bluuebunny/crossref_metadata_2025 huggingface dataset:
A collaborative study of the impact of N-nitrosamines presence and ARB recall on ARB utilization – results from IQVIA™ Disease Analyzer Germany
Authors: Hedenmalm Karin , Quinten Chantal , Kurz Xavier , Bradley Marie , Lee Hana , Eworuke Efe
Published: April 2023

Purpose

Regulators are increasingly concerned with  the impact of recalls on drug adherence. In 2018, N-nitrosamines impurities were detected in valsartan containing medical products. Concerned products were immediately recalled in July 2018 by regulatory agencies internationally. In Germany, recalls were issued for valsartan, losartan and irbesartan from July 2018 to March 2019. This study examined angiotensin II receptor blocker (ARB) utilization trends and switching patterns in Germany before and after July 2018.

Methods

Patients prescribed ARBs from January 2014 to June 2020 in general practices in Germany were included in a collaborative framework common protocol drug utilization study led by the US Food and Drug Administration. Trends in monthly and quarterly proportions of total ARB prescribing were analysed for individual ARBs using descriptive statistics and interrupted time series analysis. The rate of switching to an alternative ARB was analysed before and after the recalls.

Results

The proportion of valsartan prescriptions immediately decreased from 35.9 to 17.8% following the first recalls in July 2018, mirrored by an increased proportion for candesartan. Increased switching from valsartan to candesartan was observed. No increased switching was observed after losartan recalls, whereas for irbesartan, increased switching was observed 6–12 months after the last recall. Increased switching from ARBs to angiotensin-converting enzyme (ACE) inhibitors or ARB treatment discontinuations were not observed.

Conclusion

This study showed that patients were able to continue ARB treatment despite the July 2018–March 2019 recalls, although many patients needed to switch to an alternative ARB. The duration of the impact of ARB recalls appeared to be limited.
Aesthetic Surgery Advice and Counseling from Artificial Intelligence: A Rhinoplasty Consultation with ChatGPT
Authors: Xie Yi , Seth Ishith , Hunter-Smith David J. , Rozen Warren M. , Ross Richard , Lee Matthew
Published: April 2023

Background

ChatGPT is an open-source artificial large language model that uses deep learning to produce human-like text dialogue. This observational study evaluated the ability of ChatGPT to provide informative and accurate responses to a set of hypothetical questions designed to simulate an initial consultation about rhinoplasty.

Methods

Nine questions were prompted to ChatGPT on rhinoplasty. The questions were sourced from a checklist published by the American Society of Plastic Surgeons, and the responses were assessed for accessibility, informativeness, and accuracy by Specialist Plastic Surgeons with extensive experience in rhinoplasty.

Results

ChatGPT was able to provide coherent and easily comprehensible answers to the questions posed, demonstrating its understanding of natural language in a health-specific context. The responses emphasized the importance of an individualized approach, particularly in aesthetic plastic surgery. However, the study also highlighted ChatGPT’s limitations in providing more detailed or personalized advice.

Conclusion

Overall, the results suggest that ChatGPT has the potential to provide valuable information to patients in a medical context, particularly in situations where patients may be hesitant to seek advice from medical professionals or where access to medical advice is limited. However, further research is needed to determine the scope and limitations of AI language models in this domain and to assess the potential benefits and risks associated with their use.

Level of Evidence V

Observational study under respected authorities. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Daratumumab with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma patients – real world evidence analysis
Authors: Stork Martin , Spicka Ivan , Radocha Jakub , Minarik Jiri , Jelinek Tomas , Jungova Alexandra , Pavlicek Petr , Pospisilova Lenka , Sedlak Frantisek , Straub Jan , Pika Tomas , Knechtova Zdenka , Fidrichova Anna , Boichuk Ivanna , Sevcikova Sabina , Maisnar Vladimir , Hajek Roman , Pour Ludek
Published: April 2023

We performed real world evidence (RWE) analysis of daratumumab, lenalidomide and dexamethasone (Dara-Rd) versus lenalidomide and dexamethasone (Rd) treatment in relapsed/refractory multiple myeloma patients (RRMM). In total, 240 RRMM patients were treated with Dara-Rd from 2016 to 2022 outside of clinical trials in all major Czech hematology centers. As a reference, 531 RRMM patients treated with Rd were evaluated. Patients’ data were recorded in the Czech Registry of Monoclonal Gammopathies (RMG). Partial response (PR) or better response (ORR) was achieved in significantly more patients in Dara-Rd than in Rd group (91.2% vs. 69.9%; p < 0.001). The median progression free survival (PFS) was 26.9 months in the Dara-Rd and 12.8 months in the Rd group (p < 0.001). Median overall survival (OS) was not reached in the Dara-Rd compared to 27.2 months in the Rd group (p = 0.023). In patients with 1–3 previous treatment lines, there was significant PFS benefit of Dara-Rd compared to Rd (median PFS not reached vs. 13.2 months; p < 0.001). In patients with > 3 previous treatment lines, there was no significant PFS benefit of Dara-Rd treatment (7.8 months vs. 9.9 months; p = 0.874), similarly in patients refractory to PI + IMIDs (11.5 months vs. 9.2 months; p = 0.376). In RWE conditions, the median PFS in RRMM patients treated with Dara-Rd is shorter when compared to clinical trials. In heavily pretreated RRMM patients, efficacy of Dara-Rd treatment is limited; best possible outcomes of Dara-Rd are achieved in minimally pretreated patients.
Autoimmune Hemolytic Anemia in the Pediatric Age Group: The Egyptian Experience
Authors: Abdel-Salam Amina , Bassiouni Sherifa Tarek , Goher Alaa Magdi , Shafie Eman Shafik
Published: April 2023

