bluuebunny/crossref_metadata_2025 huggingface dataset:
Five actions for five people: emergency cesarean section protocol
Authors: Mannella Paolo , Pancetti Federica , Giannini Andrea , Russo Eleonora , Montt-Guevara Magdalena , Simoncini Tommaso
Published: April 2023

Objective

The scope of this work is to evaluate an operative protocol for emergency C-section to improve teamwork and reduce surgical setup time.

Methods

Sixty-six health care operators working together in the delivery ward (gynecologists, midwives, anesthesiologists) simulated an emergency scenario applying a “five actions for each operator” protocol. For each simulation, the decision to delivery interval was considered and the perception of each operator as a team worker was analyzed with specific tests.

Results

The “five actions for five people” protocol significantly reduces the decision to delivery interval (p < 0.001) for emergency C-section. At the same time, a simple and codified scheme improves communication among team members, avoids overlapping roles. Indeed, all the operators become more aware of being helpful to the team (p < 0.001).

Conclusion

The use of a standardized, simple, and immediately usable protocol improves the performance of the delivery room team in terms of the urgency and quality of the operator’s participation in the event. Procedures of this type should be favored within emergency obstetric settings.

Trial registration number

CEAVNO 19-01-23. Local ethical Committee (COMITATO ETICO REGIONALE PER LA SPERIMENTAZIONE CLINICA - Sezione autonoma Area Vasta Nord Ovest -CEAVNO) approved this study as simulation training study. All the operators participated voluntary during their working time.
Highly sensitive droplet digital PCR for detection of RET fusion in papillary thyroid cancer
Authors: Chen Mengke , Xue Junyu , Sang Ye , Jiang Wenting , He Weiman , Hong Shubin , Lv Weiming , Xiao Haipeng , Liu Rengyun
Published: April 2023

Background

Thyroid cancer is the most frequent malignancy of the endocrine system, of which papillary thyroid cancer (PTC) is the predominant form with a rapid increasing incidence worldwide. Rearranged during transfection (RET) fusions are common genetic drivers of PTC and the potent RET inhibitor selpercatinib has been recently approved for treating advanced or metastatic RET fusion-positive thyroid cancer. In this study we aimed to develop a droplet digital PCR (ddPCR) system to accurately detect RET fusion in PTC samples.

Methods

The frequency and distribution of RET fusions in PTC were analyzed using genomic data of 402 PTC patients in The Cancer Genome Atlas (TCGA) database. To establish the ddPCR system for detecting CCDC6::RET fusion, a plasmid containing CCDC6::RET infusion fragment was constructed as standard template, the annealing temperature and concentrations of primers and probe were optimized. The analytical performance of ddPCR and quantitative reverse transcription PCR (qRT-PCR) were assessed in standard templates and tissue samples from 112 PTC patients. Sanger sequencing was performed in all the RET fusion-positive samples identified by ddPCR.

Results

RET fusions were observed in 25 (6.2%) of the 402 TCGA samples, and 15 (60%) of the RET fusion-positive patients had the CCDC6::RET fusion. Compared with qRT-PCR, the ddPCR method showed a lower limit of detection (128.0 and 430.7 copies/reaction for ddPCR and qRT-PCR, respectively). When applying the two methods to 112 tissue samples of PTC, eleven (9.8%) CCDC6::RET fusion-positive samples were detected by qRT-PCR, while ddPCR identified 4 additional positive samples (15/112, 13.4%). All the CCDC6::RET fusion-positive cases identified by ddPCR were confirmed by Sanger sequencing except for one case with 0.14 copies/uL of the fusion.

Conclusion

The accurate and sensitive ddPCR method reported here is powerful to detection CCDC6::RET fusion in PTC samples, application of this method would benefit more RET fusion-positive patients in the clinic.
Congenital peribronchial myofibroblastic tumor (CPMT): a case report with long term follow-up and next-generation sequencing (NGS)
Authors: Zhou Ping , Li Shuang , Wang Weiya , Tang Yuan , Jiang Lili
Published: April 2023

Background

Congenital peribronchial myofibroblastic tumor (CPMT) is an extremely rare lung disease in infants. It shows benign behavior and has a favorable survival after surgical treatment. CPMT was reported only in cases. Here, we report the longest follow-up known case of CPMT and review the clinical, radiographic and histopathological features of the published literature.

Case presentation

Ultrasound examination at 30 weeks of gestational age of a healthy 29-year-old female revealed a solid mass in the left lung. Computed tomography (CT) revealed a mass in the left lower lobe. The tumor was removed by lobectomy and pathologically diagnosed with CPMT. The tumor was composed of cartilage, spindle cells and oval cells. Vimentin was strongly positive. Smooth muscle actin (SMA) was positive in the spindle cells. The histopathologic and immunohistochemical features were similar to those in the literature. No ETV6-NTRK3 fusion or ALK rearrangement was detected. Gene mutations in JAK2 and SMO were detected by NGS. She is currently alive for 8 years with no evidence of disease recurrence.

