bluuebunny/crossref_metadata_2025 huggingface dataset:
A multicenter real-world evidence study in the Swiss treatment landscape of chronic myeloid leukemia
Authors: Cantoni Nathan , Sommavilla Roberto , Seitz Patrick , Kulenkampff Elisabeth , Kahn Stefan , Lambert Jean-François , Schmidt Adrian , Zenhaeusern Reinhard , Balabanov Stefan
Published: November 2022

Background

The real-world experience of Swiss chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) is largely unknown, in particular with regard to achievement of response per European Leukemia Net (ELN) criteria and adherence to ELN recommendations.

Methods

This was a retrospective, non-interventional, multicenter chart review of patients with newly diagnosed CML who had received first-line TKI and were solely treated with TKIs between 2010 and 2015, with a minimum follow-up of 18 months, at six Swiss hospitals. Effectiveness was evaluated according to ELN 2013 milestone achievements at 3, 6, 12 and 18 months, and at last follow-up.

Results

Data from 63 patients (56% men; median age at diagnosis 55 years) were collected (first-line imatinib [n = 27], nilotinib [n = 27], dasatinib [n = 8], or ponatinib [n = 1]). TKI switches (49 times) and dosing changes (165 times) due to intolerance or insufficient response were frequent. Compared with patients receiving first-line imatinib, a higher proportion of patients receiving first-line nilotinib or dasatinib achieved optimal response at all timepoints, irrespective of subsequent TKI therapy, and a higher proportion of patients treated with first-line nilotinib and dasatinib reached deep molecular response (BCR-ABL1IS ≤ 0.01%) at 18 months (42 and 38%, respectively, versus 27%). Patients who received nilotinib or dasatinib switched therapies less frequently than patients treated with imatinib, irrespective of subsequent TKI therapy.

Conclusions

Although patient numbers were small, this real-world evidence study with patients with CML confirms that ELN guidelines are generally implemented in Swiss clinical practice, with a large proportion of patients achieving ELN 2013 milestones. While TKI use involved all inhibitors approved at the time of the study, an unexpectedly high number of TKI therapy switches suggests a clear difference in TKI use between registration trials and clinical practice.
Combined phacoemulsification surgery and intravitreal triamcinolone injection versus stand-alone surgery in patients with type 2 diabetes: a prospective randomized trial
Authors: Zaher Addeen Sarah , Shaddoud Iyad
Published: November 2022

Background

We would assess the efficacy of intravitreal injection of triamcinolone acetonide IVTA combined with standard phacoemulsification on the central subfield macular thickness (CSMT), the progression of diabetic retinopathy (DR), and the corrected distant visual acuity (CDVA) in type 2 diabetic patients.

Methods

In this prospective single-blinded randomized clinical trial we recruited patients with type 2 diabetes who were eligible for cataract surgery. The patients were randomly assigned to two groups. The case group received an intravitreal IVTA at the end of phacoemulsification, and the control group had routine surgery. CSMT, progression of DR, CDVA, IOP, and adverse events including endophthalmitis were compared between the groups preoperatively and at 1, 3, and 6 months postoperatively.

Results

Among a total of 66 patients that were treated within the study period, 50 patients were included in the final analysis. The case group comprised 21 eyes, and the control group included 29 eyes. Regression models and corrected ANOVA test for repeated measures showed a significant reduction in CSMT at 3 and 6 months postoperatively, which was most significant when the preoperative CSMT was ≥300 μm, with a cut-off value of 347.3 μm in the case group (p < 0.000). DR progression was halted in the case group at 6 months with 52.38% of patients having their DR classified as moderate (P = 0.012). CDVA was significantly improved from baseline 6/60 (logMAR 1.0) pre-op to 6/6 (logMAR 0.00) at 6 months post-op in the case group, and from baseline 6/120 (logMAR 1.3) pre-op to 6/12 (logMAR 0.3) at 6 months post-op in the control group. The gain in visual acuity was significantly higher in the case group at all study points (p < 0.001). No significant rise in IOP was observed at any study point in both groups (p = 0.23 > 0.05). No endophthalmitis was recorded.

Conclusions

Diabetic patients benefit significantly from cataract surgery. This study supports IVTA injection at the end of phacoemulsification in diabetic patients. Triamcinolone is an affordable (which is of particular importance in low-income countries as per our setting), and relatively safe “phaco-enhancer”.

Trial registration

NCT05413330. Initial release 10/06/2022. Unique Protocol ID: UDMS-Opthal-01-2022.
Psychometric properties of the of the Persian version of the Coping Assessment for Bereavement and Loss Experiences (CABLE)
Authors: Ebadi Abbas , Seraji Asal , Farahani Maryam Farmahini , Sharif Nia Hamid
Published: November 2022

Background and aim

The loss of a loved one through death is practically an inevitable part of the human experience. However, not all grieving people cope with this blow in the same way. One of the factors that may differentiate the grieving reactions of mourners in the face of this lesion is the strategies that the person uses in this situation to adapt and manage the situation. A valid and reliable tool is also needed to measure and evaluate coping strategies. The aim of this study was to translate and determine the characteristics of psychological tools for measuring coping with experiences of grief and loss (28 items) in people living in Tehran.