Autoimmune hemolytic anemia (AIHA) is a common disease entity among adults; however, it is rare among the pediatric age group. Evidence is scarce regarding pediatric AIHA in the literature. The objective of this study is to assess the frequency of AIHA and describe the clinical and laboratory characteristics and treatment outcomes of a cohort of children with AIHA in Egypt. A retrospective study was conducted on 50 children with AIHA who were registered and followed up at the New Children’s Hospital in Cairo, Egypt, between January 2010 and January 2021. The study group comprised 60% females and 40% males. Their median age was 8.25 years. All patients showed low hemoglobin levels with a mean of 5.40 ± 1.34 g/dl and a median reticulocyte count of 10 (IQR: 8–15). Twelve (24%) patients were diagnosed with Evans syndrome, and a positive Coombs test was detected in 46 patients (92%). The frequency of primary AIHA was 40%, whereas it was 60% for secondary AIHA. The first line of therapy for acute attacks was high-dose IV steroids which responded well in 38 (76%) patients. Secondary AIHA was more common among our children (60%). AIHA is more prevalent in females (60%). The clinical and laboratory characteristics matched previous reports.
Scanning behaviour in ants: an interplay between random-rate processes and oscillators
Authors: Deeti Sudhakar , Cheng Ken , Graham Paul , Wystrach Antoine
Published: April 2023

At the start of a journey home or to a foraging site, ants often stop, interrupting their forward movement, turn on the spot a number of times, and fixate in different directions. These scanning bouts are thought to provide visual information for choosing a path to travel. The temporal organization of such scanning bouts has implications about the neural organisation of navigational behaviour. We examined (1) the temporal distribution of the start of such scanning bouts and (2) the dynamics of saccadic body turns and fixations that compose a scanning bout in Australian desert ants, Melophorus bagoti, as they came out of a walled channel onto open field at the start of their homeward journey. Ants were caught when they neared their nest and displaced to different locations to start their journey home again. The observed parameters were mostly similar across familiar and unfamiliar locations. The turning angles of saccadic body turning to the right or left showed some stereotypy, with a peak just under 45°. The direction of such saccades appears to be determined by a slow oscillatory process as described in other insect species. In timing, however, both the distribution of inter-scanning-bout intervals and individual fixation durations showed exponential characteristics, the signature for a random-rate or Poisson process. Neurobiologically, therefore, there must be some process that switches behaviour (starting a scanning bout or ending a fixation) with equal probability at every moment in time. We discuss how chance events in the ant brain that occasionally reach a threshold for triggering such behaviours can generate the results.
Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas
Authors: Wang Justin Z. , Patil Vikas , Liu Jeff , Dogan Helin , Tabatabai Ghazaleh , Yefet Leeor S. , Behling Felix , Hoffman Elgin , Bunda Severa , Yakubov Rebecca , Kaloti Ramneet , Brandner Sebastian , Gao Andrew , Cohen-Gadol Aaron , Barnholtz-Sloan Jill , Skardelly Marco , Tatagiba Marcos , Raleigh David R. , Sahm Felix , Boutros Paul C. , Aldape Kenneth ,   The International Consortium on Meningiomas (ICOM), Nassiri Farshad , Zadeh Gelareh
Published: April 2023

Homozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data of 1577 meningioma samples from 6 independent cohorts enriched for clinically aggressive meningiomas to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Homozygous CDKN2A/B deletions were identified in only 7.1% of cases but were associated with significantly poorer outcomes compared to tumors without these deletions. Heterozygous CDKN2A/B deletions were identified in 2.6% of cases and had similarly poor outcomes as those with homozygous deletions. Among tumors with intact CDKN2A/B (without a homozygous or heterozygous deletion), we found a distinct difference in outcome based on mRNA expression of CDKN2A, with meningiomas that had elevated mRNA expression (CDKN2Ahigh) having a significantly shorter time to recurrence. The expression of CDKN2A was independently prognostic after accounting for copy number loss and consistently increased with WHO grade and more aggressive molecular and methylation groups irrespective of cohort. Despite the discordant and mutually exclusive status of the CDKN2A gene in these groups, both CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycle pathways but at different checkpoints. High mRNA expression of CDKN2A was also associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. p16 immunohistochemistry could not reliably differentiate between meningiomas with and without CDKN2A deletions but appeared to correlate better with mRNA expression. These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications.
Postnatal genetic umbilical cord analysis for earliest possible detection of inherited hearing impairment
Authors: Ketterer Manuel Christoph , Birkenhäger Ralf , Beck Rainer , Arndt Susan , Aschendorff Antje , Kunze Mirjam
Published: April 2023

Introduction

The most common sensorineural disorder in humans is hearing impairment and approximately 60% of prelingual hearing disorders are genetic. Especially parents with a congenital deaf child want to know as early as possible whether their second born child has the same genetic defect or not. The aim of this study is to demonstrate that postnatal genetic umbilical cord analysis is both the earliest detection possibility and sufficient.