Conclusions

CPMT is a rare lung tumor in infants. Surgical treatment is recommended for CPMT. The prognosis after successful surgery is favorable. The final diagnosis was histopathologic findings. Due to its cellularity, mitotic activity and rapid growth, long-term follow-up should be strengthened. The present patient is alive and well for 8 years after the surgery without recurrence. Gene mutations in JAK2 and SMO were detected, which may be associated with the formation of CPMT.
Prevalence of probable mental, neurological and substance use conditions and case detection at primary healthcare facilities across three districts in Ghana: findings from a cross-sectional health facility survey
Authors: Ae-Ngibise Kenneth Ayuurebobi , Sakyi Lionel , Adwan-Kamara Lyla , Lund Crick , Weobong Benedict
Published: April 2023

Background

Few studies have examined the prevalence of mental, neurological and substance use (MNS) conditions, case detection and treatment in primary healthcare in rural settings in Africa. We assessed prevalence and case detection at primary healthcare facilities in low-resource rural settings in Ghana.

Methods

A cross-sectional survey was conducted at the health facility level in three demonstration districts situated in Bongo (Upper East Region), Asunafo North (Ahafo Region) and Anloga (Volta Region) in Ghana. The study participants were resident adult (> 17 years) out-patients seeking healthcare at primary care facilities in each of the three demonstration districts. Data were collected on five priority MNS conditions: depression, psychosis, suicidal behaviour, epilepsy and alcohol use disorders.

Results

Nine hundred and nine (909) people participated in the survey. The prevalence of probable depression was 15.6% (142/909), probable psychotic symptoms was 12% (109/909), probable suicidal behaviour was 11.8% (107/909), probable epilepsy was 13.1% (119/909) and probable alcohol use disorders was 7.8% (71/909). The proportion of missed detection for cases of depression, self-reported psychotic symptoms, epilepsy and alcohol use disorders (AUD) ranged from 94.4 to 99.2%, and was similar across study districts. Depression was associated with self-reported psychotic symptoms (RR: 1.68; 95% CI: 1.12–1.54). For self-reported psychotic symptoms, a reduced risk was noted for being married (RR: 0.62; 95% CI: 0.39–0.98) and having a tertiary level education (RR: 0.12; 95% CI: 0.02–0.84). Increased risk of suicidal behaviour was observed for those attending a health facility in Asunafo (RR: 2.31; 95% CI: 1.27–4.19) and Anloga districts (RR: 3.32; 95% CI: 1.93–5.71). Age group of 35 to 44 years (RR: 0.43; 95% CI: 0.20–0.90) was associated with reduced risk of epilepsy. Being female (RR: 0.19; 95% CI: 0.12–0.31) and having a tertiary education (RR: 0.27; 95% CI: 0.08–0.92) were associated with reduced risk of AUD.

Conclusions

Our study found a relatively high prevalence of probable MNS conditions, and very low detection and treatment rates in rural primary care settings in Ghana. There is a need to improve the capacity of primary care health workers to detect and manage MNS conditions.
Association between mental disorders and adherence to antiretroviral treatment in health facilities in two Mozambican provinces in 2018: a cross-sectional study
Authors: Mandlate Flavio M. , Greene M. Claire , Pereira Luis F. , Gouveia Maria Lidia , Mari Jair Jesus , Cournos Francine , Duarte Cristiane S. , Oquendo Maria A. , Mello Marcelo Feijó , Wainberg Milton L.
Published: April 2023

Introduction

Lower adherence to antiretroviral treatment (ART) has been found among people with HIV (PWH) who have comorbid mental disorders like depression and alcohol use in Sub-Saharan African. However, there has been less exploration with regards to other mental disorders.

Methods

This study assessed the association of multiple mental disorders and adherence to ART based on the data from primary/tertiary health care facilities in Maputo and Nampula, Mozambique. We administered a sociodemographic questionnaire, Mini International Neuropsychiatric Interview (MINI) Plus 4.0.0 adapted for use in Mozambique to assess mental conditions, and a 3-item self-report to measure ART adherence.

Results

395 HIV-positive (self-report) participants on ART, with an average age of 36.7 years (SD = 9.8), and 30.4% were male. The most common mental disorders were major depressive disorder (27.34%) followed by psychosis (22.03%), suicidal ideation/behavior (15.44%), and alcohol-use disorder (8.35%). Higher odds of missing at least one dose in the last 30 days (OR = 1.45, 95% CI: 1.01, 2.10) were found in participants with any mental disorder compared to those without a mental disorder. The highest levels of non-adherence were observed among those with drug use disorders and panic disorder.

Conclusions

In Mozambique, PWH with any co-occurring mental conditions had a lower probability of ART adherence. Integrating comprehensive mental health assessment and treatment and ART adherence interventions tailored to PWH with co-occurring mental disorders is necessary to attain optimal ART adherence and reach the UNAIDS ART target.
Validity and reliability of the swedish versions of the HLS-EU-Q16 and HLS-EU-Q6 questionnaires
Authors: Bergman Lina , Nilsson Ulrica , Dahlberg Karuna , Jaensson Maria , Wångdahl Josefin
Published: April 2023

Background

Health Literacy is a crucial factor for health. In Europe, many people have limited health literacy (i.e. difficulties with accessing, understanding, appraising and using health information). This study aimed to evaluate the psychometrics of the Swedish versions of the HLS-EU-Q16 and HLS-EU-Q6, instruments that aims to assess health literacy.

Methods

In this prospective psychometric study convenience sampling was used, which gave a study population of 347 Swedish-speaking adults. The psychometric evaluation included item distributional statistics, construct validity testing, and principal component analysis to assess structural validity. Internal consistency and test-retest reliability was also investigated.

