bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why is the Implementation of Beta-Lactam Therapeutic Drug Monitoring for the Critically Ill Falling Short? A Multicenter Mixed-Methods Study
Authors: Barreto Erin F. , Chitre Pooja N. , Pine Kathleen H. , Shepel Kathryn K. , Rule Andrew D. , Alshaer Mohammad H. , Abdul Aziz Mohd Hafiz , Roberts Jason A. , Scheetz Marc H. , Ausman Sara E. , Moreland-Head Lindsay N. , Rivera Christina G. , Jannetto Paul J. , Mara Kristin C. , Boehmer Kasey R. 
Published: April 2023

Background:
Beta-lactam therapeutic drug monitoring (BL TDM; drug level testing) can facilitate improved outcomes in critically ill patients. However, only 10%–20% of hospitals have implemented BL TDM. This study aimed to characterize provider perceptions and key considerations for successfully implementing BL TDM.

Methods:
This was a sequential mixed-methods study from 2020 to 2021 of diverse stakeholders at 3 academic medical centers with varying degrees of BL TDM implementation (not implemented, partially implemented, and fully implemented). Stakeholders were surveyed, and a proportion of participants completed semistructured interviews. Themes were identified, and findings were contextualized with implementation science frameworks.

Results:
Most of the 138 survey respondents perceived that BL TDM was relevant to their practice and improved medication effectiveness and safety. Integrated with interview data from 30 individuals, 2 implementation themes were identified: individual internalization and organizational features. Individuals needed to internalize, make sense of, and agree to BL TDM implementation, which was positively influenced by repeated exposure to evidence and expertise. The process of internalization appeared more complex with BL TDM than with other antibiotics (ie, vancomycin). Organizational considerations relevant to BL TDM implementation (eg, infrastructure, personnel) were similar to those identified in other TDM settings.

Conclusions:
Broad enthusiasm for BL TDM among participants was found. Prior literature suggested that assay availability was the primary barrier to implementation; however, the data revealed many more individual and organizational attributes, which impacted the BL TDM implementation. Internalization should particularly be focused on to improve the adoption of this evidence-based practice.
TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain
Authors: Aloi Vincenzo Davide , Pinto Sílvia João Poseiro Coutinho , Van Bree Rita , Luyten Katrien , Voets Thomas , Vriens Joris 
Published: April 2023

Abstract
Chemotherapy-induced peripheral neuropathic pain (CIPNP) is an adverse effect observed in up to 80% of patients of cancer on treatment with cytostatic drugs including paclitaxel and oxaliplatin. Chemotherapy-induced peripheral neuropathic pain can be so severe that it limits dose and choice of chemotherapy and has significant negative consequences on the quality of life of survivors. Current treatment options for CIPNP are limited and unsatisfactory. TRPM3 is a calcium-permeable ion channel functionally expressed in peripheral sensory neurons involved in the detection of thermal stimuli. Here, we focus on the possible involvement of TRPM3 in acute oxaliplatin-induced mechanical allodynia and cold hypersensitivity. In vitro calcium microfluorimetry and whole-cell patch-clamp experiments showed that TRPM3 is functionally upregulated in both heterologous and homologous expression systems after acute (24 hours) oxaliplatin treatment, whereas the direct application of oxaliplatin was without effect. In vivo behavioral studies using an acute oxaliplatin model for CIPNP showed the development of cold and mechano hypersensitivity in control mice, which was lacking in TRPM3 deficient mice. In addition, the levels of protein ERK, a marker for neuronal activity, were significantly reduced in dorsal root ganglion neurons derived from TRPM3 deficient mice compared with control after oxaliplatin administration. Moreover, intraperitoneal injection of a TRPM3 antagonist, isosakuranetin, effectively reduced the oxaliplatin-induced pain behavior in response to cold and mechanical stimulation in mice with an acute form of oxaliplatin-induced peripheral neuropathy. In summary, TRPM3 represents a potential new target for the treatment of neuropathic pain in patients undergoing chemotherapy.
Behavioral cancer pain intervention dosing: results of a Sequential Multiple Assignment Randomized Trial
Authors: Somers Tamara J. , Winger Joseph G. , Fisher Hannah M. , Hyland Kelly A. , Davidian Marie , Laber Eric B. , Miller Shannon N. , Kelleher Sarah A. , Plumb Vilardaga Jennifer C. , Majestic Catherine , Shelby Rebecca A. , Reed Shelby D. , Kimmick Gretchen G. , Keefe Francis J. 
Published: April 2023

