bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Critical Review of Genetic Factors Associated with Cisplatin-induced Ototoxicity: Canadian Pharmacogenomics Network for Drug Safety 2022 Update
Authors: Scott Erika N. , Joseph Akshaya A. , Dhanda Angie , Tanoshima Reo , Brooks Beth , Rassekh S. Rod , Ross Colin J.D. , Carleton Bruce C. , Loucks Catrina M. 
Published: September 2023

Background:
Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic variants has been associated with the development/occurrence of cisplatin-induced ototoxicity, suggesting that genetic factors may be able to predict patients who are more likely to develop ototoxicity. The authors aimed to review genetic associations with cisplatin-induced ototoxicity and discuss their clinical relevance.

Methods:
An updated systematic review was conducted on behalf of the Canadian Pharmacogenomics Network for Drug Safety, based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement. Pharmacogenomic studies that reported associations between genetic variation and cisplatin-induced ototoxicity were included. The evidence on genetic associations was summarized and evaluated, and knowledge gaps that can be used to inform future pharmacogenomic studies identified.

Results:
Overall, 40 evaluated reports, considering 47 independent patient populations, captured associations involving 24 genes. Considering GRADE criteria, genetic variants in 2 genes were strongly (ie, odds ratios ≥3) and consistently (ie, replication in ≥3 independent populations) predictive of cisplatin-induced ototoxicity. Specifically, an ACYP2 variant has been associated with ototoxicity in both children and adults, whereas TPMT variants are relevant in children. Encouraging evidence for associations involving several other genes also exists; however, further research is necessary to determine potential clinical relevance.

Conclusions:
Genetic variation in ACYP2 and TPMT may be helpful in predicting patients at the highest risk of developing cisplatin-induced ototoxicity. Further research (including replication studies considering diverse pediatric and adult patient populations) is required to determine whether genetic variation in additional genes may help further identify patients most at risk.
Axial Length Control Is Associated With a Choroidal Thickness Increase in Myopic Adolescents After Orthokeratology
Authors: Wang Zhiqian , Chen Jingyi , Kang Jingxiong , Niu Tongtong , Guo Lei , Fan Liying 
Published: September 2023

Objective:
To investigate the changes in choroidal thickness and axial length after orthokeratology in adolescents with low-to-moderate myopia and to explore the relationship between choroidal thickness and axial length variation.

Methods:
Thirty eyes with low-to-moderate myopia were retrospectively studied, and optometric data were collected before and after 6 months of continuous orthokeratology. Axial length and choroidal and foveal thicknesses were measured using optical biometry and enhanced depth imaging–spectral domain optical coherence tomography, respectively.

Results:
Axial length in the low myopia group increased (P<0.001) after 6 months of orthokeratology, and the variation was greater than that in the moderate myopia group (P<0.05). The subfoveal choroidal thickness in low and moderate myopia groups increased (P<0.01), and the variation was greater in the moderate myopia group (P<0.05). Choroidal thickness in all seven measured spots increased, with the variation of subfovea, nasal 1 mm to fovea, and temporal 1 mm to fovea being statistically significant (P<0.001, P<0.05, and P<0.05). The change in axial length was negatively associated with subfoveal and average choroidal thicknesses (P<0.01).

Conclusion:
Adolescents with moderate myopia presented better axial length control after 6 months of orthokeratology. The choroidal thickness of low and moderate myopic eyes increased, and the variation was more significant in moderate myopic eyes. The axial length control effects can be associated with an increase in the subfoveal and average choroidal thickness.
Comparison between linear regression and four different machine learning methods in selecting risk factors for osteoporosis in a Chinese female aged cohort
Authors: Tzou Shiow-Jyu , Peng Chung-Hsin , Huang Li-Ying , Chen Fang-Yu , Kuo Chun-Heng , Wu Chung-Ze , Chu Ta-Wei 
Published: September 2023

Background:
Population aging is emerging as an increasingly acute challenge for countries around the world. One particular manifestation of this phenomenon is the impact of osteoporosis on individuals and national health systems. Previous studies of risk factors for osteoporosis were conducted using traditional statistical methods, but more recent efforts have turned to machine learning approaches. Most such efforts, however, treat the target variable (bone mineral density [BMD] or fracture rate) as a categorical one, which provides no quantitative information. The present study uses five different machine learning methods to analyze the risk factors for T-score of BMD, seeking to (1) compare the prediction accuracy between different machine learning methods and traditional multiple linear regression (MLR) and (2) rank the importance of 25 different risk factors.