Results

For the Swedish version of HLS-EU-Q16, no floor effects were detected but a ceiling effect was noted among 28% of the respondents. Construct validity was supported as four out of five expected correlations was confirmed (educational level, self-perceived health, electronic health literacy and HLS-EU-Q6). In terms of structural validity, the principal component analysis yielded a four-factor structure with most items loading significantly only to one factor. The Swedish version of HLS-EU-Q16 had acceptable internal consistency (Cronbach’s α = 0.89, split-half reliability = 0.93) and test-retest reliability showed stability over time (Cohen’s κ = 0.822). For the Swedish version of HLS-EU-Q6, neither floor nor ceiling effects were observed. Construct validity was supported as HLS-EU-Q6 correlated as our a priori stated hypothesis. The principal component analysis did not support the unidimensionality of the scale as a two-factor structure was identified. The Swedish version of HLS-EU-Q6 had acceptable internal consistency (Cronbach’s α = 0.77, split-half reliability = 0.80) and test-retest reliability showed stability over time (Cohen’s κ = 0.812). According to the Swedish version of the HLS-EU-Q16, 71% of the participants were classified as having sufficient comprehensive health knowledge (CHL), while only 33% were classified as having this when the HLS-EU-Q6 was used.

Conclusions

The Swedish versions of the HLS-EU-Q16 and HLS-EU-Q6 have acceptable psychometric properties, and based on the results we recommend its use to measure CHL. However, we are hesitant to use Sw-HLS-EU-Q6 in estimating different CHL levels and further studies need to be conducted to establish validity and accuracy of the thresholds of HLS-EU-Q6.
Domestic violence assault during the first year of the COVID-19 pandemic: a longitudinal community study
Authors: Kofman Yasmin B. , Weiss Cassidy C. D. , Yim Ilona S.
Published: April 2023

Background

The consequences of the COVID-19 pandemic have been far-reaching, disproportionately impacting vulnerable populations. Of particular concern is the impact on individuals experiencing domestic violence (DV), an urgent public health issue. There have been numerous reports of pandemic-related surges in DV, and it has been speculated that prolonged periods of state-mandated isolation may be the source of these surges. The current study utilized publicly available records to examine fluctuations in DV coinciding with COVID-19 lockdown restrictions in a diverse metropolitan county.

Methods

Data were extracted from local police blotters and mapping engines in Orange County, California (United States), documenting police-reported DV assault. All incidents were coded for time to examine the time course of DV among other types of assault, allowing for a longitudinal view of incidents over a 66-week window. Changepoint analyses were used to determine whether and when DV assaults changed when mapped with coinciding tightening or loosening of restrictions county-wide. Piecewise regression analyses evaluated whether any detected fluctuations were statistically meaningful.

Results

In Santa Ana, rates saw a small but significant spike in the week following the first major lockdown in March 2020 (b = .04, SE = .02, t = 2.37, p = .01), remaining stable at this higher level thereafter (b = -.003, SE = .003, t = -1.29, p = .20). In Anaheim, no meaningful change in DV assault rates was observed at any time interval.

Conclusion

Results suggest that surges in DV vary between communities and that systemic issues may set the stage for the surge of an already endemic problem.
Performance of radiomics models derived from different CT reconstruction parameters for lung cancer risk prediction
Authors: Zhang Rui , Shi Jie , Liu Siyun , Chen Bojiang , Li Weimin
Published: April 2023

Background

This study analysed the performance of radiomics features extracted from computed tomography (CT) images with different reconstruction parameters in differentiating malignant and benign pulmonary nodules.

Methods

We evaluated routine chest CT images acquired from 148 participants with pulmonary nodules, which were pathologically diagnosed during surgery in West China Hospital, including a 5 mm unenhanced lung window, a 5 mm unenhanced mediastinal window, a 5 mm contrast-enhanced mediastinal window and a 1 mm unenhanced lung window. The pulmonary nodules were segmented, and 1409 radiomics features were extracted for each window. Then, we created 15 cohorts consisting of single windows or multiple windows. Univariate correlation analysis and principal component analysis were performed to select the features, and logistic regression analysis was performed to establish models for each cohort. The area under the curve (AUC) was applied to compare model performance.

Results

There were 75 benign and 73 malignant pulmonary nodules, with mean diameters of 18.63 and 19.86 mm, respectively. For the single-window setting, the AUCs of the radiomics model from the 5 mm unenhanced lung window, 5 mm unenhanced mediastinal window, 5 mm contrast-enhanced mediastinal window and 1 mm unenhanced lung window were 0.771, 0.808, 0.750, and 0.771 in the training set and 0.711, 0.709, 0.684, and 0.674 in the test set, respectively. Regarding the multiple-window setting, the radiomics model based on all four windows showed an AUC of 0.825 in the training set and 0.743 in the test set. Statistically, the 15 models demonstrated comparable performances (P > 0.05).

Conclusion

A single chest CT window was acceptable in predicting the malignancy of pulmonary nodules, and additional windows did not statistically improve the performance of the radiomics models. In addition, slice thickness and contrast enhancement did not affect the diagnostic performance.
Global trends in research on extracorporeal shock wave therapy (ESWT) from 2000 to 2021
Authors: Zhang Xinyu , Ma Yuewen
Published: April 2023

Background

This study intended to analyze the application of extracorporeal shock wave therapy in medicine and to evaluate the quality of related literature.

