bluuebunny/crossref_metadata_2025 huggingface dataset:
The diagnostic value of urinary N-terminal fragment of titin for skeletal muscle damage in idiopathic inflammatory myopathy
Authors: Sun Jianhong , Ye Sheng , Yin Geng , Xie Qibing
Published: March 2023

Objectives

N-terminal fragment of titin (N-titin) is a marker of sarcomere damage in striated muscles; however, its value in patients with IIM (idiopathic inflammatory myopathy) is unclear. This study aimed to investigate the diagnostic value of N-titin for skeletal muscle damage in patients with IIM.

Methods

Urine samples from 62 patients with IIM, 59 patients with other CTD diseases, and 29 healthy controls were collected to detect N-titin by ELISA assays. Clinical features and laboratory data were all included in logistic regression analysis to obtain the independent predictive factor for skeletal muscle damage.

Results

Urinary N-titin level of the IIM group [168.3 (19.0, 1279.0) pmol/mg cr] was significantly higher than that in CTD controls [2.80 (1.53, 3.60)] and healthy controls [1.83 (1.09, 2.95)] (P < 0.001). IIM patients with skeletal muscle injury had a significantly higher level of urinary N-titin [1001.0, (181.8, 1977.0)] than those without [9.3, (5.8, 23.9)] (P < 0.001). The N-titin level was strongly correlated with CK (r = 0.907, P < 0.001) and muscle disease activity assessment scores by Spearman correlation analysis. After adjusting for the anti-MDA5 antibody and cardiac troponin T, N-titin was shown to independently predict skeletal muscle damage in patients with IIM (odds ratio = 1.035, 95% CI: 1.002, 1.069, P = 0.039). The cut-off value of urinary N-titin to diagnose skeletal muscle damage was 89.9 pmol/mg Cr, with a sensitivity of 87.8% and a specificity of 100% (AUC = 0.971, 95% CI: 0.938, 1.000, P < 0.001).

Conclusion

Urinary N-titin is a non-invasive and independent predictive factor for determining skeletal muscle damage in patients with IIM.
Genetics of longitudinal kidney function in children and adults with systemic lupus erythematosus
Authors: Tang Thai-Son , Liao Fangming , Webber Declan , Gold Nicholas , Cao Jingjing , Dominguez Daniela , Gladman Dafna , Knight Andrea , Levy Deborah M , Ng Lawrence , Paterson Andrew D , Touma Zahi , Urowitz Murray B , Wither Joan , Silverman Earl D , Pullenayegum Eleanor M , Hiraki Linda T
Published: March 2023

Objectives

Genome-wide association studies (GWAS) have identified loci associated with estimated glomerular filtration rate (eGFR). Few LN risk loci have been identified to date. We tested the association of SLE and eGFR polygenic risk scores (PRS) with repeated eGFR measures from children and adults with SLE.

Methods

Patients from two tertiary care lupus clinics that met ≥4 ACR and/or SLICC criteria for SLE were genotyped on the Illumina MEGA or Omni1-Quad arrays. PRSs were calculated for SLE and eGFR, using published weighted GWA-significant alleles. eGFR was calculated using the CKD-EPI and Schwartz equations. We tested the effect of eGFR- and SLE-PRSs on eGFR mean and variance, adjusting for age at diagnosis, sex, ancestry, follow-up time, and clinical event flags.

Results

We included 1158 SLE patients (37% biopsy-confirmed LN) with 36 733 eGFR measures over a median of 7.6 years (IQR: 3.9–15.3). LN was associated with lower within-person mean eGFR [LN: 93.8 (s.d. 26.4) vs non-LN: 101.6 (s.d. 17.7) mL/min per 1.73 m2; P < 0.0001] and higher variance [LN median: 157.0 (IQR: 89.5, 268.9) vs non-LN median: 84.9 (IQR: 46.9, 138.2) (mL/min per 1.73 m2)2; P < 0.0001]. Increasing SLE-PRSs were associated with lower mean eGFR and greater variance, while increasing eGFR-PRS was associated with increased eGFR mean and variance.

Conclusion

We observed significant associations between SLE and eGFR PRSs and repeated eGFR measurements, in a large cohort of children and adults with SLE. Longitudinal eGFR may serve as a powerful alternative outcome to LN categories for discovery of LN risk loci.
UK experience of professional registration in radiation protection
Authors: Chapple Claire-Louise , Marsden Peter J , Rankine Alex
Published: March 2023

The UK Radiation Protection Council (RPC) was established in 2019, under the Royal Charter of the Society for Radiological Protection. The RPC holds the registers for three grades of professional registration—Chartered, Incorporated and Technical Radiation Protection Professional. Individual radiation protection practitioners may apply for registration through any society or organisation that has been accepted as a Licensee of the RPC. This paper will give an overview of the criteria used for registration at each level, along with the benefits of professional registration to individuals, employers, the radiation protection profession and the public. We will discuss the operation of the RPC and share the experience of its establishment, identifying key issues and potential pitfalls for other Societies wishing to go down this route. Future expectations for professional registration will be considered.
The Difficulties of Grandiose Delusions: Harms, Challenges, and Implications for Treatment Engagement
Authors: Isham Louise , Loe Bao Sheng , Hicks Alice , Wilson Natalie , Bentall Richard P , Freeman Daniel
Published: March 2023

Background and Hypothesis

Grandiose delusions may entail difficult responsibilities and detrimental actions for patients. Recognition of these consequences by patients may provide an avenue for engagement in treatment. Furthermore, when patients carry out actions within the delusional system (“immersion behaviors”) or spend considerable time thinking about their grandiose beliefs this may contribute to the persistence of the grandiosity and further harmful consequences. We, therefore, investigated grandiose-related subjective harm, immersion behaviors, and perseverative thinking.