Methods

We included first born children with severe hearing impairment that underwent cochlear implantation. All included patients were analyzed genetically and exhibited mutations of either DFNB1 loci or SLC26A4 gene. Additionally, the umbilical cord of the sibling underwent genetic analysis to detect hereditary genetic mutations as early as possible.

Results

49 newborn children out of 22 families were included in this study. Genetic analysis revealed clinical relevant mutations in all first born children and in four siblings via umbilical cord analysis. All patients who have been diagnosed with a relevant genetic mutation that caused severe hearing impairment underwent hearing rehabilitation via cochlear implant surgery.

Conclusion

This study demonstrates the sufficient and early as possible detection of known genetically hearing disorders via umbilical cord analysis. In case of a known familial genetic hearing disorder, it is advisable to analyze newborn siblings for the corresponding genetic defect as soon as possible, to be able to plan and initiate clinical care for the patient as early as possible. It is also extremely important for the parents to obtain clear information about the auditory status of the newborn.
Minor head trauma in infants — how accurate is cranial ultrasound performed by trained radiologists?
Authors: Peter Claudia , Stranzinger Enno , Heverhagen Johannes T. , Keitel Kristina , Romano Fabrizio , Busch Jasmin D. , Slavova Nedelina
Published: April 2023

Correct management of infants after minor head trauma is crucial to minimize the risk to miss clinically important traumatic brain injury (ciTBI). Current practices typically involve CT or in-hospital surveillance. Cranial ultrasound (CUS) provides a radiation-free and fast alternative. This study examines the accuracy of radiologist-performed CUS to detect skull fracture (SF) and/or intracranial hemorrhage (ICH). An inconspicuous CUS followed by an uneventful clinical course would allow exclusion of ciTBI with a great certainty. This monocentric, retrospective, observational study analyzed CUS in infants (< 12 months) after minor head trauma at Bern University Children’s Hospital, between 7/2013 and 8/2020. The primary outcome was the sensitivity and specificity of CUS in detecting SF and/or ICH by comparison to the clinical course and to additional neuroimaging. Out of a total of 325 patients, 73% (n = 241) had a normal CUS, 17% (n = 54) were found with SF, and ICH was diagnosed in 2.2% patients (n = 7). Two patients needed neurosurgery and three patients deteriorated clinically during surveillance. Additional imaging was performed in 35 patients. The sensitivity of CUS was 93% ([0.83, 0.97] 95% CI) and the specificity 98% ([0.95, 0.99] 95% CI). All false-negative cases originated in missed SF without clinical deterioration; no ICH was missed.

  Conclusion: This study shows high accuracy of CUS in exclusion of SF and ICH, which can cause ciTBI. Therefore, CUS offers a reliable method of neuroimaging in infants after minor head trauma and gives reassurance to reduce the duration of in-hospital surveillance.

What is Known:

• Minor head trauma can cause clinically important traumatic brain injury in infants, and the management of these cases is a challenge for the treating physician.

• Cranial ultrasound (CUS) is regularly used in neonatology, but its accuracy after head trauma in infants is controversial.

What is New:

• CUS performed by a trained radiologist can exclude findings related to clinically important traumatic brain injury (ciTBI) with high sensitivity and specificity. It therefore offers reassurance in the management of infants after minor head trauma.
Unintended CRISPR-Cas9 editing outcomes: a review of the detection and prevalence of structural variants generated by gene-editing in human cells
Authors: Hunt John Murray Topp , Samson Christopher Allan , Rand Alex du , Sheppard Hilary M.
Published: April 2023

Genome editing using the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) gene-editing system (CRISPR-Cas) is a valuable tool for fundamental and applied research applications. Significant improvements in editing efficacy have advanced genome editing strategies into phase 3 human clinical trials. However, recent studies suggest that our understanding of editing outcomes has lagged behind the developments made in generating the edits themselves. While many researchers have analyzed on- and off-target events through the lens of small insertions or deletions at predicted sites, screens for larger structural variants (SVs) and chromosomal abnormalities are not routinely performed. Full and comprehensive validation of on- and off-target effects is required to ensure reproducibility and to accurately assess the safety of future editing applications. Here we review SVs associated with CRISPR-editing in cells of human origin and highlight the methods used to detect and avoid them.
Perfusionstechniken bei thorakoabdominellen Aortenaneurysmen
Authors: Schachner Thomas , Gratl Alexandra , Gorny Olaf , Enzmann Florian , Wipper Sabine H.
Published: April 2023