Materials and methods

This is a methodological study with a descriptive cross-sectional design that after obtaining written permission from the original developer and according to the WHO protocol, the Persian version of the questionnaire was completed by 480 people who experienced mourn in Tehran in February 2021 to October 2021. Then, the Face validity, Content validity and Construct validity of questionnaire were assessed. Cronbach’s alpha coefficient, McDonald’s omega and Test-retest were used to determine the reliability.

Results

Cronbach’s alpha for all items was 0.91 and intra-class correlation coefficient was 0.86, both of which indicate the reliability of the Persian version of the CABLE tool. Based on exploratory factor analysis, maximum likelihood (n = 260) and confirmatory factor analysis (n = 220) six factors were identified. Factors can explain 50% of the total variance observed. The model had an acceptable fit: GFI: 0.88, CFI: 0.96, IFI: 0.96, NFI: 0.92, PNFI: 0.82, RAMSEA: 0.058, CMIN / DF: 2.37 RMR: 0.056. Internal consistency and construct validity of the questionnaire were confirmed.

Conclusion

The findings of the present study indicate that the Persian version of CABLE has the appropriate validity and reliability to assess the compliance with the experiences of grief and loss in Persian population.
In-hospital predictors of post-stroke depression for targeted initiation of Selective Serotonin Reuptake Inhibitors (SSRIs)
Authors: Yi Julie , Lu Justin , Yang Annie , Marsh Elisabeth Breese
Published: November 2022

Background

Although SSRIs are no longer widely prescribed for post-stroke motor recovery, fluoxetine demonstrated beneficial effects on post-stroke depression (PSD). Given the potential side effects of SSRIs, targeted initiation among individuals at highest risk for PSD warrants consideration. While previous studies have identified stroke severity and psychiatric history as factors associated with PSD, its predictability remains unknown. In this study, we investigate inpatient predictive factors to better identify individuals who might derive the most benefit from targeted initiation of SSRIs.

Methods

We performed a retrospective analysis of a prospectively-collected registry of adult patients presenting with acute ischemic stroke to a tertiary referral urban academic comprehensive stroke center between 2016–2020. Patients were seen 4–6 weeks post-discharge and administered the PHQ-9 (Patient Health Questionnaire-9) to screen for PSD (PHQ-9 ≥ 5). Demographics, history of depression, stroke severity, and inpatient PHQ-9 scores were abstracted. Logistic regression was used to determine factors associated with PSD and an ROC analysis determined the predictability of PSD in the inpatient setting.

Results

Three hundred seven individuals were administered the PHQ-9 at follow-up (mean age 65.5 years, 52% female). History of depression (OR = 4.11, 95% CI: 1.65–10.26) and inpatient PHQ-9 score (OR = 1.17, 95% CI: 1.06–1.30) were significantly associated with PSD. Stroke severity, marital status, living alone, employment, and outpatient therapy were not associated with PSD. The ROC curve using a positive inpatient PHQ-9 achieved an area under the curve (AUC) of 0.65 (95% CI: 0.60–0.70), while the AUC was 0.72 (95% CI: 0.66–0.77) after adding history of depression.

Conclusions

History of depression and a positive inpatient PHQ-9 appear to be most strongly predictive of long-term PSD. Initiating SSRIs only in those individuals at highest risk for PSD may help reduce the burden of stroke recovery in this targeted population while minimizing adverse side effects.
Amplified effect of social vulnerability on health inequality regarding COVID-19 mortality in the USA: the mediating role of vaccination allocation
Authors: Chen Ying , Zhang Lanwei , Li Tenglong , Li Li
Published: November 2022

Background

Vaccination reduces the overall burden of COVID-19, while its allocation procedure may introduce additional health inequality, since populations characterized with certain social vulnerabilities have received less vaccination and been affected more by COVID-19. We used structural equation modeling to quantitatively evaluate the extent to which vaccination disparity would amplify health inequality, where it functioned as a mediator in the effect pathways from social vulnerabilities to COVID-19 mortality.

Methods

We used USA nationwide county (n = 3112, 99% of the total) level data during 2021 in an ecological study design. Theme-specific rankings of social vulnerability index published by CDC (latest data of 2018, including socioeconomic status, household composition & disability, minority status & language, and housing type & transportation) were the exposure variables. Vaccination coverage rate (VCR) during 2021 published by CDC was the mediator variable, while COVID-19 case fatality rate (CFR) during 2021 published by John Hopkinson University, the outcome variable.