Study Design

A cross-sectional study with 798 patients with psychosis (375 of whom had grandiose delusions) and 4518 nonclinical adults. Factor analyses using data from participants scoring highly on grandiosity were used to form 3 scales: subjective harm from exceptional experiences questionnaire; immersion behaviors questionnaire; and thinking about exceptional experiences questionnaire. Associations with grandiosity were tested using structural equation modeling.

Study Results

A total of 268 (77.9%) patients with grandiose delusions identified grandiose-related harms in the past 6 months and 199 (55.1%) wanted help. Immersion behaviors and perseverative thinking were highly prevalent, and explained 39.5% and 20.4% of the variance in grandiosity, respectively. Immersion behaviors and perseverative thinking were significantly associated with subjective harm, even when severity of grandiosity was controlled. Requests for help were associated with higher levels of subjective harm, use of immersion behaviors, and perseverative thinking but not severity of grandiosity.

Conclusions

Acting on grandiose delusions, including harmful behaviors and excessive thinking about grandiose delusions, may be routes for clinicians to engage patients in treatment. This could be a starting point for targeted psychological interventions for grandiose delusions.
Boundary work in the regional innovation policy mix: SME digital technology diffusion policies in Wales
Authors: Henderson Dylan
Published: March 2023

In recent decades, research has begun to examine the concept of the regional policy mix and its implications for regional innovation. While this has highlighted the role of interactions between multilevel policy instruments and the potential for duplication and synergies, it has tended to underplay the contribution of policy actors to managing such policy mix processes. This paper seeks to add to this literature by introducing the concept of boundary work, viewing it as a form of agency practice seeking to create, maintain, and disrupt instruments within the policy mix. Through a case study of digital technology diffusion instruments in Wales (UK), this paper examines the actors, practices, and effects of boundary work in the regional policy mix. The findings show that boundary work can help manage tensions in the policy mix through anticipatory practices but that complexity and uncertainty in the regional innovation policy mix present ongoing challenges to policymakers.
Natural selection differences detected in key protein domains between non-pathogenic and pathogenic feline coronavirus phenotypes
Authors: Zehr Jordan D , Kosakovsky Pond Sergei L , Millet Jean K , Olarte-Castillo Ximena A , Lucaci Alexander G , Shank Stephen D , Ceres Kristina M , Choi Annette , Whittaker Gary R , Goodman Laura B , Stanhope Michael J
Published: March 2023

Feline coronaviruses (FCoVs) commonly cause mild enteric infections in felines worldwide (termed feline enteric coronavirus [FECV]), with around 12 per cent developing into deadly feline infectious peritonitis (FIP; feline infectious peritonitis virus [FIPV]). Genomic differences between FECV and FIPV have been reported, yet the putative genotypic basis of the highly pathogenic phenotype remains unclear. Here, we used state-of-the-art molecular evolutionary genetic statistical techniques to identify and compare differences in natural selection pressure between FECV and FIPV sequences, as well as to identify FIPV- and FECV-specific signals of positive selection. We analyzed full-length FCoV protein coding genes thought to contain mutations associated with FIPV (Spike, ORF3abc, and ORF7ab). We identified two sites exhibiting differences in natural selection pressure between FECV and FIPV: one within the S1/S2 furin cleavage site (FCS) and the other within the fusion domain of Spike. We also found fifteen sites subject to positive selection associated with FIPV within Spike, eleven of which have not previously been suggested as possibly relevant to FIP development. These sites fall within Spike protein subdomains that participate in host cell receptor interaction, immune evasion, tropism shifts, host cellular entry, and viral escape. There were fourteen sites (twelve novel sites) within Spike under positive selection associated with the FECV phenotype, almost exclusively within the S1/S2 FCS and adjacent to C domain, along with a signal of relaxed selection in FIPV relative to FECV, suggesting that furin cleavage functionality may not be needed for FIPV. Positive selection inferred in ORF7b was associated with the FECV phenotype and included twenty-four positively selected sites, while ORF7b had signals of relaxed selection in FIPV. We found evidence of positive selection in ORF3c in FCoV-wide analyses, but no specific association with the FIPV or FECV phenotype. We hypothesize that some combination of mutations in FECV may contribute to FIP development, and that it is unlikely to be one singular ‘switch’ mutational event. This work expands our understanding of the complexities of FIP development and provides insights into how evolutionary forces may alter pathogenesis in coronavirus genomes.
Molecular phylogeny and taxonomy of three anaerobic plagiopyleans (Alveolata: Ciliophora), retrieved from two geographically distant localities in Asia and North America
Authors: Li Ran , Zhuang Wenbao , Feng Xiaochen , Al-Farraj Saleh A , Schrecengost Anna , Rotterova Johana , Beinart Roxanne A , Hu Xiaozhong
Published: March 2023