Die operative Behandlung thorakoabdomineller Aortenaneurysmen (TAAA) ist eine komplexe Prozedur und erfordert eine entsprechende Planung. Die TAAA werden entsprechend der Crawford-Klassifikation (Typen I bis V) eingeteilt. Typ-II-TAAA erfordern den ausgedehntesten Eingriff und weisen dementsprechend die höchste postoperative Morbidität und Mortalität auf. Die Perfusionsstrategie der Viszeralorgane und des Rückenmarks ist bei der operativen Versorgung der TAAA von zentraler Bedeutung. Die distale arterielle Perfusion, die selektive viszerale Perfusion und die additiven protektiven Maßnahmen mit Liquordrainage und hämodynamischem Management zur möglichst frühzeitigen Etablierung eines pulsatilen Flusses spielen dabei eine wesentliche Rolle. Die Techniken der extrakorporalen Zirkulation mit Herz-Lungen-Maschine oder Linksherzbypass werden mit ihren Vor- und Nachteilen diskutiert. Die Möglichkeiten zur viszeralen Organperfusion werden vorgestellt.
Mental health problems, stressful life events and new-onset urinary incontinence in primary school-age children: a prospective cohort study
Authors: Warne Naomi , Heron Jon , von Gontard Alexander , Joinson Carol
Published: April 2023

Emotional/behaviour problems and exposure to stressful life events are thought to contribute to new onset of urinary incontinence (UI) amongst children who have attained bladder control. However, very few prospective studies have examined these associations. We assessed whether mental health problems and stressful life events were associated with subsequent new onset in UI using multivariable logistic regression in a prospective UK cohort (n = 6408). Mothers provided information on their child’s symptoms of common mental disorders (Development and Wellbeing Assessment, 7 years), stressful life events (7–8 years) and wetting (day and night, 9 years). There was strong evidence that separation anxiety symptoms were associated with new-onset UI in the fully adjusted model (OR (95% CI) = 2.08 (1.39, 3.13), p < 0.001). Social anxiety, attention-deficit hyperactivity disorder and oppositional defiant disorder symptoms were associated with new-onset UI, but these associations attenuated following adjustment for child developmental level and earlier emotional/behaviour problems. There was weak evidence for a sex interaction with stressful life events (p = 0.065), such that females experiencing more stressful life events were at higher risk of new-onset UI (fully adjusted model OR (95% CI) = 1.66 (1.05, 2.61), p = 0.029), but there was no association in males (fully adjusted model OR (95% CI) = 0.87 (0.52, 1.47), p = 0.608). These results suggest that separation anxiety and stressful life events in girls may lead to an increase in UI.
A systematic review exploring characteristics of youth with severe and enduring mental health problems (SEMHP)
Authors: Bansema C. H. , Vermeiren R. R. J. M. , de Soet R. , van Ewijk H. , Nijland L. , Nooteboom L. A.
Published: April 2023

A small group of youth and emerging adults deals with severe and enduring mental health problems (SEMHP). Current mental health care struggles to recognize and treat this group timely and adequately, leaving these youth between the cracks of the system. A first step to improve care for this group is to gain a deeper understanding of the characteristics of youth with SEMHP. Therefore, this study aimed at reviewing current literature about this target group and what is known so far about their characteristics. We included 39 studies with a focus on youth aged 12–25 years with SEMHP. After critical appraisal, a content analysis and in-depth thematic analysis were conducted. According to the included studies, youth with SEMHP were characterized by severe distress and recurrent comorbid mental health problems, with pervasive suicidality. Further, underlying trauma, family conflicts, peer rejection, deep feelings of hopelessness, and psychosocial malfunctioning characterized SEMHP. It was described that for youth with SEMHP a pervasive pattern of dysfunction in multiple domains is present leading to a detrimental impact. Subsequently, this pattern exerts a reciprocal influence on the mental health problems, causing a vicious circle further worsening SEMHP. Our findings emphasize the need for a holistic approach and to look beyond the traditional classification system in order to meet the needs of these youth with wide-ranging comorbid mental health problems.
Different Cerrado Ecotypes Show Contrasting Soil Microbial Properties, Functioning Rates, and Sensitivity to Changing Water Regimes
Authors: Durán J. , Meira-Neto J. , Delgado-Baquerizo M. , Hamonts K. , Figueiredo V. , Enrich-Prast A. , Rodríguez A.
Published: April 2023

Soil moisture is among the most important factors regulating soil biodiversity and functioning. Models forecast changes in the precipitation regime in many areas of the planet, but how these changes will influence soil functioning, and how biotic drivers modulate such effects, is far from being understood. We evaluated the responses of C and N fluxes, and soil microbial properties to different soil water regimes in soils from the main three ecotypes of the world's largest and most diverse tropical savanna. Further, we explored the direct and indirect effects of changes in the ecotype and soil water regimes on these key soil processes. Soils from the woodland savanna showed a better nutritional status than the other ecotypes, as well as higher potential N cycling rates, N2O emissions, and soil bacterial abundance but lower bacterial richness, whereas potential CO2 emissions and CH4 uptake peaked in the intermediate savanna. The ecotype also modulated the effects of changes in the soil water regime on nutrient cycling, greenhouse gas fluxes, and soil bacterial properties, with more intense responses in the intermediate savanna. Further, we highlight the existence of multiple contrasting direct and indirect (via soil microbes and abiotic properties) effects of an intensification of the precipitation regime on soil C- and N-related processes. Our results confirm that ecotype is a fundamental driver of soil properties and functioning in the Cerrado and that it can determine the responses of key soil processes to changes in the soil water regime.
Interactive machine translation for the language modernization and spelling normalization of historical documents
Authors: Domingo Miguel , Casacuberta Francisco
Published: April 2023