Methods:
The study sample includes 24 412 women older than 55 years with 25 related variables, applying traditional MLR and five different machine learning methods: classification and regression tree, Naïve Bayes, random forest, stochastic gradient boosting, and eXtreme gradient boosting. The metrics used for model performance comparisons are the symmetric mean absolute percentage error, relative absolute error, root relative squared error, and root mean squared error.

Results:
Machine learning approaches outperformed MLR for all four prediction errors. The average importance ranking of each factor generated by the machine learning methods indicates that age is the most important factor determining T-score, followed by estimated glomerular filtration rate (eGFR), body mass index (BMI), uric acid (UA), and education level.

Conclusion:
In a group of women older than 55 years, we demonstrated that machine learning methods provide superior performance in estimating T-Score, with age being the most important impact factor, followed by eGFR, BMI, UA, and education level.
Incidence of Vulvar Lichen Sclerosus and of Cancer Among Vulvar Lichen Sclerosus Patients: Does Socioeconomic Status Have a Role?
Authors: Borghi Alessandro , Ferretti Stefano , Pacetti Lucrezia , Falcini Fabio , Corazza Monica 
Published: September 2023

Objective
Socioeconomic status (SES) impacts on the incidence of many inflammatory diseases and cancers, but there is no evidence on its implication in vulvar lichen sclerosus (VLS). The authors aimed to assess possible associations between SES and both occurrence of VLS and cancer occurrence among VLS patients.

Materials and Methods
A retrospective cohort of women resident in the province of Ferrara, Italy, affected with VLS diagnosed between 2001 and 2020, was investigated for assessing any association of SES with VLS and cancer incidence. The SES was expressed through an ecological-based deprivation index identifying 5 subgroups.

Result
Four-hundred women were diagnosed with VLS during the study period, with double the number of cases in the second decade (2011–2020) compared with the first (2001–2010). More VLS patients belonged to the high rather than the low SES groups (p = .032). From VLS diagnosis to 2018 (1,958.4 total person*years at risk), 22 patients received their first diagnosis of cancer, mainly the skin, breast, and vulva. No significant differences in cancer incidence were found between high/medium-high and low/medium-low SES subjects.

Conclusions
The fact that more VLS patients belonged to the highest socioeconomic classes may be due to a more frequent diagnosis in those with greater health seeking behavior and resources. An involvement of SES-related factors in VLS pathophysiological background can also be taken into consideration. Both the lack of marked social and economic differences in the study area and the availability of free visits and screening may account for the lack of association between SES and cancer development.
Role of protein induced by vitamin-K absence-II in transplanted patients with HCC not producing alpha-fetoprotein
Authors: Lai Quirino , Ito Takashi , Iesari Samuele , Ikegami Toru , Nicolini Daniele , Larghi Laureiro Zoe , Rossi Massimo , Vivarelli Marco , Yoshizumi Tomoharu , Hatano Etsurou , Lerut Jan 
Published: September 2023