Abstract
Behavioral pain management interventions are efficacious for reducing pain in patients with cancer. However, optimal dosing of behavioral pain interventions for pain reduction is unknown, and this hinders routine clinical use. A Sequential Multiple Assignment Randomized Trial (SMART) was used to evaluate whether varying doses of Pain Coping Skills Training (PCST) and response-based dose adaptation can improve pain management in women with breast cancer. Participants (N = 327) had stage I-IIIC breast cancer and a worst pain score of >5/10. Pain severity (a priori primary outcome) was assessed before initial randomization (1:1 allocation) to PCST-Full (5 sessions) or PCST-Brief (1 session) and 5 to 8 weeks later. Responders (>30% pain reduction) were rerandomized to a maintenance dose or no dose and nonresponders (<30% pain reduction) to an increased or maintenance dose. Pain severity was assessed again 5 to 8 weeks later (assessment 3) and 6 months later (assessment 4). As hypothesized, PCST-Full resulted in greater mean percent pain reduction than PCST-Brief (M [SD] = −28.5% [39.6%] vs M [SD]= −14.8% [71.8%]; P = 0.041). At assessment 3 after second dosing, all intervention sequences evidenced pain reduction from assessment 1 with no differences between sequences. At assessment 4, all sequences evidenced pain reduction from assessment 1 with differences between sequences (P = 0.027). Participants initially receiving PCST-Full had greater pain reduction at assessment 4 (P = 0.056). Varying PCST doses led to pain reduction over time. Intervention sequences demonstrating the most durable decreases in pain reduction included PCST-Full. Pain Coping Skills Training with intervention adjustment based on response can produce sustainable pain reduction.
Impacts of Culture on Perceptions of Intimate Partner Violence Among Fijian Indian Women in the United States
Authors: Prasad Shayal S. , Bidwell Julie T. , Murray-García Jann L. 
Published: April 2023

ABSTRACT

Introduction
South Asian women are at a higher risk for experiencing intimate partner violence (IPV) in the United States. Fijian Indian (FI) women are part of the diverse South Asian diaspora; however, there are no published data on their experience with IPV. This phenomenological study (a) examined if FI culture influences how women define, experience, and seek help for IPV and (b) identified impacts these themes have on FI women's IPV-related help-seeking, behaviors in regard to U.S. health systems and law enforcement.

Methods
Ten FI women in California, 18 years and older, who either were born in Fiji or had parents born in Fiji, were recruited through convenience and snowball sampling. Semistructured interviews took place either face-to-face or via Zoom. Transcribed interview data underwent reflective thematic analysis by two members of the research team.

Results
Normalizing and silencing of IPV events are bolstered by cultural practices of (a) familism/collectivism that ask women to prioritize family intactness over their own emotional and physical safety, (b) traditional patriarchal gender roles, (c) threats of shame and judgment within the community, and (d) the gendered hierarchy tenets of some forms of Hinduism. FI women are more inclined to seek help for IPV from within versus outside the family, with healthcare providers and law enforcement described as women's last choices for assistance.

Conclusions
Although a small and regionalized immigrant community, this study of FI women reflects the importance of health and human service providers' understanding of the histories and cultural nuances of the local immigrant populations they serve.
Development of the Acute Care Nurse Practitioner Competencies Scale: An Exploratory and Confirmatory Factor Analysis
Authors: TSAY Shiow-Luan , KAU Kevin , HUANG Sheng-Shiung , CHANG Shu-Chen 
Published: April 2023

ABSTRACT

Background
Nurse practitioners (NPs) play a vital role in healthcare, particularly in acute care settings in Taiwan. The professional competencies of NPs are essential for providing safe and effective care to patients. To date, no measurement tool is available for assessing the clinical competencies of NPs in acute care practices.

Purpose
The aim of this study was to develop and investigate the psychometric properties of the Acute Care Nurse Practitioner Competencies Scale (ACNPCS).