Results

Greater vulnerabilities in socioeconomic status, household composition & disability, and minority status & language were inversely associated with VCR, together explaining 11.3% of the variance of VCR. Greater vulnerabilities in socioeconomic status and household composition & disability were positively associated with CFR, while VCR was inversely associated with CFR, together explaining 10.4% of the variance of CFR. Our mediation analysis, based on the mid-year data (30th June 2021), found that 37.6% (mediation/total effect, 0.0014/0.0037), 10% (0.0003/0.0030) and 100% (0.0005/0.0005) of the effects in the pathways involving socioeconomic status, household composition & disability and minority status & language, respectively, were mediated by VCR. As a whole, the mediation effect significantly counted for 30.6% of COVID-19 CFR disparity. Such a mediation effect was seen throughout 2021, with proportions ranging from 12 to 32%.

Conclusions

Allocation of COVID-19 vaccination in the USA during 2021 led to additional inequality with respect to COVID-19 mortality. Viable public health interventions should be taken to guarantee an equitable deployment of healthcare recourses across different population groups.
Value of sputum Gram stain, sputum culture, and bronchoalveolar lavage fluid Gram stain in predicting single bacterial pathogen among children with community-acquired pneumonia
Authors: Zhang Ruimu , Wu Yue , Deng Guangcheng , Deng Jikui
Published: November 2022

Background

Currently, the microbial etiology of community-acquired pneumonia in children remains challenging. While Gram stain and sputum culture are commonly used to detect bacterial pathogens, it is unclear whether these approaches can predict single pathogen from bronchoalveolar lavage fluid (BALF) culture.

Methods

A retrospective study involving 287 children hospitalized for pneumonia was conducted. Sputum specimens were collected on admission; and BALF specimens were collected within 24 h after admission. Taking BALF culture as the reference standard, the sensitivity and specificity of Sputum Gram stain (SGS), sputum culture, and BALF Gram stain (BGS) were calculated. The agreement between these approaches and BALF culture was compared using kappa statistics.

Results

For SGS, the specificity was 23%. The overall sensitivity was 70%, including 87% for Gram-positive (G+) cocci, 56% for Gram-negative (G-) cocci, and 50% for G-bacilli. For sputum culture, the specificity was 70%. The overall sensitivity was 64%, including 71% for Streptococcus pneumoniae, 71% for Moraxella catarrhalis, and 64% for Haemophilus influenzae. For BGS, the specificity was 71%. The overall sensitivity was 60%, including 77% for G+cocci, 38% for G-cocci, and 44% for G-bacilli. While SGS had poor agreement with BALF culture, both sputum culture and BGS had moderate agreement with BALF culture.

Conclusions

Both sputum culture and BGS are helpful in predicting single bacterial pathogen from BALF culture among children with community-acquired pneumonia. Sputum cultures and BGS can provide early clues for BALF pathogen when BALF culture results are pending or bronchoscopy is not performed.
Comparison between single-segment Isobar EVO dynamic stabilization and Isobar TTL dynamic stabilization in the treatment of lumbar degenerative diseases: a single center retrospective study over 4 years
Authors: Guan Jianbin , Liu Tao , Feng Ningning , Jiang Guozheng , Li Wenhao , Yang Kaitan , Zhao He , Yang Yongdong , Yu Xing
Published: November 2022

Objective

Posterior instrumented fusion is the most widely accepted surgical treatment for spinal stenosis and disc herniation. However, fusion can affect daily activities due to lumbar stiffness. In recent years, dynamic stabilization has been introduced to overcome the drawbacks of fusion, however, it is inconclusive whether dynamic stabilization requires the maintenance of a level of activity that is closer to the physiological state of activity for better clinical efficacy. The purpose of this study was to compare the effectiveness of dynamic stabilization with different levels of activity (Isobar EVO and TTL) in the treatment of spinal stenosis and disc herniation.

Methods

This study retrospectively reviewed 80 consecutive patients with lumbar degenerative diseases who were undergoing surgical treatment between March 2014 and July 2018. 41 patients (EVO group) and 39 patients (TTL group) underwent fenestrated decompression with Isobar EVO stabilization and Isobar TTL stabilization, respectively. Clinical outcomes, radiographic data, and postoperative complications were compared between the two groups.

Results

At an average follow-up of 52.23 ± 2.97 months, there were no significant differences in the oswestry disability index (ODI) (P > 0.05). The visual analog scale for back pain (VASback) and visual analog scale for the leg pain (VASleg) of the EVO group were lower compared with the TTL group (P < 0.05). The range of motion (ROM) of operated segments were significantly higher in the EVO group as compared to the TTL group (P < 0.05). The intervertebral space height (ISH) of upper adjacent segments were significantly higher in the EVO group as compared to the TTL group (P < 0.05). The overall complications were less in the EVO group, but the difference was not statistically significant (P > 0.05).