Methods

All publications were extracted from 2000 to 2021 from the Web of Science Core Collection (WoSCC). The literature characteristics were depicted by VOSviewer (version 1.6.15) and the online bibliometric website (http://bibliometric.com/). The future trends and hotspots were conducted by Bibliographic Item Co-occurrence Matrix Builder (version 2.0) and gCLUTO software.

Results

We analyzed 1774 articles corresponding to the criteria for ESWT publications from 2000 to 2021. Most studies were conducted within the United States and China which besides have the most cooperation. The most published research institutions are Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, and Kaohsiung Medical University. Six research hotspots were identified by keyword clustering analysis: Cluster0: The effects of ESWT on muscle spasticity; Cluster1: The application of ESWT in osteoarthritis (OA); Cluster2: Therapeutic effect of ESWT on tendon diseases; Cluster3: Early application of ESWT/ESWL in urolithiasis; Cluster4: The Role of angiogenesis in ESWT and the efficiency of ESWT for penile disease; Cluster5: The Special value of radial extracorporeal shock wave therapy (rESWT).

Conclusions

A comprehensive and systematic bibliometric analysis of ESWT was conducted in our study. We identified six ESWT-related research hotspots and predicted future research trends. With the gradual increase of research on ESWT, we find that ESWT is used more and more extensively, such in musculoskeletal disease, bone delay union, neurological injury, andrology disorders, lymphedema, and so on. In addition, the mechanism is not destructive damage, as initially thought, but a restorative treatment. Furthermore, delayed union, cellulite, burn, and diabetic foot ulcers may be the future direction of scientific study.
The predictive value of pretreatment hemoglobin-to-platelet ratio on osteoradionecrosis incidence rates of locally advanced nasopharyngeal cancer patients managed with concurrent chemoradiotherapy
Authors: Yilmaz Busra , Somay Efsun , Topkan Erkan , Kucuk Ahmet , Pehlivan Berrin , Selek Ugur
Published: April 2023

Background

This retrospective study aimed to investigate whether the pretreatment hemoglobin-to-platelet ratio (HPR) could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (C-CRT) for locally advanced nasopharyngeal carcinoma (LA-NPC).

Methods

ORN cases were reported from the records of LA-NPC patients who had oral examinations before and after C-CRT. The pretreatment HPR values were calculated on the first day of C-CRT. The connection between HPR values and ORN occurrences was determined using receiver operating characteristic curve analysis. The primary endpoint was the relationship between the pretreatment HPR values and post-C-CRT ORN incidence rates, while secondary endpoints included the identification of other putative ORN risk factors.

Results

We distinguished 10.9% incidences of ORN during the post-C-CRT follow-up period among 193 LA-NPC patients. The optimal cutoff for pre-C-CRT HPR was 0.48 that grouped the patients into two HPR groups with fundamentally different post-C-CRT ORN incidence rates: Group 1: HPR ≤ 0.48 (N = 60), and Group 2: HPR > 0.48 (N = 133). The comparative analysis indicated a significantly higher ORN incidence in HPR ≤ 0.48 group (30%; P < 0.001). The other factors associated with meaningfully increased ORN rates included the presence of pre-C-CRT ≥ 5 teeth extractions, mandibular volume receiving ≥ 64 Gy, post-C-CRT tooth extractions, mean mandibular dose ≥ 50.6 Gy, and C-CRT to tooth extraction interval > 5.5 months.

Conclusion

Low pretreatment HPR levels were independently and unequivocally linked to significantly increased incidence of ORN post-C-CRT. Pre-C-CRT HPR levels may be used to estimate the incidence of ORN and be useful for taking preventive and therapeutic measures in these patients such as monitoring oral hygiene with strict follow-up, avoidance of unnecessary tooth extractions, particularly after C-CRT, and use of more rigorous mandibular RT dose limits.
Assessment of a training project of English as a media of instruction(EMI) using Kirkpatrick model
Authors: Zhao Wenlan , Liu Zixian , Wang Tong , Yin Xiaohan , Sun Yanchun , Zhang Xuemei , Yang Hui
Published: April 2023

Background

English as a Media of Instruction (EMI) teacher development project is based upon the framework for teacher Continuing Professional Development (CPD) and aims to effectively improve both the confidence and overall capacity of EMI lecturers. Kunming Medical University(KMU) conducted the EMI training project to improve teachers’ competence for MBBS education. This study aimed to assess teachers’ changes following the implementation of this training project, via the Kirkpatrick evaluation model.

Methods

A total of trainees (n = 84) were invited as the research objects. The effects of the EMI training project implemented in KMU were evaluated in terms of the reaction, learning, and behavior dimensions based on the Kirkpatrick model. The self-administered online anonymous questionnaires and observations of participants’ EMI lectures were administered to all participants to collect the data. Furthermore, to understand participants’ perceptions of the management and trainers of the training project, some open-ended questions were required to answer.

Results

Based on 1–3 level of the Kirkpatrick model, all participants were highly satisfied with the EMI training implementation on the reaction level, and expressed positive comments about the management of the training and trainers. On the learning level, participants’ scores on awareness of EMI teaching techniques increased significantly(t = 7.122, P < 0.001)with the training process. Concerning the behavior level, the participant’s confidence as an EMI instructor increased dramatically at end of the whole training(p < 0.001). Moreover, trainees had applied some EMI skills in class and would like to make some commitment to implement learner-centered learning, to do more practice on EMI techniques.