Historical documents are an important part of our cultural heritage. Among other task related to their processing, it is important to modernize their language in order to make them accessible to a broader audience and to achieve an orthography consistency to reduce the linguistic variation inherent in them. Language modernization and spelling normalization have those goals in mind. However, they still have a long way to go. Thus, in order to help scholars generate error-free modernizations/normalizations when the quality is essential, we propose an interactive framework based on interactive machine translation. In this work, we deployed two different interactive protocols into these tasks. We evaluated our proposal under simulated environments, observing significant reductions of the human effort.
Etiology, diagnosis, treatment, and prevention of human papilloma virus-associated oropharyngeal squamous cell carcinoma
Authors: Shinomiya Hirotaka , Nibu Ken-ichi
Published: April 2023

Classical oropharyngeal squamous cell carcinoma (OPSCC) caused by alcohol consumption and smoking and HPV-associated OPSCC caused by human papillomavirus (HPV) infection have different etiologies, incidences, and prognoses. Therefore, the 8th American Joint committee on Cancer (AJCC) and Union for International Cancer Control (UICC) TNM classifications propose distinguishing HPV-associated OPSCC from classical OPSCC and classifying it as an independent disease. Therefore, this review provides an overview of HPV-associated OPSCC from the perspectives of epidemiology, carcinogenesis, development, diagnosis, treatment, and prevention. The incidence of HPV-associated OPSCC is increasing. Although HPV vaccination has been shown to be effective at reducing the incidence of cervical cancer, it is still unclear how it affects the incidence of HPV-associated OPSCC. Additionally, the prognosis of patients with HPV-associated OPSCC is extremely favorable compared to that of patients with classical OPSCC. Therefore, patients with HPV-associated OPSCC may undergo reduced-dose therapy, although attempts to reduce treatment intensity should be carefully planned to ensure they do not compromise oncological outcomes, and large-scale trials aimed at reducing treatment intensity are ongoing.
Pseudo-Kähler and pseudo-Sasaki structures on Einstein solvmanifolds
Authors: Conti Diego , Rossi Federico Alberto , Segnan Dalmasso Romeo
Published: April 2023

The aim of this paper is to construct left-invariant Einstein pseudo-Riemannian Sasaki metrics on solvable Lie groups. We consider the class of $$\mathfrak {z}$$
z
-standard Sasaki solvable Lie algebras of dimension $$2n+3$$

2
n
+
3

, which are in one-to-one correspondence with pseudo-Kähler nilpotent Lie algebras of dimension 2n endowed with a compatible derivation, in a suitable sense. We characterize the pseudo-Kähler structures and derivations giving rise to Sasaki–Einstein metrics. We classify $$\mathfrak {z}$$
z
-standard Sasaki solvable Lie algebras of dimension $$\le 7$$

≤
7

and those whose pseudo-Kähler reduction is an abelian Lie algebra. The Einstein metrics we obtain are standard, but not of pseudo-Iwasawa type.
External control arms for rare diseases: building a body of supporting evidence
Authors: Khachatryan Artak , Read Stephanie H , Madison Terri
Published: April 2023

Comparator arms in randomized clinical trials may be impractical and/or unethical to assemble in rare diseases. In the absence of comparator arms, evidence generated from external control studies has been used to support successful regulatory submissions and health technology assessments (HTA). However, conducting robust and rigorous external control arm studies is challenging and despite all efforts, residual biases may remain. As a result, regulatory and HTA agencies may request additional external control analyses so that decisions may be made based upon a body of supporting evidence.

This paper introduces external control studies and provides an overview of the key methodological issues to be considered in the design of these studies. A series of case studies are presented in which evidence derived from one or more external controls was submitted to regulatory and HTA agencies to provide support for the consistency of findings.
Development and evaluation of pharmacist-provided teach-back medication counselling at hospital discharge
Authors: O’Mahony E. , Kenny J. , Hayde J. , Dalton K.
Published: April 2023

Background

Pharmacists can use teach-back to improve patients’ understanding of medication; however, the evidence of its impact on patient outcomes is inconsistent. From the literature, there is no standardised way to provide pharmacist-delivered medication counselling at hospital discharge, with limited reporting on training.

Aim

To develop a standardised medication counselling procedure using teach-back at hospital discharge, and to evaluate feedback from patients and pharmacists on this initiative.

Method

A standardised intervention procedure was developed. Participating pharmacists (n = 9) were trained on teach-back via an online education module and watching a demonstration video created by the researchers. Pharmacists provided patients with discharge medication counselling utilising teach-back and a patient-friendly list of medication changes to take home. To obtain feedback, patients were surveyed within seven days of discharge via telephone and pharmacists answered an anonymous survey online.

Results

Thirty-two patients (mean age: 57 years; range: 19–91) were counselled on a mean 2.94 medications/patient with the mean counselling time as 23.6 min/patient. All patients responded to the survey, whereby 93.7% had increased confidence regarding medication knowledge and were satisfied with the counselling and the information provided. All pharmacist survey respondents (n = 8) agreed they were given adequate training and that teach-back was feasible to apply in practice.