Anaerobic ciliates are key organisms for studying adaptations to an anaerobic lifestyle, the evolution of eukaryotic cell organelles, mechanisms of energy metabolism, and symbiosis with prokaryotes; however, the biodiversity of their marine representatives remains poorly known. In this study, three species of ciliates belonging to the class Plagiopylea, i.e. Trimyema foissnerisp. nov.,Plagiopyla rarisetasp. nov., and Plagiopyla frontata, collected from various marine anoxic habitats from two geographically distant continents, Asia and North America, were investigated using morphological and molecular methods. Trimyema foissneri can be recognized by three complete somatic ciliary girdles, special arrangement of kinetosomes near the anterior end of the oral kineties, and the presence of a ventrolateral fragment. Plagiopyla rariseta is distinguished by sparse cilia on the frontal region and particular orientation of the buccal cavity. Plagiopyla frontata is newly recorded and is redescribed in detail and redefined based on new populations. Phylogenetic analyses based on the small subunit ribosomal ribonucleic acid (SSU rRNA) gene supported the generic assignment of the three species and corroborated the monophyly of the families Trimyemidae and Plagiopylidae. An improved key to the identification of the valid species of genus Trimyema is also supplied.
Development of Glycine max Germplasm Highly Resistant to Sclerotinia sclerotiorum
Authors: Webster Richard W. , McCaghey Megan , Mueller Brian D. , Groves Carol L. , Mathew Febina M. , Singh Asheesh K. , Kabbage Mehdi , Smith Damon L.
Published: March 2023

Sclerotinia stem rot (SSR) of soybean caused by Sclerotinia sclerotiorum is a devastating disease of soybean, especially in the Upper Midwest region of the United States. To mitigate yield losses due to this disease, many control methods are available for producers, including cultural control practices, chemical control, and cultivars with quantitative resistance. However, due to there being few commercial cultivars with high levels of resistance, producers are often limited in their seed selection. The aim of this study was to develop novel conventional soybean cultivars with high levels of resistance to SSR, favorable agronomic traits, and resistance to additional economically important diseases. Initial crosses were conducted in 2016 with two different sources of SSR resistance. Across multiple generations of screening for resistance to SSR, three highly resistant soybean lines were identified as the elite lines. These elite lines were demonstrated to be highly resistant across multiple years in both greenhouse and field trials, including high levels of resistance to multiple diverse S. sclerotiorum isolates. The three selected elite lines also resulted in moderately high yields and favorable agronomic traits, such as low lodging and moderate branching, indicating their viability to be released for production. In addition to SSR resistance, these three elite lines demonstrated resistance to other economically important soybean diseases, such as frogeye leaf spot, anthracnose, Cercospora leaf blight, and brown stem rot. Overall, this work has led to three SSR-resistant soybean lines that could be useful for future breeding efforts or commercial soybean production.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The #ObGynInternChallenge: Reach, Adoption, Implementation, and Effectiveness of a Microlearning SMS-Distributed Curriculum
Authors: Cai Fei , Santiago Sarah , Southworth Elizabeth , Stephenson-Famy Alyssa , Fay Emily , Wang Eileen Y. , Burns R. Nicholas
Published: March 2023

Problem

While many medical schools have implemented bootcamps or specialized curricula to prepare medical students for residency, these programs are neither universal nor consistent in their content.

Approach

The authors created an electronic, multimodal, short messaging service (SMS)-distributed curriculum, called the #ObGynInternChallenge, to improve learners’ medical knowledge, based on the Council on Resident Education in Obstetrics and Gynecology educational objectives. The curriculum was open to all fourth-year medical students who matched into obstetrics and gynecology (Ob/Gyn). Daily messages were delivered to participants’ mobile devices via SMS for 25 consecutive weekdays, May 3–June 4, 2021. Each day’s message included an introduction with key facts, an infographic, a website link with a podcast and additional reference materials, and at least one question. The authors assessed its reach, adoption, implementation, and effectiveness.

Outcomes

For reach and adoption, total enrollment for the curriculum was 1,057 (72.0%) of 1,469 filled Ob/Gyn residency positions in the 2021 Match. The total cost of the intervention was $2,503.20 or $2.37 per participant. For implementation, all participants who signed up for the course received the daily messages, and 858/1,057 (81.2%) completed the course. Participants felt the curriculum was an excellent resource for studying (391/426, 91.8%) and the course was enjoyable to use (395/424, 93.2%). For effectiveness, mean score improvement was 11.6% (pre-test: 62.4%, post-test: 74.0%; P < .001). In the multivariate linear regression analysis, high podcast (P = .02) and website use (P = .002) were associated with greater score improvement. High social media use was associated with less improvement (P = .02).

Next Steps

This study suggests promise for a low-cost, largely satisfying SMS-distributed curriculum in terms of offering some benefit for short-term knowledge gain. Next steps include expanding such a curriculum to meet standard learning objectives for all fourth-year medical students entering residency.
The Relationship Between Chronic Pain, Depression, Psychosocial Factors, and Suicidality in Adolescents
Authors: Wildeboer Emily M. , Chambers Christine T. , Soltani Sabine , Noel Melanie
Published: March 2023

Background:

Chronic pain in youth is often associated with social conflict, depression, and suicidality. The interpersonal theory of suicide posits that there are psychosocial factors, such as peer victimization and lack of fear of pain, that may also influence suicidality.

Objectives:

The objective of this study was to determine whether depressive symptoms, peer victimization, and lack of fear of pain predict suicidality in adolescents with chronic pain. It was hypothesized that higher levels of depressive symptoms and peer victimization, and lower levels of fear of pain, would predict a higher lifetime prevalence of suicidality.

Methods:

Participants consisted of 184 youth with primary chronic pain conditions (10 to 18 y,M= 14.27 y). Measures included diagnostic clinical interviews assessing suicidality and self-report questionnaires assessing depressive symptoms, peer victimization, and fear of pain.

