using EBSCOHost, PsycINFO, ProQuest, and search engines for music therapy journals resulted in 294 publications. Specification of inclusion criteria (population-context-concept) resulted in 13 articles for review to determine the types of evidence, key characteristics of participants and interventions, and gaps and limitations in the literature. An overview of therapists’ descriptions of their sessions’ goals, interventions, and recommendations, combined with information from shelter staff and former participants, provides practical information for interventions and future research. However, the diversity within the small collection of articles prevents generalizations and provides only a glance at possibilities, not a foundation, for professional advocacy and program development.
Journey to kidney transplantation: patient dynamics, suspensions, transplantation and deaths in the Australian kidney transplant waitlist
Authors: De La Mata Nicole L , Khou Victor , Hedley James A , Kelly Patrick J , Morton Rachael L , Wyburn Kate , Webster Angela C 
Published: November 2023

ABSTRACT

Background
People on the kidney waitlist are less informed about potential suspensions. Disparities may exist among those who are suspended and who return to the waitlist. We evaluated the patient journey after entering the waitlist, including suspensions and outcomes, and factors associated with these transitions.

Methods
We included all incident patients waitlisted for their first transplant from deceased donors in Australia from 2006 to 2019. We described all clinical transitions after entering the waitlist. We predicted the restricted mean survival time (unadjusted and adjusted) until first transplant by the number of prior suspensions. We evaluated factors associated with transitions using flexible survival models and clinical endpoints using Cox models.

Results
Of 8466 patients waitlisted and followed over 45 757.4 person-years (median 4.8 years), 6741 (80%) were transplanted, 381 (5%) died waiting and 1344 (16%) were still waiting. A total of 3127 (37%) people were suspended at least once. Predicted mean time from waitlist to transplant was 3.0 years [95% confidence interval (CI) 2.8–3.2] when suspended versus 1.9 years (95% CI 1.8–1.9) when never suspended. Prior suspension increased the likelihood of further suspensions 4.2-fold (95% CI 3.8–4.6) and returning to the waitlist by 50% (95% CI 36–65) but decreased the likelihood of transplantation by 29% (95% CI 62–82). Death risk while waiting was increased 12-fold (95% CI 8.0–18.3) when currently suspended. Australian non-Indigenous males were 13% [hazard ratio (HR) 1.13 (95% CI 1.04–1.23)] and Asian males 23% [HR 1.23 (95% CI 1.06–1.42)] more likely to return to the waitlist compared with females of the same ethnicity.

Conclusion
The waitlist journey was not straightforward. Suspension was common, impacted the chance of transplantation and meant waiting an average of 1 year longer until transplant. We have provided estimates for and factors associated with suspension, relisting and outcomes after waitlisting to support more informed discussions. This evidence is critical to further understand drivers of inequitable access to transplantation.
Inhibition of the glucocorticoid receptor attenuates proteinuric kidney diseases in multiple species
Authors: Stamellou Eleni , Agrawal Shipra , Siegerist Florian , Buse Marc , Kuppe Christoph , Lange Tim , Buhl Eva Miriam , Alam Jessica , Strieder Thiago , Boor Peter , Ostendorf Tammo , Gröne Hermann-Josef , Floege Jürgen , Smoyer William E , Endlich Nicole , Moeller Marcus J 
Published: November 2023

ABSTRACT

Background
Glucocorticoids are the treatment of choice for proteinuric patients with minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS). Immunosuppressive as well as direct effects on podocytes are believed to mediate their actions. In this study, we analyzed the anti-proteinuric effects of inhibition of the glucocorticoid receptor (GR) in glomerular epithelial cells, including podocytes.

Methods
We employed genetic and pharmacological approaches to inhibit the GR. Genetically, we used Pax8-Cre/GRfl/fl mice to specifically inactivate the GR in kidney epithelial cells. Pharmacologically, we utilized a glucocorticoid antagonist called mifepristone.

Results
Genetic inactivation of GR, specifically in kidney epithelial cells, using Pax8-Cre/GRfl/fl mice, ameliorated proteinuria following protein overload. We further tested the effects of pharmacological GR inhibition in three models and species: the puromycin aminonucleoside–induced nephrosis model in rats, the protein overload model in mice and the inducible transgenic NTR/MTZ zebrafish larvae with specific and reversible podocyte injury. In all three models, both pharmacological GR activation and inhibition consistently and significantly ameliorated proteinuria. Additionally, we translated our findings to humans, where three nephrotic adult patients with MCD or primary FSGS with contraindications or insufficient responses to corticosteroids were treated with mifepristone. This treatment resulted in a clinically relevant reduction of proteinuria.

Conclusions
Thus, across multiple species and proteinuria models, both genetic and pharmacological GR inhibition was at least as effective as pronounced GR activation. While the mechanism remains perplexing, GR inhibition may be a novel and targeted therapeutic approach to treat glomerular proteinuria potentially bypassing adverse actions of steroids.
Using a Health Information Exchange to Characterize Changes in HIV Viral Load Suppression and Disparities During the COVID-19 Pandemic in New York City
Authors: Tucker Emma , Reyes Nieva Harry , Schiffer Kayla , Yin Michael T , Castor Delivette , Gordon Peter , Elhadad Noémie , Zucker Jason 
Published: November 2023

Abstract

Background
HIV viral suppression requires sustained engagement in care. The COVID-19 pandemic challenged care accessibility for many people living with HIV (PLWH). We used health information exchange data to evaluate the effect of pandemic-related disruptions in HIV care on viral load suppression (VLS) and to examine racial/ethnic disparities in VLS.