Conclusion

The findings of this study confirm that EMI training has an effective impact on the competence and confidence of participants as EMI instructors at levels 1–3 of the Kirkpatrick evaluation model. This training may be a potentially beneficial effect on the teaching quality of MBBS education.
Unpopular medical specialties: exploring the concept that “the customer knows best”
Authors: Weissman Charles , Avidan Alexander , Tandeter Howard , Zisk Rony Rachel Yaffa
Published: April 2023

Background

Healthcare systems often face shortages of certain medical specialists due to lack of interest among medical students. We questioned a common “one solution fits all” approach to this problem which involves monetary incentives to lure students to these specialties. Instead, we used the marketing principle the “consumer knows best” to explore ways of elucidating the reasons and proposing solutions for such shortages.

Methods

A convenience sample of Israeli 6th-year medical students and interns completed questionnaires to determine why they thought three specialties (geriatrics, anesthesiology, emergency medicine) were unpopular and their ideas on increasing their appeal.

Results

119 6th-year students and 84 interns completed questionnaires. Geriatrics was reported having a problematic patient population; not being interesting and challenging; and not considered prestigious by colleagues and the populace. This contrasts with emergency medicine which, although considered prestigious, has difficult working conditions both during and after residency accompanied by much pressure at work. Although, improvements in lifestyle and remuneration were thought by students and interns as possibly making these specialties more attractive, reducing the pressure at work and decreasing on-call obligations were designated by the students/interns as ways to increase emergency medicine’s and anesthesiology’s appeal. Half the students replied that anesthesiology would be more appealing if work was in shifts (< 16 h), while 60% replied so for emergency medicine and only 18% for geriatrics. 90% of students reported that control over lifestyle would make emergency medicine more attractive while 55% and 48% replied positively for anesthesiology and geriatrics, respectively.

Conclusions

Using the concept “consumer knows best” provided additional insight into the specialty selection process. Students/interns have specialty-specific opinions as to why some specialties are unpopular. Their ideas about attracting more students to these specialties were also specialty-dependent, i.e. “one solution does not fit all”. These observations render problematic a single solution aimed at ameliorating the workforce shortages of multiple specialties. Instead, these results advocate a differential approach wherein the lack of appeal of each unpopular specialty is analyzed individually and the students’/interns’ (the “consumers”) ideas sought resulting in solutions tailored to address each specialty’s lack of attractiveness.

Trial Registration

None.
Behavioural change interventions encouraging clinicians to reduce carbon emissions in clinical activity: a systematic review
Authors: Batcup Carys , Breth-Petersen Matilde , Dakin Thomas , Barratt Alexandra , McGain Forbes , Newell Ben R. , Pickles Kristen
Published: April 2023

Background

Clinical activity accounts for 70–80% of the carbon footprint of healthcare. A critical component of reducing emissions is shifting clinical behaviour towards reducing, avoiding, or replacing carbon-intensive healthcare. The objective of this systematic review was to find, map and assess behaviour change interventions that have been implemented in healthcare settings to encourage clinicians to reduce greenhouse gas emissions from their clinical activity.

Methods

Studies eligible for inclusion were those reporting on a behaviour change intervention to reduce carbon emissions via changes in healthcare workplace behaviour. Six databases were searched in November 2021 (updated February 2022). A pre-determined template was used to extract data from the studies, and risk of bias was assessed. The behaviour change techniques (BCTs) used in the interventions were coded using the BCT Taxonomy.

Results

Six full-text studies were included in this review, and 14 conference abstracts. All studies used a before-after intervention design. The majority were UK studies (n = 15), followed by US (n = 3) and Australia (n = 2). Of the full-text studies, four focused on reducing the emissions associated with anaesthesia, and two aimed at reducing unnecessary test ordering. Of the conference abstracts, 13 focused on anaesthetic gas usage, and one on respiratory inhalers. The most common BCTs used were social support, salience of consequences, restructuring the physical environment, prompts and cues, feedback on outcome of behaviour, and information about environmental consequences. All studies reported success of their interventions in reducing carbon emissions, prescribing, ordering, and financial costs; however, only two studies reported the magnitude and significance of their intervention’s success. All studies scored at least one item as unclear or at risk of bias.

Conclusion

Most interventions to date have targeted anaesthesia or pathology test ordering in hospital settings. Due to the diverse study outcomes and consequent inability to pool the results, this review is descriptive only, limiting our ability to conclude the effectiveness of interventions. Multiple BCTs were used in each study but these were not compared, evaluated, or used systematically. All studies lacked rigour in study design and measurement of outcomes.

Review registration

The study was registered on Prospero (ID number CRD42021272526) (Breth-Petersen et al., Prospero 2021: CRD42021272526).
Use of anti-viral therapies in hospitalised COVID-19 patients in the United Arab Emirates: a cost-effectiveness and health-care resource use analysis
Authors: Subhi Ahmad , Shamy Amin Mohamed El , Hussein Saeed Abdullah Mohammed , Jarrett James , Kozma Sam , Harfouche Camille , Al Dallal Sara
Published: April 2023

Background

This study attempts to estimate the cost-effectiveness of the antiviral remdesivir, as recommended in the 2021 COVID treatment guidelines for the United Arab Emirates, compared to standard of care (SOC), but also favipiravir (FAVI), which was also recommended for the treatment of hospitalized COVID patients.

Methods

A cost-effectiveness model was built using published efficacy data for RDV, FAVI and SOC as well as local epidemiology data. The outcomes measured included hospital bed days averted, mortality, costs and cost per outcome over one year. One-way, probabilistic and scenario analyses were undertaken to reflect uncertainty in the estimates.