Results:

Forty-two (22.8%) participants reported suicidality. Regression analyses demonstrated that the occurrence of suicidality was associated with higher rates of depressive symptoms (β = 1.03,P= 0.020, 95% CI: 1.01, 1.06) and peer victimization (β = 2.23,P< 0.05, 95% CI: 1.07, 4.63), though there was no association between lower fear of pain and suicidality.

Discussion:

These results suggest that depressive symptoms and peer victimization are significant predictors of suicidality in adolescents with chronic pain; however, lower fear of pain was not shown to be a significant predictor. Given these findings, depression and peer victimization should be further explored and considered in the design and implementation of prevention and early intervention strategies that target chronic pain and suicidality in youth.
SRS-22r Self-Image After Surgery for Adolescent Idiopathic Scoliosis at 10-year Follow-up
Authors: Stone Lauren E. , Upasani Vidyadhar V. , Pahys Joshua M. , Fletcher Nicholas D. , George Stephen G. , Shah Suken A. , Bastrom Tracey P. , Bartley Carrie E. , Lenke Lawrence G. , Newton Peter O. , Kelly Michael P. ,   Harms Study Group
Published: March 2023

Study Design.

Retrospective cohort

Objective.

To examine SRS-Self Image scores at up to 10 years after surgery for adolescent idiopathic scoliosis (AIS).

Summary of Background Data.

Self-image is complex with implications for surgical and patient-reported outcomes after AIS surgery. Surgically modifiable factors that impact self-image are inconsistently reported in the literature with few longer-term reports. We examined the rate and durability of self-image improvement.

Materials and Methods.

An AIS registry was queried for patients with up to 10 years of follow-up after AIS surgery. A mixed effects model estimated change in SRS-22 Self Image from baseline to 6 weeks, 1 year, 2 years, 5 years, and 10 years. All enrolled patients contributed data to the mixed effects models. A sub-analysis of patients with 1-year and 10-year follow-up evaluated worsening/static/improved SRS-22 Self Image scores examined stability of scores over that timeline. Baseline demographic data and 1-year deformity magnitude data were compared between groups using parametric and nonparametric tests as appropriate.

Results.

Data from 4608 patients contributed data to the longitudinal model; 162 had 1-year and 10-year data. Mean SRS-Self Image improvement at 10-year follow-up was 1.0 (95% CI: 0.9–1.1) point. No significant changes in Self-Image domain scores were estimated from 1-year to 10-year (allP>0.05) postoperative. Forty (25%) patients had SRS-Self Image worsening from 1 year to 10 years, 36 (22%) improved, and 86 (53%) were unchanged. Patients who worsened over 10 years had lower SRS-Self Image at baseline than those unchanged at enrollment (3.3vs.3.7,P=0.007). Neither radiographic parameters nor SRS-Mental Health were different at baseline for the enrolled patients.

Conclusion.

Ten years after surgery, 75% of patients reported similar or better SRS-Self Image scores than one year after surgery. Nearly 25% of patients reported worsening self-image at 10 years. Patients who worsened had lower baseline SRS-Self Image scores, without radiographic or mental health differences at baseline or follow-up.
Risk Factors for Ambulatory Surgery Conversion to Extended Stay Among Patients Undergoing One-level or Two-level Posterior Lumbar Decompression
Authors: Dodo Yusuke , Okano Ichiro , Kelly Neil A. , Sanchez Leonardo A. , Haffer Henryk , Muellner Maximilian , Chiapparelli Erika , Oezel Lisa , Shue Jennifer , Lebl Darren R. , Cammisa Frank P. , Girardi Federico P. , Hughes Alexander P. , Sokunbi Gbolabo , Sama Andrew A.
Published: March 2023

Study design:

A retrospective observational study.

Objective.

The objective of this study was to investigate the factors associated with the conversion of patient status from ambulatory surgery (AMS) to observation service (OS) (<48 h) or inpatient (>48 h).

Summary of Background Data.

AMS is becoming increasingly common in the United States because it is associated with a similar quality of care compared with inpatient surgery, significant costs reduction, and patients’ desire to recuperate at home. However, there are instances when AMS patients may be subjected to extended hospital stays. Unanticipated extension of hospitalization stays can be a great burden not only to patients but to medical providers and insurance companies alike.

Materials and Methods.

Data from 1096 patients who underwent one-level or two-level lumbar decompression AMS at an in-hospital, outpatient surgical facility between January 1, 2019, and March 16, 2020, were collected. Patients were categorized into three groups based on length of stay: (1) AMS, (2) OS, or (3) inpatient. Demographics, comorbidities, surgical information, and administrative information were collected. Simple and multivariable logistic regression analyses were conducted comparing AMS patients and OS/inpatient as well as OS and inpatients.

Results.

Of the 1096 patients, 641 (58%) patients were converted to either OS (n=486) or inpatient (n=155). The multivariable analysis demonstrated that age (more than 80 yr old), high American Society of Anesthesiologists Physical Status (ASA) grade, history of sleep apnea, drain use, high estimated blood loss, long operation, late operation start time, and a high pain score were considered independent risk factors for AMS conversion to OS/inpatient. The risk factors for OS conversion to inpatient were an ASA class 3 or higher, coronary artery disease, diabetes mellitus, hypothyroidism, steroid use, drain use, dural tear, and laminectomy.

Conclusions.