Elevated Protein Induced by Vitamin-K Absence-II (PIVKA-II) has been shown to be an adverse prognostic factor in HCC patients undergoing liver transplantation (LT). No definitive data are available about the impact of PIVKA-II concerning post-LT recurrence in patients not secreting (≤ 20 ng/mL) alpha-fetoprotein (AFP). An observational retrospective study of the East-West HCC-LT consortium is reported. Between 2000 and 2019, 639 HCC patients were enrolled in 5 collaborative European and Japanese centers. To minimize the initial selection bias, an inverse probability therapy weighting method was adopted to analyze the data. In the post-inverse probability therapy weighting population, PIVKA-II (HR = 2.00; 95% CI: 1.52–2.64; p < 0.001) and AFP (HR=1.82; 95% CI: 1.48–2.24; p < 0.001) were the most relevant independent risk factors for post-LT recurrence. A sub-analysis focusing only on patients who are AFP non-secreting confirmed the negative role of PIVKA-II (HR=2.06, 95% CI: 1.26–3.35; p=0.004). When categorizing the entire population into 4 groups according to the AFP levels (≤ or > 20 ng/mL) and PIVKA (≤ or > 300 mUA/mL) at the time of LT, the lowest recurrence rates were observed in the low AFP-PIVKA-II group (5-year recurrence rate = 8.0%). Conversely, the high AFP-PIVKA-II group had the worst outcome (5-year recurrence rate = 35.1%). PIVKA-II secretion is a relevant risk factor for post-LT HCC recurrence. The role of this marker is independent of the AFP status. Combining both tumor markers, especially in the setting of LT, should be of great relevance for adding information about predicting the post-LT risk of tumor recurrence and selecting these patients for transplantation.
Feasibility of a selective targeted strategy of HIV testing in emergency departments: a before-after study
Authors: González del Castillo Juan , Mirò Emília , Miguens Iria , Trenc Patricia , Espinosa Begoña , Piedrafita Lourdes , Pérez Elías María Jesús , Moreno Santiago , García Federico , Villamor Alberto , Carbó Míriam , Gené Emili , Mirò Òscar ,   on behalf of the Emergency HIV network investigators
Published: September 2023

Background and importance
The rates of hidden infection and late diagnosis of HIV still remain high in Western countries. Missed diagnostic opportunities represent the key point in changing the course of the epidemic.

Objective
To evaluate the feasibility and results of implementation of a selective strategy to test for HIV in the emergency department (ED) in patients with six pre-defined medical situations: sexually transmitted infections, herpes zoster, community-acquired pneumonia, mononucleosis syndrome, practice of chemsex (CS) or request of post-exposure prophylaxis.

Design
This quasi-experimental longitudinal study evaluated the pre- and post-implementation results of HIV testing in the six aforementioned clinical scenarios.

Settings and participants
Patients attended 34 Spanish EDs.

Intervention or exposure
The intervention was an intensive educational program and pathways to facilitate and track orders and results were designed. We collected and compared pre- and post-implementation ED census and diagnoses, and HIV tests requested and results.

Outcome measures and analysis
The main outcome was adherence to the recommendations. Secondary outcomes were to evaluate the effectiveness of the program by the rate of positive test and the new HIV diagnoses. Differences between first and second periods were assessed. The magnitude of changes (absolute and relative) was expressed with the 95% confidence interval (CI).

Main results
HIV tests increasing from 7080 (0.42% of ED visits) to 13 436 (relative increase of 75%, 95% CI from 70 to 80%). The six conditions were diagnosed in 15 879 and 16 618 patients, and HIV testing was ordered in 3393 (21%) and 7002 (42%) patients (increase: 97%; 95% CI: 90–104%). HIV testing significantly increased for all conditions except for CS. The positive HIV test rates increased from 0.92 to 1.67%. Detection of persons with undiagnosed HIV increased from 65 to 224, which implied a 220% (95% CI: 143–322%) increase of HIV diagnosis among all ED comers and a 71% (95% CI: 30–125%) increase of positive HIV tests.

Conclusion
Implementation of a strategy to test for HIV in selective clinical situations in the ED is feasible and may lead to a substantial increase in HIV testing and diagnoses.
Gastrointestinal Biomarkers and Their Association with Feeding in the First Five Days of Pediatric Critical Illness
Authors: Veldscholte Karlien , Hulst Jessie M. , Eveleens Renate D. , de Jonge Rogier C.J. , de Koning Barbara A.E. , van den Berg Sjoerd A.A. , van der Wal Ronald , Ruijter George J.G. , Rizopoulos Dimitris , Vanhorebeek Ilse , Gunst Jan , Casaer Michaël , Van den Berghe Greet , Joosten Koen F.M. , Verbruggen Sascha C.A.T. 
Published: September 2023

Objectives:
Predicting the patients’ tolerance to enteral nutrition (EN) would help clinicians optimize individual nutritional intake. This study investigated the course of several gastrointestinal (GI) biomarkers and their association with EN advancement (ENA) longitudinally during pediatric intensive care unit (PICU) admission.