Results

When modelled over one year, the results indicated that treatment of adults in need of supplemental oxygen with RDV + SOC could result in 11,338 fewer general ward bed days, 7,003 fewer ICU days and 5,451 fewer ICU + MIV bed days compared to SOC alone and similar results when compared with FAVI + SOC. The model results also showed that there were 374 fewer deaths associated with the use of RDV + SOC compared to SOC alone. The model also estimates substantial potential cost-savings associated with RDV + SOC treatment compared with SOC alone (USD 3,454 per patient). The results of the one-way sensitivity analysis showed that the model was sensitive to estimates of length of stay and the cost of hospitalization. Despite this, the model predicted cost-savings in all scenarios versus all comparators.

Conclusions

The model estimated that using RDV + SOC could result in substantial reductions in HCRU and cost savings regardless of the comparator. However, it should be noted that reliable clinical information on FAVI was limited therefore it is challenging to interpret these results. All the potential benefits modelled here for RDV + SOC can have implications not only for the health of the UAE population but for improving hospital capacity to deal with other conditions.
Attitudes and experiences with fentanyl contamination of methamphetamine: exploring self-reports and urine toxicology among persons who use methamphetamine and other drugs
Authors: Daniulaityte Raminta , Ruhter Lance , Juhascik Matthew , Silverstein Sydney
Published: April 2023

Background

There are growing concerns about illicitly manufactured fentanyl (IMF) contamination of methamphetamine. This study aims to characterize the lay views and experiences with IMF-contaminated methamphetamine (IMF/meth) and identify participants with unknown IMF exposures through urine toxicology analysis.

Methods

Between December-2019 and November-2021, structured interviews were conducted with 91 individuals who reported past 30-day use of methamphetamine and resided in Dayton, Ohio, USA. Lab-based urine toxicology analyses were conducted to identify fentanyl/analogs, methamphetamine, and other drugs. Bivariate analyses were conducted to identify characteristics associated with attitudes and experiences with IMF/meth, and unknown IMF exposures.

Results

The majority (95.6%) of the study participants were non-Hispanic white, and 52.7% were female. Past 30-day use of methamphetamine was reported on a mean of 18.7 (SD 9.1) days, and 62.6% also reported past 30-day use of heroin/IMF. Most (76.9%) had a history of an unintentional drug-related overdose, but 38.5% rated their current risk for an opioid overdose as none. Besides fentanyl (71.9%), toxicology analysis identified nine fentanyl analogs/metabolites (e.g., 42.7% acetyl fentanyl, 19.0% fluorofentanyl, 5.6% carfentanil), and 12.4% tested positive for Xylazine. The majority (71.4%) believed that IMF/meth was common, and 59.3% reported prior exposures to IMF/meth. 11.2% tested positive for IMF but reported no past 30-day heroin/IMF use (unknown exposure to IMF). Views that IMF/meth was common showed association with homelessness (p = 0.04), prior overdose (p = 0.028), and greater perceived risk of opioid overdose (p = 0.019). Self-reported exposure to IMF/meth was associated with homelessness (p = 0.007) and obtaining take-home naloxone (p = 0.025). Individuals with unknown IMF exposure (test positive for IMF, no reported past 30-day heroin/IMF use) were older (49.9 vs. 41.1 years, p < 0.01), and reported more frequent past 30-day use of methamphetamine (24.4 vs. 18.0 days, p < 0.05). They indicated lower perceived risk of opioid overdose (0.1 vs. 1.9, scale from 0 = “none” to 4 = “high,” p < 0.001).

Discussion

This study suggests a need for targeted interventions for people who use methamphetamine and expansion of drug checking and other harm reduction services.
The emerging role of lysine succinylation in ovarian aging
Authors: Le Meiling , Li Jia , Zhang Dalei , Yuan Yuan , Zhou Chong , He Jinxia , Huang Jian , Hu Liaoliao , Luo Tao , Zheng Liping
Published: April 2023

Background

Ovarian aging is a process of decline in its reserve leading to ovary dysfunction and even reduced health quality in offspring. However, aging-related molecular pathways in the ovary remain obscure. Lysine succinylation (Ksuc), a newly post-translational modification (PTM), has been found to be broadly conserved in both eukaryotic and prokaryotic cells, and associated with multiple pathophysiological processes. There are no relevant reports revealing a link between the molecular mechanisms of ovarian aging and Ksuc.

Methods

The level of Ksuc in ovaries of aged and premature ovarian insufficiency (POI) mice were detected by immunoblotting and immunohistochemical. To further explore the role of Ksuc in ovarian aging, using in vitro mouse ovary tissue culture and an in vivo mouse model with changed Ksuc level.

Results

Increased Ksuc in ovaries of aged and POI mice and distribution of Ksuc in various types of mice ovarian cells and the high level of Ksuc in granulosa cells (GCs) were revealed. Histological assessments and hormone levels analyses showed that the high Ksuc level down-regulated the ovarian index and the anti-Müllerian hormone (AMH) and estrogen levels, and increased follicular atresia. Moreover, in the high Ksuc groups, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) intensities and the expression of Cleaved-caspase-3 increased and the expression of B-cell lymphoma-2 (Bcl-2) decreased together with positively-expressed P21, an aging-related marker. These results suggest that ovarian aging is likely associated with alteration in Ksuc.