Conclusion

This is the first study to evaluate patients’ views on pharmacist-provided teach-back medication counselling. With positive patient outcomes, a standardised procedure, and a comprehensive description of the training, this study can inform the development of discharge medication counselling utilising teach-back going forward.
Fairness in recommender systems: research landscape and future directions
Authors: Deldjoo Yashar , Jannach Dietmar , Bellogin Alejandro , Difonzo Alessandro , Zanzonelli Dario
Published: April 2023

Recommender systems can strongly influence which information we see online, e.g., on social media, and thus impact our beliefs, decisions, and actions. At the same time, these systems can create substantial business value for different stakeholders. Given the growing potential impact of such AI-based systems on individuals, organizations, and society, questions of fairness have gained increased attention in recent years. However, research on fairness in recommender systems is still a developing area. In this survey, we first review the fundamental concepts and notions of fairness that were put forward in the area in the recent past. Afterward, through a review of more than 160 scholarly publications, we present an overview of how research in this field is currently operationalized, e.g., in terms of general research methodology, fairness measures, and algorithmic approaches. Overall, our analysis of recent works points to certain research gaps. In particular, we find that in many research works in computer science, very abstract problem operationalizations are prevalent and questions of the underlying normative claims and what represents a fair recommendation in the context of a given application are often not discussed in depth. These observations call for more interdisciplinary research to address fairness in recommendation in a more comprehensive and impactful manner.
OncoVee™-MiniPDX-guided anticancer treatment for HER2-negative intermediate-advanced gastric cancer patients: a single-arm, open-label phase I clinical study
Authors: Zhang Baonan , Li Yuzhen , Zhu Xiaodan , Chen Zhe , Huang Xiaona , Gong Tingjie , Zheng Weiwang , Bi Zhenle , Zhu Chenyang , Qian Jingyi , Li Xiaoqiang , Jin Chunhui
Published: April 2023

Background

Chemotherapy is the main treatment strategy for patients with advanced HER2-negative gastric cancer (GC); yet, many patients do not respond well to treatment. This study evaluated the sensitivity of a mini patient-derived xenograft (MiniPDX) animal model in patients with HER2-negative intermediate-advanced GC.

Methods

In this single-arm, open-label clinical study, we consecutively recruited patients with HER2-negative advanced or recurrent GC from September 2018 to July 2021. Tumor tissues were subjected to MiniPDX drug sensitivity tests for screening individualized anti-tumor drugs; appropriate drug types or combinations were selected based on drug screening results. The primary endpoints were progression-free survival (PFS) and safety, and the secondary endpoints were overall survival (OS) and objective response rate (ORR).

Results

A total of 17 patients were screened, and 14 eligible patients were included.The median follow-up time was 9 (2–34) months. The median PFS time was 14.1 (2–34) months, the median OS time was 16.9 (2–34) months, ORR was 42.9% (6/14), and DCR was 92.9% (13/14). The most common treatment-related adverse events (TRAE) were fatigue (14 (100%)), anorexia (13 (93%)) and insomnia (12 (86%)), and the most common grade 3 or worse TRAE was fatigue (6 (43%)), and anorexia (6 (43%)). The occurrence rate of myelosuppression, nausea and vomiting, abnormal liver enzymes, and other grade 3–4 chemotherapy adverse reactions were relatively low, and no grade 5 treatment-related adverse events occurred.

Conclusion

Screening HER2-negative medium-advanced GC/GJC chemotherapy regimens and targeted drugs based on MiniPDX animal models showed good tumor activity and safety.
Repurposing the KCa3.1 Blocker Senicapoc for Ischemic Stroke
Authors: Lee Ruth D. , Chen Yi-Je , Nguyen Hai M. , Singh Latika , Dietrich Connor J. , Pyles Benjamin R. , Cui Yanjun , Weinstein Jonathan R. , Wulff Heike
Published: April 2023

Senicapoc, a small molecule inhibitor of the calcium-activated potassium channel KCa3.1, was safe and well-tolerated in clinical trials for sickle cell anemia. We previously reported proof-of-concept data suggesting that both pharmacological inhibition and genetic deletion of KCa3.1 reduces infarction and improves neurologic recovery in rodents by attenuating neuroinflammation. Here we evaluated the potential of repurposing senicapoc for ischemic stroke. In cultured microglia, senicapoc inhibited KCa3.1 currents with an IC50 of 7 nM, reduced Ca2+ signaling induced by the purinergic agonist ATP, suppressed expression of pro-inflammatory cytokines and enzymes (iNOS and COX-2), and prevented induction of the inflammasome component NLRP3. When transient middle cerebral artery occlusion (tMCAO, 60 min) was induced in male C57BL/6 J mice, twice daily administration of senicapoc at 10 and 40 mg/kg starting 12 h after reperfusion dose-dependently reduced infarct area determined by T2-weighted magnetic resonance imaging (MRI) and improved neurological deficit on day 8. Ultra-high-performance liquid chromatography/mass spectrometry analysis of total and free brain concentrations demonstrated sufficient KCa3.1 target engagement. Senicapoc treatment significantly reduced microglia/macrophage and T cell infiltration and activation and attenuated neuronal death. A different treatment paradigm with senicapoc started at 3 h and MRI on day 3 and day 8 revealed that senicapoc reduces secondary infarct growth and suppresses expression of inflammation markers, including T cell cytokines in the brain. Lastly, we demonstrated that senicapoc does not impair the proteolytic activity of tissue plasminogen activator (tPA) in vitro. We suggest that senicapoc could be repurposed as an adjunctive immunocytoprotective agent for combination with reperfusion therapy for ischemic stroke.
Is Race Associated with the Surgical Treatment for Benign Prostatic Hyperplasia? An Analysis of 30,000 Medicare Lives
Authors: Narang Gopal L. , Rojanasarot Sirikan , Cutone Ben , Humphreys Mitchell R.
Published: April 2023