Methods
We performed a retrospective observational cohort study of PLWH using data from a regional health information exchange in the New York City region between 1 January 2018 and 31 December 2022. We established 2 cohorts: PLWH who received HIV care in 2020 (cohort A) and PLWH who did not receive HIV care in 2020 (cohort B). We categorized HIV VLS outcomes as suppressed or not suppressed and calculated the prevalence of VLS between 2018 and 2022. We compared proportions using chi-square tests and used unadjusted and adjusted logistic regression to estimate the association among variables, including race/ethnicity, cohort, and VLS.

Results
Of 5 301 578 patients, 34 611 met our inclusion criteria for PLWH, 11 653 for cohort A, and 3141 for cohort B. In 2019, cohort B had a lower prevalence of VLS than cohort A (86% vs 89%, P &lt; .001). Between 2019 and 2021, VLS dropped significantly among cohort B (86% to 81%, P &lt; .001) while staying constant in cohort A (89% to 89%, P = .62). By 2022, members of cohort B were less likely than cohort A to be receiving HIV care in New York City (74% vs 88%, P &lt; .001). Within both cohorts, Black and Hispanic patients had lower odds of VLS than White patients.

Conclusions
In New York City, VLS remained high among PLWH who continued to receive care in 2020 and dropped among PLWH who did not receive care. VLS was lower among Black and Hispanic patients even after controlling for receipt of care.
5-Flucytosine Longitudinal Antifungal Susceptibility Testing of Cryptococcus neoformans: A Substudy of the EnACT Trial Testing Oral Amphotericin
Authors: McHale Thomas C , Akampurira Andrew , Gerlach Elliot S , Mucunguzi Atukunda , Nicol Melanie R , Williams Darlisha A , Nielsen Kirsten , Bicanic Tihana , Fieberg Ann , Dai Biyue , Meya David B , Boulware David R ,   ENACT Trial Team, Kagimu Enock , Musubire Abdu K , Tugume Lillian , Ssebambulidde Kenneth , Kasibante John , Nsangi Laura , Mugabi Timothy , Gakuru Jane , Kimuda Sarah , Kasozi Derrick , Namombwe Suzan , Turyasingura Isaac , Rutakingirwa Morris K , Mpoza Edward , Kigozi Enos , Muzoora Conrad , Ellis Jayne , Skipper Caleb P , Williams Darlisha A , Hullsiek Kathy H , Abassi Mahsa , Tukundane Asmus , Ndyetukira Jane F , Ahimbisibwe Cynthia , Sadiq Alisat , Kugonza Florence , Nabbale Shifa , Kiiza Tadeo , Namudde Alice , Luggya Tony , Kwizera Richard , Okiror Michael , Babirye Dora , Nanteza Catherine , Mulwana Susan , Muyise Rhona , Kisembo John , Luswata Andrew , Namujju Carol , Laker Eva , Walukaga Stewart , Liu Minda , Engen Nicole , Wele Abduljewad , Rwomushana Irene , Kabahubya Mable , Ssemusu Michael , Mwesigye James , Rukundo Joan , Jjunju Samuel 
Published: November 2023

Abstract

Background
The EnACT trial was a phase 2 randomized clinical trial conducted in Uganda, which evaluated a novel orally delivered lipid nanocrystal (LNC) amphotericin B in combination with flucytosine for the treatment of cryptococcal meningitis. When flucytosine (5FC) is used as monotherapy in cryptococcosis, 5FC can induce resistant Cryptococcus mutants. Oral amphotericin B uses a novel drug delivery mechanism, and we assessed whether resistance to 5FC develops during oral LNC–amphotericin B therapy.

Methods
We enrolled Ugandans with HIV diagnosed with cryptococcal meningitis and who were randomized to receive 5FC and either standard intravenous (IV) amphotericin B or oral LNC–amphotericin B. We used broth microdilution to measure the minimum inhibitory concentration (MIC) of the first and last cryptococcal isolates in each participant. Breakpoints are inferred from 5FC in Candida albicans. We measured cerebral spinal fluid (CSF) 5FC concentrations by liquid chromatography and tandem mass spectrometry.

Results
Cryptococcus 5FC MIC50 was 4 µg/mL, and MIC90 was 8 µg/mL. After 2 weeks of therapy, there was no evidence of 5FC resistance developing, defined as a &gt;4-fold change in susceptibility in any Cryptococcus isolate tested. The median CSF 5FC concentration to MIC ratio (interquartile range) was 3.0 (1.7–5.5) µg/mL. There was no association between 5FC/MIC ratio and early fungicidal activity of the quantitative rate of CSF yeast clearance (R2 = 0.004; P = .63).

Conclusions
There is no evidence of baseline resistance to 5FC or incident resistance during combination therapy with oral or IV amphotericin B in Uganda. Oral amphotericin B can safely be used in combination with 5FC.