Conclusion

The present study has identified Ksuc in mouse ovary and found that high Ksuc level most likely contributes to ovarian aging which is expected further investigation to provide new information for delaying physiological ovarian aging and treating pathological ovarian aging.
Brassicasterol inhibits hepatitis B virus-associated hepatocellular carcinoma development via suppression of AKT signaling pathway
Authors: Zeng Jindi , Wu Jiancheng , Pang Shuijiao , Wang Feifei , Yu Xin , Zhang Shouhua , Zeng Junquan , Yan Jinlong , Lian Jianping
Published: April 2023

Background

Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) does not respond well to current treatment options like sorafenib, and there is an urgent need for developing therapeutical strategies for HBV + HCC. Brassicasterol has previously shown anti-cancer and anti-viral activities, however, its value against HBV + HCC remains to be explored.

Methods

The inhibitory effect of brassicasterol and sorafenib was evaluated on HBV + HCC cell lines and xenograft mouse model. The cytotoxicity of brassicasterol on normal liver cells were measured by LDH assay. AKT agonist was used to identify the targeted signaling pathway by brassicasterol.

Results

Brassicasterol induced HBV + HCC cell death in a both dose-dependent and time-dependent manner, and such inhibition was more potent than sorafenib. Brassicasterol did not show apparent cytotoxicity to normal liver cells. Xenograft mouse model further confirmed the inhibitory effect of brassicasterol on the growth of HBV + HCC. Furthermore, signaling pathway analysis showed that brassicasterol-treated HBV + HCC cells had decreased level of phosphor-AKT expression while the addition of AKT agonist could counteract the inhibitory effect of brassicasterol on HCC, indicating that brassicasterol suppressed AKT pathway to exhibit anti-cancer activity in HBV + HCC cells. In addition, brassicasterol showed similar levels of inhibition on HBV− and HBV + HCC cells.

Conclusion

Brassicasterol possesses anti-cancer activity against HCC through the downregulation of AKT pathway and such activity is independent of HBV infection.
Regulation of ERα-dependent breast cancer metastasis by a miR-29a signaling
Authors: Lü Jinhui , Zhao Qian , Guo Yuefan , Li Danni , Xie Heying , Liu Cuicui , Hu Xin , Liu Suling , Hou Zhaoyuan , wei Xunbin , Zheng Deyou , Pestell Richard G. , Yu Zuoren
Published: April 2023

Malignant breast cancer (BC) remains incurable mainly due to the cancer cell metastasis, which is mostly related to the status of Estrogen receptor alpha (ERα). However, our understanding of the mechanisms through which ERα regulates cancer cell metastasis remains limited. Here we identified a miR-29a-PTEN-AKT axis as a downstream signaling pathway of ERα governing breast cancer progression and metastasis. Two estrogen response element (ERE) half sites were identified in the promoter and enhancer regions of miR-29a, which mediated transcriptional regulation of miR-29a by ERα. Low level of miR-29a showed association with reduced metastasis and better survival in ERα+ luminal subtype of BC. In contrast, high level of miR-29a was detected in ERα- triple negative breast cancer (TNBC) in association with distant metastasis and poor survival. miR-29a overexpression in BC tumors increased the number of circulating tumor cells and promoted lung metastasis in mice. Targeted knockdown of miR-29a in TNBC cells in vitro or administration of a nanotechnology-based anti-miR-29a delivery in TNBC tumor-bearing mice in vivo suppressed cellular invasion, EMT and lung metastasis. PTEN was identified as a direct target of miR-29a, inducing EMT and metastasis via AKT signaling. A small molecular inhibitor of AKT attenuated miR-29a-induced EMT. These findings demonstrate a novel mechanism responsible for ERα-regulated breast cancer metastasis, and reveal the combination of ERα status and miR-29a levels as a new risk indicator in BC.
Racial differences in RAD51 expression are regulated by miRNA-214-5P and its inhibition synergizes with olaparib in triple-negative breast cancer
Authors: Mani Chinnadurai , Acharya Ganesh , Saamarthy Karunakar , Ochola Damieanus , Mereddy Srinidhi , Pruitt Kevin , Manne Upender , Palle Komaraiah
Published: April 2023

Background

Triple-negative breast cancer (TNBC) affects young women and is the most aggressive subtype of breast cancer (BC). TNBCs disproportionally affect women of African-American (AA) descent compared to other ethnicities. We have identified DNA repair gene RAD51 as a poor prognosis marker in TNBC and its posttranscriptional regulation through microRNAs (miRNAs). This study aims to delineate the mechanisms leading to RAD51 upregulation and develop novel therapeutic combinations to effectively treat TNBCs and reduce disparity in clinical outcomes.

Methods

Analysis of TCGA data for BC cohorts using the UALCAN portal and PrognoScan identified the overexpression of RAD51 in TNBCs. miRNA sequencing identified significant downregulation of RAD51-targeting miRNAs miR-214-5P and miR-142-3P. RT-PCR assays were used to validate the levels of miRNAs and RAD51, and immunohistochemical and immunoblotting techniques were used similarly for RAD51 protein levels in TNBC tissues and cell lines. Luciferase assays were performed under the control of RAD51 3’-UTR to confirm that miR-214-5P regulates RAD51 expression. To examine the effect of miR-214-5P-mediated downregulation of RAD51 on homologous recombination (HR) in TNBC cells, Dr-GFP reporter assays were performed. To assess the levels of olaparib-induced DNA damage responses in miR-214-5P, transfected cells, immunoblots, and immunofluorescence assays were used. Furthermore, COMET assays were used to measure DNA lesions and colony assays were performed to assess the sensitivity of BRCA-proficient TNBC cells to olaparib.