Several surgical factors along with patient-specific factors were significantly associated with AMS conversion. Addressing modifiable surgical factors might reduce the AMS conversion rate and be beneficial to patients and facilities.
Telomerase-mediated immortalization of human vaginal wall fibroblasts derived from patients with pelvic organ prolapse
Authors: Guo Tao , Xie Ting , Lang Jinghe , Sun Zhijing
Published: March 2023

Background:

Extracellular matrix (ECM) remodeling is the most important pathomechanism of pelvic organ prolapse (POP). Fibroblasts are the key to ECM regulation. The passaging capacity of human vaginal wall fibroblasts (hVWFs) is limited in vitro. Here, we aimed to immortalize hVWFs through the introduction of human telomerase reverse transcriptase (hTERT).

Methods:

Primary cells were derived from the vaginal wall tissue of patients with POP. Cellular senescence was detected via senescence-associated β-galactosidase staining. We employed a lentiviral transfection vector to stably express hTERT in hVWFs at passage 3, generating immortalized hVWFs (i-hVWFs). We then assessed cellular proliferation via the CCK-8 and EdU assays as well as cellular migration via wound healing assays. G-banded chromosome karyotypic analysis was performed to evaluate chromosomal karyotype stability. Finally, cellular tumorigenesis capacity was assessed in nude mice. A two-tailed Student's t test was used to compare differences between the two groups.

Results:

Our results showed that senescence of primary hVWFs significantly increased from passage seven. From passage 11, hVWFs showed a significantly higher senescence percentage than i-hVWFs. During the continuous passage, i-hVWFs presented stability in proliferation, migration capacity, expression of ECM regulation-related genes, and chromosome karyotype. In vivo tumorigenesis was absent in i-hVWFs.

Conclusions:

The senescence of hVWFs significantly increased from the seventh passage, and we successfully used hTERT to immortalize hVWFs derived from patients with POP. Studies on POP that require a long-lived hVWF line will benefit from our technique.
Nonalcoholic Fatty Liver Disease as an Emerging Risk Factor and Potential Intervention Target for Atherosclerotic Cardiovascular Diseases
Authors: Zhang Daqing , Mi Zhen , Peng Jiya , Yang Tiangui , Han Yuze , Zhai Yujia , Song Chenliang , Teng Xianzhuo , Sun Wei , Guo Jing , Bilonda Kabeya Paulin
Published: March 2023

Nonalcoholic fatty liver disease (NAFLD) is an underappreciated independent risk factor for atherosclerotic cardiovascular diseases (ASCVDs). In recent years, the risk of ASCVD has increased along with the prevalence of NAFLD. ASCVD events are highly prevalent and are the main contributor to death in patients with NAFLD. The association between NAFLD and ASCVD has been validated in numerous observational, cohort, and genetic studies. Most of these studies agree that NAFLD significantly increases the risk of developing atherosclerosis and ASCVD. In addition, the underlying proatherosclerotic mechanisms of NAFLD have been gradually revealed; both disorders share several common pathophysiologic mechanisms including insulin resistance, whereas systemic inflammation and dyslipidemia driven by NAFLD directly promote atherosclerosis. Recently, NAFLD, as an emerging risk enhancer for ASCVD, has attracted attention as a potential treatment target for ASCVD. This brief review aims to illustrate the potential mechanistic insights, present recent clinically relevant investigations, and further explore the emerging therapies such as novel antidiabetic and lipid-lowering agents that could improve NAFLD and reduce ASCVD risk.
Role of Cisplatin Dose Intensity and TPMT Variation in the Development of Hearing Loss in Children
Authors: Siemens Angela , Brooks Beth , Rassekh S. Rod , Meijer Annelot J.M. , van den Heuvel-Eibrink Mary M. , Xu Wei , Loucks Catrina M. , Ross Colin J.D. , Carleton Bruce C. ,   on behalf of the Canadian Pharmacogenomics Network for Drug Safety Consortium
Published: March 2023

Background:

Cisplatin, widely used in the treatment of solid tumors, causes permanent hearing loss in more than 60% of treated children. Previous studies have implicated several clinical factors in the development of ototoxicity, including cumulative cisplatin dose. However, the role of cisplatin dose intensity in the development of hearing loss in children remains unclear. Pharmacogenetic studies have also identified genetic variants in TPMT that increase the risk of cisplatin-induced hearing loss. This study aims to determine whether cisplatin dose intensity contributes to the risk of hearing loss in children and whether genetic variations in TPMT further modifies the risk of cisplatin-induced hearing loss.

Methods:

The authors genotyped 371 cisplatin-treated children for the presence of any 3 TPMT-risk variants. Patients were categorized into high-, moderate-, and low-intensity cisplatin dosing groups according to the cisplatin dose administered per unit time. Kaplan–Meier curves were plotted to compare the cumulative incidence of hearing loss between the genotype and dose intensity groups.

Results:

Patients receiving cisplatin at high dose intensity experienced significantly higher incidences of ototoxicity than those receiving cisplatin at low dose intensity (P = 9 × 10−7). Further stratification by TPMT genotype revealed that carriers of ≥1 TPMT variants receiving high-intensity cisplatin developed ototoxicity sooner and more often than their wild-type counterparts (93.8% vs. 56.6% at 12 months; P = 5 × 10−5) and noncarriers receiving low-intensity cisplatin (21.2% at 12 months).

Conclusions:

Cisplatin dose intensity is strongly associated with ototoxicity development in children, and this risk is further increased by the presence of TPMT-risk alleles.
Usefulness of Therapeutic Drug Monitoring and Pharmacogenetics for a Patient Treated with Olanzapine, Buspirone, and Fluvoxamine: A Case Study
Authors: Ding Jing , Yang Liu , Zhang Yan , Meng Zhuocheng , Ren Jianli , Zhang Suo , Liu Jiarui , Cui Xiaohua
Published: March 2023

Background:

A patient, with a mental disorder caused by an intracranial infection, treated with olanzapine, fluvoxamine, and buspirone. The plasma exposure of olanzapine was too high at standard doses, with evidence indicating that it was caused by drug–drug interactions.