Methods:
This is a secondary analysis of the Early versus Late Parenteral Nutrition in the Pediatric Intensive Care Unit randomized controlled trial. EN was started early and increased gradually. The cholecystokinin (CCK), leptin, glucagon, intestinal fatty acid-binding protein 2 (I-FABP2), and citrulline plasma concentrations were measured upon PICU admission, day 3 and day 5. ENA was defined as kcal EN provided as % of predicted resting energy expenditure. The course of the biomarkers and ENA was examined in patients with samples on all time points using Friedman and Wilcoxon signed-rank tests. The association of ENA with the biomarkers was examined using a 2-part mixed-effects model with data of the complete population, adjusted for possible confounders.

Results:
For 172 patients, median age 8.6 years (first quartile; third quartile: 4.2; 13.4), samples were available, of which 55 had samples on all time points. The median ENA was 0 (0; 0) on admission, 14.5 (0.0; 43.8) on day 3, and 28.0 (7.6; 94.8) on day 5. During PICU stay, CCK and I-FABP2 concentrations decreased significantly, whereas glucagon concentrations increased significantly, and leptin and citrulline remained stable. None of the biomarkers was longitudinally associated with ENA.

Conclusions:
Based on the current evidence, CCK, leptin, glucagon, I-FABP2, and citrulline appear to have no added value in predicting ENA in the first 5 days of pediatric critical illness.
A Forensic Case of Suicide Ingestion of Paraquat Herbicide
Authors: Tambuzzi Stefano , Vacchiano Laura , Gentile Guendalina , Boracchi Michele , Zoja Riccardo , Migliorini Arnaldo Stanislao 
Published: September 2023

Abstract
Paraquat (PQ) is one of the most widely used herbicides in the world, and poisoning is generally associated with accidental, suicidal, or homicidal events. Therefore, in the forensic context, PQ could be in various ways involved as a possible cause of death of a subject. However, even though its systemic toxicity is known, the biological effects exerted on individual viscera have been explored only to some extent, especially in case of victim's survival. Therefore, a case concerning a suicidal ingestion of PQ with survival of 3 days was deemed of interest. Clinical toxicological analyses confirmed acute PQ intoxication, and after the death of the victim, an autopsy was performed showing local and systemic signs of ingestion of a caustic substance. Histologic examination revealed marked cellular damage to the major viscera, particularly the gastroesophageal tract, liver, kidneys, and lungs, with initial alveolar fibrosis noted despite the patient's short survival. This finding represents a new element in the context of PQ lung injury, as it has not been previously documented in the literature. Thus, histological findings in lethal intoxications after survival can reveal specific peculiarities still unknown and, therefore, assume transversal relevance not only at forensic but also clinical level.
Reduced Postdischarge Incidents After Implementation of a Hospital-to-Home Transition Intervention for Children With Medical Complexity
Authors: Huth Kathleen , Hotz Arda , Emara Norah , Robertson Bryanna , Leaversuch Marissa , Mercer Alexandra N. , Khan Alisa , Campos Maria-Lucia , Liss Isabella , Hahn Phillip D. , Graham Dionne A. , Rossi Laura , Thomas Margaret V. , Elias Nahel , Morris Marie , Glader Laurie , Pinkham Amy , Bardsley Kristin M. , Wells Sarah , Rogers Jayne , Berry Jay G. , Mauskar Sangeeta , Starmer Amy J. 
Published: September 2023

Objectives
Prior research suggests that errors occur frequently for patients with medical complexity during the hospital-to-home transition. Less is known about effective postdischarge communication strategies for this population. We aimed to assess rates of 30-day (1) postdischarge incidents and (2) readmissions and emergency department (ED) visits before and after implementing a hospital-to-home intervention.

Methods
We conducted a prospective intervention study of children with medical complexity discharged at a children’s hospital from April 2018 to March 2020. A multistakeholder team developed a bundled intervention incorporating the I-PASS handoff framework including a postdischarge telephone call, restructured discharge summary, and handoff communication to outpatient providers. The primary outcome measure was rate of postdischarge incidents collected via electronic medical record review and family surveys. Secondary outcomes were 30-day readmissions and ED visits.