Backgrounds

With an increased prevalence and burden of benign prostatic hyperplasia (BPH), effective and equitable treatment is a priority. Limited data exist evaluating treatment disparities for patients with BPH by race. This study examined the association between race and BPH surgical treatment rates among Medicare beneficiaries.

Methods

Medicare claims data were used to identify men newly diagnosed with BPH from January 1, 2010 through December 31, 2018. Patients were followed until their first BPH surgery, a diagnosis of prostate/bladder cancer, termination of Medicare enrollment, death, or end of study. Cox proportional hazards regression compared the likelihood of BPH surgery between men of different races (White vs. Black, Indigenous, and People of Color (BIPOC)), controlling for patients’ geographical region, Charlson comorbidity score, and baseline comorbidities.

Results

The study included 31,699 patients (13.7% BIPOC). BIPOC men had significantly lower BPH surgery rates (9.5% BIPOC vs. 13.4% White; p=0.02). BIPOC race was associated with a 19% lower likelihood of receiving BPH surgery than White race (HR, 0.81; 95% CI 0.70, 0.94). Transurethral resection of the prostate was the most common surgery for both groups (49.4% Whites vs. 56.8% BIPOC; p=0.052). A higher proportion of BIPOC men underwent procedures in inpatient settings compared to White men (18.2% vs. 9.8%; p<0.001).

Conclusions

Among a cohort of Medicare beneficiaries with BPH, there were notable treatment disparities by race. BIPOC men had lower rates of surgery than White men and were more likely to undergo procedures in the inpatient setting. Improving patient access to outpatient BPH surgical procedures may help address treatment disparities.
The Impact of COVID-19 Pandemic on Psychiatric Rehabilitation in Residential Facilities: Perspectives of Staff and Residents
Authors: Lasalvia Antonio , Bodini Luca , D’Astore Camilla , Gomez Francesca , Pesarin Alessia , Imperadore Giuseppe , Bonetto Chiara
Published: April 2023

The coronavirus pandemic imposed significant changes in the care of patients in psychiatric residential facilities, especially during lockdown periods. The aim of this study was to assess the impact of the pandemic on patients and staff of psychiatric residential facilities (RFs). This cross-sectional survey was conducted between 30 June and 30 July 2021 and involved 31 RFs located in the province of Verona (Italy). In total, 170 staff members and 272 residents participated in this study. Staff showing clinically significant symptoms of anxiety, depression and burnout were, respectively, 7.7%, 14.2% and 6%. Staff were concerned about the risk that COVID-19 infection might spread among residents (67.6%) and that residents could not receive an acceptable service due to service reconfiguration because of the pandemic (50.3%). Residents found it very unpleasant not to be permitted to attend family members (85.3%), and not to be allowed to engage in outdoor activities due to the restrictions (84%). Both staff and residents agree that the main problematic areas for the residents was the interdiction to meet family members or friends and the interdiction to outdoor activities, whereas problems related to the COVID-19 infection were considered by the staff members as more frequently problematic than reported by residents. The COVID-19 pandemic had a significant impact on the rehabilitation care and recovery journeys of the residents of psychiatric RFs. Therefore, sustained, and careful attention is needed to ensure that the rehabilitation needs of people with severe mental disorders are not neglected in time of pandemics.
Market-Engaging Institutions: The Rule of Law, Resilience and Responsiveness in an Era of Institutional Flux
Authors: Ramanujam Nandini , Farrington Francesca
Published: April 2023

This article analyses the institutional conditions required to support a strategic state in being responsive to the changing demands of a market-economy, whilst maintaining a credible commitment to long-term policy goals. This article identifies a key pillar of a market economy that we believe is crucial to promoting inclusive economic growth; we term these institutionsmarket-engaging institutions.We propose that market-engaging institutions may form a bridge between the flexibility required by a dynamic market economy and the stability demanded by the rule of law. We define market-engaging institutions as those institutions that facilitate greater political participation for marginalized groups, manage technological disruptions, and support human capital formation. Examples include social partnership agreements, collective bargaining coverage, trade union membership, education and training services, and research and development programmes. We suggest that mobilizing these institutions necessitates credible commitment. Further, we argue that through its commitment to the non-arbitrary administration of general rules the rule of law is an essential condition for signalling the state’s credible commitment. However, at times the requirement for the state to be flexible to the changing needs of market actors may conflict with the rule of law’s demand for constancy and stability. This article examines the delicate balancing act required to sustain a strategic, responsive, and credible state in an era of institutional flux.
Diverging destinies: changing trends of induced abortion in China
Authors: Jin Yongai , Hu Wenbo
Published: April 2023