Methods
Mixed-method research was employed using samples of experienced NPs. First, we used a focus group of seven experienced NPs who worked for medical centers, community hospitals, and regional hospitals to identify clinical competencies content. Second, we implemented consensus validation using two rounds of the Delphi study and revised it to a 39-item ACNPCS. Third, we conducted content validity with nine NP experts and modified the competency content to 36 items. Finally, we conducted a national survey of 390 NPs from 125 hospitals to determine the extent to which the NP competency content relates to their clinical practice. To examine the reliability of the tool, we tested the internal consistency reliability and test–retest reliability. Exploratory factor analysis, confirmatory factor analysis, and known-group validity were used to test the construct validity of the ACNPCS.

Results
The Cronbach's alpha coefficient for the overall scale was .92, with subscale coefficients ranging from .71 to .89. Test–retest reliability showed the two scores of the ACNPCS on the two occasions tested to be highly correlated (r = .85, p < .001). Exploratory factor analysis revealed that the scale had six factors: providing healthcare, evaluating care, collaboration, education, care quality/research, and leadership/professionalism. Factor loadings for each factor item ranged from .50 to .80 and explained 72.53% of the total variance in the NPs' competencies. Confirmatory factor analysis indicated that the six-factor model showed satisfactory model fit (χ2 = 780.54, p < .01), and the fit indices met the standards for adequate fit (goodness-of-fit index = .90, comparative fit index = .98, Tucker–Lewis index = .97, root mean square error of approximation = .04, and standardized root mean residual = .04). Known-group validity revealed that the total scores for novice NPs differed significantly from those of expert NPs in terms of the competencies (t = 3.26, p < .001). These results validated the psychometric soundness of the newly developed ACNPCS.

Conclusions
The newly developed ACNPCS exhibited satisfactory reliability and validity, supporting the use of the ACNPCS as a tool to assess the clinical competencies of NPs in acute care settings.
A Molecular Landscape of Stress Urinary Incontinence in Women Suggests an Important Role of Beta-Catenin Signaling in Disease Etiology
Authors: Post Wilke M. , Widomska Joanna , Oosterwijk Egbert , De Witte Ward , Coenen Marieke J. H. , Janssen Dick A. W. , Martens Frank , Cartwright Rufus , Minassian Vatche A. , Penney Kathryn L. , Thomas Laurent F. , Skogholt Anne H. , Stafne Signe N. , Hveem Kristian , Kluivers Kirsten B. , Poelmans Geert 
Published: April 2023

Purpose:
Stress urinary incontinence (SUI) represents a major health burden in women, but a thorough understanding of the underlying molecular mechanisms is lacking. Our aim was to further elucidate these mechanisms to ultimately find new treatments.

Materials and Methods:
This study integrated the most significant genes from 4 genome-wide association studies (GWASs) of SUI in women with other genetic, expression, and/or functional evidence from the literature into a molecular landscape. A network enrichment analysis of the top SUI GWAS genes was conducted, followed by an extensive literature search to identify interactions between the proteins encoded by the GWAS genes and proteins/molecules implicated in SUI through other evidence.

Results:
In total, 188 GWAS genes were used for network enrichment analysis that yielded 12 networks, of which 8 were overlapping, with beta-catenin as the central protein. Based on this finding and our literature search, we built a molecular landscape of female SUI that centers on beta-catenin signaling. Other important functional landscape themes are epithelial-mesenchymal transition, NANOG signaling, and female sex hormone signaling.

Conclusions:
The molecular landscape of female SUI that we built based on genetic data provides novel molecular insights that may be instrumental for better understanding the etiology of SUI and developing novel SUI treatments.
The role of the electroencephalogram and evoked potentials after cardiac arrest
Authors: Sandroni Claudio , Grippo Antonello , Westhall Erik 
Published: April 2023

Purpose of review
In comatose cardiac arrest survivors, the electroencephalogram (EEG) is the most widely used test to assess the severity of hypoxic–ischemic brain injury (HIBI) and guide antiseizure treatment. However, a wide variety of EEG patterns are described in literature. Moreover, the value of postarrest seizure treatment is uncertain. Absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) are a specific predictor of irreversible HIBI. However, the prognostic significance of the N20 amplitude is less known.