Results
There were 199 total incidents and the most common were medication related (60%), equipment issues (15%), and delays in scheduling/provision of services (11%). The I-PASS intervention was associated with a 36.4% decrease in the rate of incidents per discharge (1.51 versus 0.95, P = 0.003). There were fewer nonharmful errors and quality issues after intervention (1.27 versus 0.85 per discharge, P = 0.02). The 30-day ED visit rate was significantly lower after intervention (12.6% versus 3.4%, per 100 discharges, P = 0.05). Thirty-day readmissions were 15.8% versus 10.2% postintervention (P = 0.32).

Conclusions
A postdischarge communication intervention for patients with medical complexity was associated with fewer postdischarge incidents and reduced 30-day ED visits. Standardized postdischarge communication may play an important role in improving quality and safety in the transition from hospital-to-home for vulnerable populations.
Associations Between Hospitalist Shift Busyness, Diagnostic Confidence, and Resource Utilization: A Pilot Study
Authors: Gupta Ashwin B. , Greene M. Todd , Fowler Karen E. , Chopra Vineet I. 
Published: September 2023

Objectives
Hospitalized patients are at risk for diagnostic errors. Hospitalists caring for these patients are often multitasking when overseeing patient care. We aimed to measure hospitalist workload and understand its influences on diagnostic performance in a real-world clinical setting.

Methods
We conducted a single-center, prospective, pilot observational study of hospitalists admitting new patients to the hospital. Hospitalists completed an abridged Mindful Attention Awareness Tool and a survey about diagnostic confidence at shift completion. Data on differential diagnoses and resource utilization (e.g., laboratory, imaging tests ordered, and consultations) were collected from the medical record. The number of admissions and paging volume per shift were used as separate proxies for shift busyness. Data were analyzed using linear mixed effects models (continuous outcomes) or mixed effects logistic regression (dichotomous outcomes).

Results
Of the 53 hospitalists approached, 47 (89%) agreed to participate; complete data were available for 37 unique hospitalists who admitted 160 unique patients. Increases in admissions (odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82; P = 0.04) and pages (odds ratio, 1.11; 95% CI, 1.02 to 1.21; P = 0.01) were associated with increased odds of hospitalists finding it “difficult to focus on what is happening in the present.” Increased pages was associated with a decrease in the number of listed differential diagnoses (coefficient, −0.02; 95% CI, −0.04 to −0.003; P = 0.02).

Conclusions
Evaluation of hospitalist busyness and its associations with factors that may influence diagnosis in a real-world environment was feasible and demonstrated important implications on physician focus and differential diagnosis.
Adverse Event Reporting of Commonly Used Gender-Specific Implantable Medical Devices in the United States
Authors: Pierce Hudson , Ahsan Muhammad Danyal , Martinez Diaz Susana , Cho Ahra , Asfaw Tirsit , Mao Jialin , Anger Jennifer , Chughtai Bilal 
Published: September 2023

Background
Evidence suggests that more women are harmed by implantable medical devices than men. It is unknown whether this difference includes gender-specific devices.

Methods
In this study, we examine the differences in reported adverse events between 6 female- and 5 male-specific implantable devices from the Manufacturer and User Facility Device Experience (MAUDE) database from 1993 to 2018. Primary endpoints were injury type (life-threatening, disability, death) and the rate of device evaluation by the manufacturer. Proportions of valid entries across these variables were compared using either the Fisher exact test or χ2 test.

Results
Female-specific devices had higher rates of life-threatening outcomes (1.6% versus 0.3%, P < 0.001), disabilities (5.0% versus 4.3%, P < 0.001), and deaths (0.6% versus 0.1%, P < 0.001) compared with the male-specific devices. Of the 8159 devices that were evaluated by the manufacturer, 56% were female specific while 44% were male specific. Female-specific devices were evaluated far less frequently by the manufacturer (4.5% versus 38.2%, P < 0.001).

Conclusions
Increased adverse events reports for female-specific devices and associated high-grade complications necessitates improved postmarket surveillance.