In the era of the second demographic transition, “diverging destinies” theory states that women with the most economic opportunities often obtain gains while women with the least economic opportunities suffer from losses. Using nationally representative data from the 2017 China Fertility Survey, we attempted to examine if diverging destinies theory can explain differences in the incidence of induced abortion among women with differing economic opportunities. We found that women with good economic opportunities (i.e., well-educated and holding urbanhukou) were more likely to have induced abortions between 1980 and 2010 and less likely to do so between 2015 and 2017. Moreover, younger cohorts were far more likely to have induced abortions at a younger age and before marriage. These findings provide supportive evidence for diverging destinies in induced abortion scenarios in China. We thus advocate that sexual and reproductive health policy making shows an overarching concern for the interests of disadvantaged groups.
Firm policies and employees’ participation in conversation about their employer on social media
Authors: Del Bosco Barbara , Mazzucchelli Alice , Chierici Roberto
Published: April 2023

This paper studies the relationship between firms’ strategy and policies in regard to social media and their employees’ propensity to endorse them by using their personal social media accounts. In particular, the study investigates the effect of employees’ perception of firms’ social media strategy and initiatives aimed at influencing employees’ behavior on their personal social media profiles (communication of policies on the use of social media, training programs, and encouragement to join social media conversations regarding the firm). Based on the responses of 224 employees who use their personal accounts to talk about their firms, findings show that employees’ positive evaluation of firms’ social media strategy and firms’ explicit encouragement are positively associated with employees’ propensity to endorse their firms on social media. Moreover, results reveal the moderating effect of employees’ frequency of social media use on the relationship between communication of social media policies and the employees’ propensity to endorse their firm, as well as on the relationship between training programs and the propensity to endorse. This study provides evidence of the influence of firms’ social media activity and policies on the willingness of employees to promote and advocate their employers using their personal accounts, with theoretical and practical implications. The research also suggests that the effectiveness of firms’ policies may differ according to the frequency of social media usage by employees.
When is industry ‘sustainable’? The economics of institutional variety in a pandemic
Authors: Srinivas Smita
Published: April 2023

Industrialising economies today are characterised by a multi-level heterogeneity of customs, norms, guidelines, standards, regulations and other laws that provide the broad scaffolding and the technical context for industrial activity. This institutional variety (IV) leads to combinatorial challenges about which institutions are mixed and matched as technologies and sectors evolve. Gaps in evolutionary political economy and evolutionary institutional methods should explain when variety is ‘better’ for industrial development. Two health industry cases, oxygen production and Ayurveda, have come into the pandemic spotlight under high demand and high uncertainty, by patients, state, firms, experts and other stakeholders. Both cases reflect markedly different types of institutional variety with implications for manufacturing and services. A debate of sustainable industrial policies (SIPs) thus requires attention to institutional variety (IV) and a future agenda on healthcare.
Prevalence of Extended-Spectrum β-Lactamases in Multidrug-Resistant Klebsiella pneumoniae Isolates in Jordanian Hospitals
Authors: Al-Sheboul Suhaila A. , Al-Madi Ghina S. , Brown Brent , Hayajneh Wail A.
Published: April 2023

The increase in the prevalence of infections caused by certain bacteria, such as Klebsiella pneumonia (K. pneumoniae), is a global health concern. Bacterial production of an enzyme called extended-spectrum beta-lactamase (ESBL) can generate resistance to antimicrobial therapeutics. Therefore, between 2012 and 2013, we investigated K. pneumoniae that produce ESBLs with the prevalence of individual genes including blaSHV, blaCTX-M, blaTEM, and blaOXA isolated from clinical samples. A total of 99 variable diagnostic samples including blood from hematological malignancies (n = 14) or other clinical sources including sputum, pus, urine, and wound (n = 85) were analyzed. All samples' bacterial type was confirmed and their susceptibility to antimicrobial agents was established. Polymerase chain reaction (PCR) amplification was carried out to ascertain presence of specific genes that included blaSHV, blaCTX-M, blaTEM, and blaOXA. Plasmid DNA profiles were determined to assess significance between resistance to antimicrobial agents and plasmid number. It was found that among non-hematologic malignancy isolates, the highest rate of resistance was 87.9% to imipenem, with lowest rate being 2% to ampicillin. However, in hematologic malignancy isolates, the highest microbial resistance was 92.9% to ampicillin with the lowest rate of resistance at 28.6% to imipenem. Among collected isolates, 45% were ESBL-producers with 50% occurrence in hematologic malignancy individuals that were ESBL-producers. Within ESBL-producing isolates from hematologic malignancy individuals, blaSHV was detected in 100%, blaCTX-M in 85.7%, and blaTEM and blaOXA-1 at 57.1% and 27.1%, respectively. In addition, blaSHV,blaCTX-M, and blaOXA were found in all non-hematological malignancy individuals with blaTEM detected in 55.5% of samples. Our findings indicate that ESBLs expressing blaSHV and blaCTX-M genes are significantly prevalent in K. pneumoniae isolates from hematologic malignancy individuals. Plasmid analysis indicated plasmids in isolates collected from hematological malignancy individuals. Furthermore, there was a correlation between resistance to antimicrobial agents and plasmids within two groups analyzed. This study indicates an increase in incidence of K. pneumoniae infections displaying ESBL phenotypes in Jordan.