Recent findings
The increasing adoption of standardized EEG pattern classification identified suppression and burst-suppression as ‘highly-malignant’ EEG patterns, accurately predicting irreversible HIBI. Conversely, continuous normal-voltage EEG is a reliable predictor of recovery from postarrest coma. A recent trial on EEG-guided antiseizure treatment in HIBI was neutral but suggested potential benefits in specific subgroups. A prognostic approach based on the amplitude rather than on the presence/absence of the N20 SSEP wave recently showed greater sensitivity for poor outcome prediction and added potential for predicting recovery.

Summary
Standardized EEG terminology and quantitative approach to SSEP are promising for improving the neuroprognostic accuracy of these tests. Further research is needed to identify the potential benefits of antiseizure treatment after cardiac arrest.
In-hospital cardiac arrest
Authors: Soar Jasmeet 
Published: April 2023

Purpose of review
To describe our knowledge about in-hospital cardiac arrest (IHCA) including recent developments.

Recent findings
Improving trends in IHCA outcomes appear to have stalled or reversed since the COVID-19 pandemic. There are disparities in care based on patient sex, ethnicity and socioeconomic status that need to be tackled. The increased use of emergency treatment plans that include do-not attempt cardiopulmonary resuscitation recommendations will help to decrease the number of resuscitation attempts. System approaches and strong local leadership through resuscitation champions can improve patient outcomes.

Summary
In-hospital cardiac arrest is a global health problem with a 25% survival in high-income settings. There remain significant opportunities to both decrease the incidence of, and outcomes from IHCA.
Devices for assessing microcirculation
Authors: Edul Vanina K. , Gutierrez Facundo J. 
Published: April 2023

Purpose of review
Devices for assessing microcirculation at the bedside have been a technological breakthrough in the critical care field. Thanks to this technology, a large body of scientific evidence has highlighted the relevance of microcirculatory disruptions during critical illness. The goal of this review is to analyze the current knowledge concerning microcirculation monitoring, mainly focused on clinically available devices.

Recent findings
New evidence in oxygenation monitoring, advances in hand-held vital microscopes, and improvements in laser-based techniques ensure the possibility of detecting poor resuscitation, testing vascular reactivity, and assessing the effect of therapy during shock and resuscitation.

Summary
Currently, there are several methods for microcirculatory monitoring. To properly apply and correctly interpret the information they provide, clinicians should know the fundamental principles and the strengths and weaknesses of the clinically available devices.
A Comparison of Etiologies and Characteristics of Solitary Versus Synchronous Pancreatic Masses Undergoing Endoscopic Ultrasound-Guided Biopsy
Authors: Levine Irving , Suchman Kelly , Patel Zankesh , Ghani Maham , Hussein Karim , Ramada Michael , Cubillan Mark Patrick , Garg Shashank , Trindade Arvind J. 
Published: April 2023

Objectives
Pancreatic mass lesions are often solitary, although rarely synchronous pancreatic masses are encountered. No study has compared synchronous lesions with solitary lesions in the same population. The aim of the present study was to determine the prevalence, clinical, radiographic, and histologic findings of multiple pancreatic masses on consecutive patients undergoing endoscopic ultrasound (EUS) for pancreatic mass lesion.

Methods
All patients undergoing EUS for pancreatic mass lesions with histologic sampling over a 5-year span were identified. Charts were abstracted for demographics, medical history, radiographic findings, EUS findings, and histology and were reviewed.

Results
A total of 646 patients were identified, of which 27 patients (4.18%) had more than 1 pancreatic mass on EUS or cross-sectional imaging. The 2 groups were comparable with each other in terms of demographic factors and medical history. The 2 cohorts were comparable in location of the largest pancreas lesion and EUS characteristics. Patients with synchronous mass lesions were more likely to have metastatic lesions (P = 0.01). No other differences in histology were noted between the 2 groups.

Conclusions
Patients with multiple pancreatic mass lesions were more likely to have metastatic lesions compared with patients with solitary lesions.
A Real-World Observational Study of the Use and Associated Costs of Treating Neuroendocrine Tumors With Somatostatin Analogs in Canada
Authors: Cheung Winson Y. , LaForty Callahan , Liovas Anna , McKechnie Heather , Loree Jonathan M. 
Published: April 2023

Objectives
Somatostatin analogs (SSAs; lanreotide autogel and octreotide long-acting release) are used to treat neuroendocrine tumors; however, factors that influence SSA use are unclear.