Results

In-silico analysis identified upregulation of RAD51 as a poor prognostic marker in TNBCs. miRNA-seq data showed significant downregulation of miR-214-5P and miR-142-3P in TNBC cell lines derived from AA women compared to Caucasian-American (CA) women. miR-214-5P mimics downregulated RAD51 expression and induces HR deficiency as measured by Dr-GFP assays in these cell lines. Based on these results, we designed a combination treatment of miR-214-5P and olaparib in HR-proficient AA TNBC cell lines using clonogenic survival assays. The combination of miR-214-5P and olaparib showed synergistic lethality compared to individual treatments in these cell lines.

Conclusions

Our studies identified a novel epigenetic regulation of RAD51 in TNBCs by miR-214-5P suggesting a novel combination therapies involving miR-214-5P and olaparib to treat HR-proficient TNBCs and to reduce racial disparity in therapeutic outcomes.
ACT-Discover: identifying karyotype heterogeneity in pancreatic cancer evolution using ctDNA
Authors: Huebner Ariana , Black James R. M. , Sarno Francesca , Pazo Roberto , Juez Ignacio , Medina Laura , Garcia-Carbonero Rocio , Guillén Carmen , Feliú Jaime , Alonso Carolina , Arenillas Carlota , Moreno-Cárdenas Ana Belén , Verdaguer Helena , Macarulla Teresa , Hidalgo Manuel , McGranahan Nicholas , Toledo Rodrigo A.
Published: April 2023

Background

Liquid biopsies and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution.

Methods

To interrogate the role of SCNAs in pancreatic adenocarcinoma cancer evolution, we applied whole-exome sequencing of 55 longitudinal cell-free DNA (cfDNA) samples taken from 24 patients (including 8 from whom a patient-derived xenograft (PDX) was derived) with metastatic disease prospectively recruited into a clinical trial. We developed a method, Aneuploidy in Circulating Tumour DNA (ACT-Discover), that leverages haplotype phasing of paired tumour biopsies or PDXs to identify SCNAs in cfDNA with greater sensitivity.

Results

SCNAs were observed within 28 of 47 evaluable cfDNA samples. Of these events, 30% could only be identified by harnessing the haplotype-aware approach leveraged in ACT-Discover. The exceptional purity of PDX tumours enabled near-complete phasing of genomic regions in allelic imbalance, highlighting an important auxiliary function of PDXs. Finally, although the classical model of pancreatic cancer evolution emphasises the importance of early, homogenous somatic events as a key requirement for cancer development, ACT-Discover identified substantial heterogeneity of SCNAs, including parallel focal and arm-level events, affecting different parental alleles within individual tumours. Indeed, ongoing acquisition of SCNAs was identified within tumours throughout the disease course, including within an untreated metastatic tumour.

Conclusions

This work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy.
The role of Iran's context for the development of health technology assessment: challenges and solutions
Authors: Behzadifar Meysam , Behzadifar Masoud , Saran Maryam , Shahabi Saeed , Bakhtiari Ahad , Azari Samad , Bragazzi Nicola Luigi
Published: April 2023

Health technology assessment (HTA) is a comprehensive and structured evaluation that aims to analyze the potential impacts of health technologies, including medical devices, diagnostic tools, pharmaceuticals, and public health interventions. Its purpose is to provide policymakers with evidence-based information to inform decisions related to the utilization and implementation of these technologies. HTA allows for the comparison of various scenarios related to a technology across a wide range of factors. This can aid in the creation of an essential drug list and health benefits package that is tailored to the actual needs of the community within a given healthcare system. In the present paper, we review the role of Iran's context for the development of HTA, in terms of challenges and solutions.
Longitudinal trends and determinants of stunting among children aged 1–15 years
Authors: Wake Senahara Korsa , Zewotir Temesgen , Lulu Kebede , Fissuh Yemane Hailu
Published: April 2023

Background

Stunting increases morbidity and mortality, hindering mental development and influencing cognitive capacity of children. This study aimed to examine the trends and determinants of stunting from infancy to middle adolescence in four countries: Ethiopia, India, Peru, and Vietnam.

Methods

A 15-year longitudinal data on the trends of stunting were obtained from the Young Lives cohort study. The study includes 38,361 observations from 4 countries. A generalized mixed-effects model was adopted to estimate the determinant of stunting.

Results

The patterns of stunting in children from aged 1 to 15 years have declined from an estimated 30% in 2002 to 20% in 2016. Stunting prevalence varied among four low- and middle-income countries with children in Ethiopia, India, and Peru being more stunted compared to children in Vietnam. The highest stunted was recorded in India and the lowest was recorded in Vietnam. In all four countries, the highest prevalence of severe stunting was observed in 2002 and moderate stunting was observed in 2006. Parents’ education level played a significance role in determining a child stunting. Children of uneducated parents were shown to be at a higher risk of stunting.

Conclusion

Disparities of stunting were observed between- and within-country of four low- and middle-income with the highest prevalence recorded in low-income country. Child stunting is caused by factors related to child’s age, household wealth, household size, the mother’s and father’s education level, residence area and access to save drinking water.