Methods:

Using pharmacogenomics and therapeutic drug monitoring to guide drug dose adjustment for a patient in clinical practice.

Results:

The patient underwent pharmacogenetic testing in addition to therapeutic drug monitoring as part of a pharmacist-led comprehensive evaluation of medication therapy management in a clinical setting, resulting in improved clinical efficacy that allowed discharge from a psychiatric hospital.

Conclusions:

This case study demonstrates that therapeutic drug monitoring combined with pharmacogenetic-guided dose adjustment can aid in the management of patients receiving complex pharmacological treatments.
Prophylactic salpingectomy with delayed oophorectomy as a two-staged alternative for primary prevention of ovarian cancer in BRCA1/2 mutation carriers: women's point of view
Authors: Mohr-Sasson Aya , Dadon Tal , Perri Tamar , Rosenblat Orgad , Friedman Eitan , Korach Jacob
Published: March 2023

Objective

This study aimed to determine BRCA-mutation carrier women's interest and acceptability of participating in a study examining prophylactic salpingectomy with delayed oophorectomy (PSDO) as an alternative to the current recommendation for bilateral salpingo-oophorectomy for risk reduction.

Methods

This is a cross-sectional questionnaire-based study. All women visiting the high-risk clinics for hereditary breast and ovarian cancer in a single tertiary medical center were asked to complete a questionnaire concerning the two-stage approach from October 2018 to December 2019. Before completing the questionnaire, detailed explanation was given by a senior physician regarding the procedure, related background, possible risks, and benefits.

Results

The study population included 293 women, of whom 183 (62.4%) were BRCA1 mutation carriers, 97 (33.1%) were BRCA2 mutation carriers, and 13 (4.4%) had unknown familial mutation. Risk-reducing surgery was completed in 160 (55.17%) of the women. First-degree and second-degree family history was reported in 166 (57.24%) and 52 (17.9%) of the women, respectively. Among women surveyed, more than half of the women (n = 66 [51%]) who had yet to undergo risk-reducing surgery reported interest in having PSDO. Similarly, among those who had already received prophylactic surgery, 64 (40%) also considered PSDO to be an acceptable alternative. Multivariate logistic regression analysis found family history of related malignancies to be the only independent factor associated with reduced interest in a study of PSDO (odds ratio, 0.15 [95% confidence interval, 0.29-0.77]; P = 0.02).

Conclusions

Overall, BRCA-mutation carrier women indicated interest in PSDO risk-reducing surgery, taking into consideration the potential additional risk. These findings suggest that a clinical study exploring the equivalence of PSDO as alternative treatment is feasible.
Development and psychometric properties of a measurement to ascertain the impact of genitourinary symptoms on health-related quality of life in menopausal women: the Cervantes-GSM questionnaire
Authors: Baquedano Laura , Rejas-Gutiérrez Javier , Coronado Pluvio J.
Published: March 2023

Objective

The Cervantes-GSM questionnaire is a novel tool currently being developed to examine the impact of genitourinary symptoms on health-related quality of life in adult women with genitourinary syndrome of menopause (GSM).

Methods

A literature review and cognitive debriefing were conducted in women with GSM, which provided the basis for creating a draft questionnaire. This draft version was pilot-tested to check participant comprehension and ease of completion. The initial draft was then refined to obtain a 15-item version with five domains whose initial psychometric properties were analyzed in 130 adult women with GSM. The psychometric properties tested in this study were factorial structure, feasibility, reliability, and construct validity.

Results

The Cervantes-GSM 15-item questionnaire consists of five domains: vulvovaginal symptoms, urinary symptoms, psychological (emotions), interference with daily activities, and sexuality. The instrument was shown to be feasible and easy to complete, regardless of age or educational level. Internal consistency was high (Cronbach α = 0.88). Construct validity was supported by convergent-divergent validity showing higher correlation coefficients between items in their own domain (>0.70) than with the other items and domains in the questionnaire. Cervantes-GSM also showed known group validity with significant differences in total score and most domains (13-20 points, P < 0.01) regardless of whether women chose local treatment of their genitourinary symptoms.

Conclusion

This study presents a novel questionnaire capable of assessing health-related quality of life in menopausal women with GSM. The tool has shown acceptable preliminary psychometric properties, including feasibility, factor structure, construct validity, and internal consistency.
Clinical and Laboratory Characteristics of Hemophagocytic Lymphohistiocytosis in Children With Severe Dengue During the 2019–2020 Outbreak in Southern Colombia
Authors: Restrepo Arias Valeria Camila , Salgado García Doris M. , Merchán-Galvis Angela M. , Narváez Carlos F.
Published: March 2023

Background:

Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled activation of inflammatory cells and an exaggerated release of cytokines. It can be triggered by different factors, including viruses, such as dengue. The objective of this study was to characterize the clinical and laboratory profiles of children with severe dengue and HLH, and to identify the risk factors for this clinical complication.

Methods:

An analytical study was conducted in children with severe dengue who were treated in an intensive care unit between January 2019 and March 2020. Clinical and laboratory factors were compared between patients with and without HLH.