Methods
This real-world, observational study collected data from private/public pharmacy claims for patients using SSAs in Canada. Data relating to dosing regimens, injection burden, treatment persistence, and costs were retrospectively analyzed for treatment-naive patients.

Results
Overall, 1545 patients were included in the analysis of dosing regimens, 908 for injection burden, 453 for treatment persistence, and 903 for treatment-associated costs. Compared with lanreotide, treatment with octreotide long-acting release was more likely associated with treatment above the maximum recommended dose (odds ratio, 16.2; 95% confidence interval, 4.3–136.2; P < 0.0001), higher weighted average long-acting SSA injection burden (13.4 vs 12.5, P < 0.0001), and a higher number of rescue medication claims per patient (0.22 vs 0.03, P < 0.0001). Treatment with lanreotide autogel was associated with greater treatment persistence (hazard ratio, 0.58; 95% confidence interval, 0.42–0.80; P = 0.001) and lower mean annual costs of treatment than octreotide long-acting release (Canadian dollars $27,829.35 vs $31,255.49; P < 0.0001).

Conclusions
These findings provide valuable insight into SSA use in clinical settings and may inform treatment selection.
Does Chronic Use of High Dose Proton Pump Inhibitors Increase Risk for Pancreatic Cancer?
Authors: Huber Matthew A. , Nadella Sandeep , Cao Hong , Kallakury Bhaskar , Tucker Robin D. , Gay Martha D. , Shivapurkar Narayan , Edmondson Elijah F. , Yue Yuanzhen , Dou Wenyu , Fang Hong-Bin , Smith Jill P. 
Published: April 2023

Objectives
To analyze whether use of proton pump inhibitors increase the risk for pancreatic cancer in a mouse model and human clinical cohorts.

Methods
p48-Cre/LSL-KrasG12D mice that develop precancerous pancreatic intraepithelial neoplasia (PanINs) were treated with low- or high-dose proton pump inhibitors (PPIs) orally for 1 and 4 months. The mechanism for the cholecystokinin receptor 2 (CCK-2R) activation was investigated in vitro. Two resources were employed to analyze the risk of pancreatic cancer in human subjects with PPI use.

Results
Serum gastrin levels were increased 8-fold (P < 0.0001) in mice treated with chronic high-dose PPIs, and this change correlated with an increase (P = 0.02) in PanIN grade and the development of microinvasive cancer. The CCK-2R expression was regulated by microRNA-148a in the p48-Cre/LSL-KrasG12D mice pancreas and in human pancreatic cancer cells in vitro. Proton pump inhibitor consumption in human subjects was correlated with pancreatic cancer risk (odds ratio, 1.54). A validation analysis conducted using the large-scale United Kingdom Biobank database confirmed the correlation (odds ratio, 1.9; P = 0.00761) of pancreatic cancer risk with PPI exposure.

Conclusions
This investigation revealed in both murine models and human subjects, PPI use is correlated with a risk for development of pancreatic cancer.
Defining the Optimal Duration of Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma
Authors: Puleo Amanda , Malla Midhun , Boone Brian A. 
Published: April 2023

Abstract
Despite recent advances, pancreatic ductal adenocarcinoma (PDAC) continues to be associated with dismal outcomes, with a cure evading most patients. While historic treatment for PDAC has been surgical resection followed by 6 months of adjuvant therapy, there has been a recent shift toward neoadjuvant treatment (NAT). Several considerations support this approach, including the characteristic early systemic spread of PDAC, and the morbidity often surrounding pancreatic resection, which can delay recovery and preclude patients from starting adjuvant treatment. The addition of NAT has been suggested to improve margin-negative resection rates, decrease lymph node positivity, and potentially translate to improved survival. Conversely, complications and disease progression can occur during preoperative treatment, potentially eliminating the chance of curative resection. As NAT utilization has increased, treatment durations have been found to vary widely between institutions with an optimal duration remaining undefined. In this review, we assess the existing literature on NAT for PDAC, reviewing treatment durations reported across retrospective case series and prospective clinical trials to establish currently used approaches and seek the optimal duration. We also analyze markers of treatment response and review the potential for personalized approaches that may help clarify this important treatment question and move NAT toward a more standardized approach.