Results:

HLH represented 13.4% (15/112) of children with severe dengue. Patients with HLH had a long-lasting fever (10.1 vs. 5.8 days; P = 0.012), low hemoglobin levels (7.6 vs. 10.8 g/dL; P = 0.000) and high aspartate aminotransferase values (4443 vs. 1061 U/L; P = 0.002), alanine transaminase (1433 vs. 487 U/L; P = 0.004), partial thromboplastin time (80.6 vs. 51.8 seconds; P = 0.010), prothrombin time (23.5 vs. 19.6 seconds; P = 0.024), triglycerides (333.7 vs. 223.2 mg/dL; P = 0.005), lactate dehydrogenase (4209 vs. 1947 U/L; P = 0.006), soluble CD25 (3488 vs. 1026 pg/mL; P = 0.014), and presented with higher frequency of myocarditis (66.7% vs. 38.3%; P = 0.048), hepatitis (5.3% vs. 1.3%; P = 0.014), bacterial coinfection (73.3% vs. 26.7%; P = 0.010) and fatal outcome (26% vs. 5%; P = 0.037).

Conclusions:

HLH is a serious life-threatening clinical complication of dengue virus infection that must be considered, particularly during outbreaks.
Expanding the Differential for Alternative Diagnoses in the Workup of Multisystem Inflammatory Syndrome in Children
Authors: Kaneta Kelli , Malhotra Sanchi , Szmuszkovicz Jacqueline , Mohandas Sindhu , White Sarah , Wu Susan
Published: March 2023

Background:

Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome associated with SARS-CoV-2 infection. Children are increasingly admitted for MIS-C evaluation, but instead found to have alternative diagnoses.

Methods:

Retrospective study of all pediatric patients <21 years of age hospitalized between August 1, 2020, and July 31, 2021, with clinical concern for MIS-C at the time of presentation were identified through use of an institutional computerized MIS-C order entry set. Final diagnoses were then collected through primary review of the medical record from the time of initial presentation through 1-month postdischarge.

Results:

Of 359 cases identified through the MIS-C order entry set, 126 (35.1%) met criteria for MIS-C, 28 had Kawasaki Disease (KD) (7.8%), and 11 cases met criteria for both MIS-C and KD (3.1%), leaving 194 (54.0%) patients ruled out and categorized as “MIS-C mimickers.” Infectious diagnoses were the most common MIS-C mimickers (78.9%). Of the infectious etiologies, bacterial (51.0%) and viral (52.3%) etiologies were seen with similar frequency.

Conclusions:

We describe MIS-C mimickers spanning multiple subspecialties, with infectious etiologies predominating, which can aid clinicians in the consideration of diagnostic testing, with the goal of achieving timely and accurate diagnoses.
Worldwide Prevalence of Carbapenem Resistance in Acinetobacter baumannii
Authors: Tavasol Arian , Khademolhosseini Sara , Noormohamad Mehdi , Ghasemi Maryam , Mahram Hadis , Salimi Maryam , Fathi Mobina , Sardaripour Alireza , Zangi Masood
Published: March 2023

Introduction

Acinetobacter baumanniiis an opportunistic pathogen that can cause hospital-acquired infections. Indiscriminate use of antibiotics has led to a significant increase in the incidence of acquired drug resistance among clinical isolates ofA. baumannii. This study aims to assess the resistance to carbapenems betweenA. baumanniiclinical isolates using a meta-analysis study.

Methods

The databases of Scopus, PubMed, Google Scholar, Web of Science, and Iranian national databases (SID, Magiran, and IranMedex) were searched until 2020. Studies were analyzed based on the random-effects model. Heterogeneity between studies was evaluated by calculating theI2index. Statistical analysis was performed using STATA (version 14.2; StataCorp, College Station, Tex).

Results

Finally, 46 articles were found to meet the criteria, with a total sample size of 62,779 cases. Resistance to imipenem and meropenem was detected in 62% and 64% of cases, respectively. The sensitivity ofA. baumanniiclinical isolates to imipenem and meropenem was obtained at 34% and 37%, respectively. In addition, the highest resistance to imipenem and meropenem was estimated in Asia (67% and 70%, respectively). However, the lowest resistance to imipenem and meropenem was estimated in Europe (50% and 57%, respectively).

Conclusion

The carbapenem resistance ofA. baumanniiis a global health problem that affects public health in the community. Based on our results, because of the high resistance ofA. baumanniito carbapenems, the extensive use of carbapenems is less recommended.
Drug treatment of COVID-19 infection
Authors: Lui Grace , Guaraldi Giovanni
Published: March 2023

Purpose of review

COVID-19 pandemic has caused more than 6.6 million deaths globally. Tremendous efforts have been committed for the development of new and repurposed drugs for the treatment of COVID-19. Although different international and national guidelines share consensus in the management of COVID-19 disease with different levels of severity, new challenges have emerged, steering the need for ongoing research in advancing the clinical management of COVID-19.

Recent findings

This review focuses on recent data from randomized trials and postmarketing real-world evidence for the treatment of mild to moderate disease in the outpatient setting and patients hospitalized for COVID-19 with varying level of severity. Relevant data for treatment of the latest omicron sub-variants in people who received vaccination are presented. Challenges in special populations, including immunocompromised hosts, patients with renal failure and pregnant women, are also discussed.

Treatment of COVID-19 should be personalized according to host characteristics, degree of severity and available treatment options.
Gram-negative pulmonary infections – advances in epidemiology and diagnosis
Authors: Radulescu Mihaela , Gant Vanya
Published: March 2023

Purpose of review

Pulmonary infections due to Gram-negative organisms are increasing worldwide and traditional assumptions that these are limited to hospital and ventilator-acquired pneumonia are rapidly falling away. Accordingly, empiric antibiotic guidelines have to follow suit with ever broader spectrum choices in order to remain ‘safe’, as the Global prevalence of extensively resistant Gram-negative organisms inexorably increases. Rapid, multiplex PCR-based detection of a wide variety of potential pathogens offers the opportunity to replace empiric antibiotic choices with targeted, evidence-based therapy in clinically actionable timeframes.

Recent findings

Here, we describe the data underpinning both the increasing global prevalence of Gram-negative pulmonary infections and their increasing antibiotic resistance. We also describe the performance, characteristics and early emerging clinical impact of already available rapid molecular diagnostic platforms and how they might best be deployed.

It will likely be advantageous to replace the current trend for empiric prescription of increasingly broad-spectrum antibiotics with ‘same day’ evidence-based, targeted therapy using high performance, rapid molecular diagnostic solutions. Several challenges remain be overcome, however, to fully realize their clear potential for better, focussed deployment of antibiotics, improved patient outcomes and antibiotic stewardship.
Assessment of Patients With ARFID Presenting to Multi-Disciplinary Tertiary Care Program
Authors: Richmond Tracy K. , Carmody Julia , Freizinger Melissa , Milliren Carly E. , Crowley P. McGreggor , Jhe Grace B. , Bern Elana
Published: March 2023

There are no standard assessment approaches for Avoidant Restrictive Food Intake Disorder (ARFID). We describe our approach to multidisciplinary assessment after assessing more than 550 patients with ARFID. We collected online survey (ARFID-specific instruments, measures of anxiety, depression) measures. Electronic medical record data (mental health and gastrointestinal diagnoses, micronutrient and bone density assessments, and growth parameters) were extracted for the 239 patients with ARFID seen between 2018 and 2021 with both parent and patient responses to online surveys. We identified 5 subtypes/combinations of subtypes: low appetite; sensory sensitivity; fear + sensory sensitivity; fear + low appetite; fear + sensory sensitivity + low appetite. Those with appetite-only subtype had higher mean age (14.0 years, P < 0.01) and the lowest average body mass index z score (–1.74, P < 0.01) compared to other subtypes. Our experience adds to understanding of clinical presentations in patients with ARFID and may aid in assessment formulation.
Compassion Fatigue and Ethical Attitudes in Nursing Care in Intensive Care Nurses During the COVID-19 Pandemic
Authors: Gurdap Zuleyha , Cengiz Zeliha
Published: March 2023

Background:

Intensive care unit (ICU) nurses faced an increased risk of compassion fatigue and ethical concerns during the COVID-19 pandemic.

Purpose:

To evaluate compassion fatigue of ICU nurses and their ethical attitudes in care during the COVID-19 pandemic and analyze contributing factors.

Methods:

An exploratory cross-sectional research design was used.

Results:

A total of 103 ICU nurses participated. The nurses' compassion fatigue and ethical attitude scores were high. Compassion fatigue was explained by the following variables: considering resigning, receiving support for ethical decisions, willingness to work in the ICU, duration of providing activities of daily living in a shift, and number of patients per nurse.

Conclusions:

Compassion fatigue was high in nurses working in the ICU during COVID-19. The high level of ethical attitudes shows commitment to professional ethics and reflects the development of the nurses' professional identity. Implementation of interventions that help improve compassion fatigue among nurses is needed.
Establishing a Pathway to Excellence® Research Agenda
Authors: Mulvey Tanya , Cámpoli Marcela , Lundmark Vicki
Published: March 2023

OBJECTIVE

The aim of this study was to develop research priorities for positive practice environments identified by Pathway to Excellence® (Pathway) leaders and appraisers.

BACKGROUND

Identifying research priorities achieves 2 goals: 1) advancing research agendas that impact improving practice environments, and nurse and patient outcomes; and 2) informing nursing leaders, researchers, and funders of potential research projects to conduct and support.

METHODS

Research topics related to the 6 Pathway standards were developed and then rated for importance through 3 rounds of a Delphi survey by leaders at Pathway-designated organizations and Pathway appraisers.

RESULTS

Twenty research priorities were identified from the initial 54 research topics. The top 2 priorities were building and maintaining shared governance participation (91.9%) and nurse participation in performance improvement and evidence-based practice activities (90.7%).

CONCLUSIONS

Establishing a Pathway research agenda will guide nursing leadership, researchers, and funders in selecting impactful research priorities to help bolster positive practice environments that engage and empower nurses.
Components of Professional Practice Models
Authors: Wolf Zane Robinson , Cara Chantal , Bernard Noreen , Turkel Marian , Drenkard Karen
Published: March 2023

OBJECTIVE

This study describes common components of nursing professional practice models (NPPMs) of Magnet®-designated nursing service organizations.

BACKGROUND

Components of professional practice models have not been consistently analyzed, suggesting a need to identify their concepts. Evidence-based guidelines may be unavailable to assist in the creation and revision of models.

METHODS

A checklist was used to analyze 56 Web-based NPPMs of Magnet-designated nursing departments.

RESULTS

Checklist items showed a match with parent organizations, an emphasis on patient- or family-centered care, a commitment to quality nursing services, and nursing's professional distinctiveness. Responses indicated engagement in shared governance and support of nursing staff's professional development. The concepts of health, care of sick and well people, and scope of nursing services were inconsistently addressed and call for further research.

CONCLUSION

Nurse leaders should examine concepts in NPPMs and the extent they distinguish nursing's professional identity both within and externally to the organization.