Conclusion

Both Isobar EVO dynamic stabilization and TTL dynamic stabilization can improve clinical outcomes of patients with spinal stenosis and disc herniation. Isobar EVO has advantages over Isobar TTL in terms of improving low back and leg pain, maintaining mobility of the operated segment, and preventing further degeneration of the upper adjacent segment.
Effect of training based on health belief model and behavioral intention on improving dental and oral self-care behavior in 9–12-year-old Iranian female students
Authors: Mohammadkhah Fatemeh , Ramezankhani Ali , Atashpoosh Abolfazl , Ahmady Moghadam Farzaneh , Bakhtiar Maryam , Khani Jeihooni Ali
Published: November 2022

Background

Training dental and oral health behaviors by using appropriate training models and theories is an important issue in preventing dental and oral diseases. the present study aimed to investigate the effect of training based on the health belief model and behavioral intention on dental and oral health behaviors in female students aged 9–12 years old in the city of Rudsar, Guilan, Iran.

Methods

This research is an interventional study conducted on 84 female students aged 9–12 years old, who lived in the city of Rudsar (n = 42 in the control group and n = 42 in the interventional group) in 2019. The data collection tools included questions on demographic variables, structures of the health belief model (perceived sensitivity, perceived severity, perceived barriers and benefits, self-efficiency), behavioral intention, and performance. The questionnaire was completed before the intervention and 3 months after it by both groups. The intervention group received four 45-min sessions. The data were analyzed using SPSS 24, descriptive tests, independent sample t-test, pair sample t-test, and regression (P < 0.05).

Results

The mean age of the intervention and control groups was 10.88 ± 1.01 and 10.80 ± 1.01, respectively. The results showed that the average scores of all structures of the health belief model and behavioral intention in the intervention group significantly changed compared to the average scores obtained before the intervention (P < 0.05). Moreover, the average scores of perceived sensitivity (p < 0.009), perceived barriers (p < 0.007), self-efficiency (p < 0.001), and behavioral intention (p < 0.001) significantly changed after the intervention in both groups (p < 0.05).

Conclusion

According to the results, the health belief model and the behavioral intention were effective in improving dental and oral health so that they can be applied to improving people's dental and oral health. It can also be used as a model to design, implement, and monitor medical health programs.
Knowledge, opinions and experiences of researchers regarding ethical regulation of biomedical research in Benin: a cross-sectional study
Authors: Gangbo Flore , Quenum Grâce , Guédou Fernand Aimé , Boko Martial
Published: November 2022

Background

Ethics in biomedical research is still a fairly new concept in Africa. This work aims to assess the knowledge, attitude and experiences of Beninese researchers with regard to the national ethical regulatory framework of biomedical research in Benin.

Methods

This was a cross-sectional and descriptive study, involving all the researchers fulfilling the inclusion criteria. Data were collected through a face-to-face interview using a questionnaire and analysed. Proportions and means were calculated with their confidence intervals and standard deviations, respectively.

Results

Of the 110 participants included in the study, 40.9% were medical lecturers and 71.1% had been involved in more than 10 biomedical research as researcher. Less than three quarters (69.1%) were able to correctly quote the basic principles from Belmont report. The quarter (25.45%) of them knew the attributions of the National Ethics Committee for Health Research (CNERS in French) and 38.2%, the content of the legislation on health research ethics in Benin. The common ethical rules were known by 69.1% of the participants. A quarter (25.5%) of participants said they always present the study’s briefing note to their study participants and 62.7% said they systematically request informed consent. For those who do not present the briefing note to participants, the main reasons provided were the researchers’ difficulties in writing the note in plain language and the participants’ limitation in understanding it.

Conclusions

The foundations of a good ethical framework for health research exist in Benin. However, the deployment and use of the various legal texts deserve to be improved.
Clinician perceptions of a clinical decision support system to reduce cardiovascular risk among prediabetes patients in a predominantly rural healthcare system
Authors: Saman Daniel M. , Allen Clayton I. , Freitag Laura A. , Harry Melissa L. , Sperl-Hillen JoAnn M. , Ziegenfuss Jeanette Y. , Haapala Jacob L. , Crain A. Lauren , Desai Jay R. , Ohnsorg Kris A. , O’Connor Patrick J.
Published: November 2022

Background

The early detection and management of uncontrolled cardiovascular risk factors among prediabetes patients can prevent cardiovascular disease (CVD). Prediabetes increases the risk of CVD, which is a leading cause of death in the United States. CVD clinical decision support (CDS) in primary care settings has the potential to reduce cardiovascular risk in patients with prediabetes while potentially saving clinicians time. The objective of this study is to understand primary care clinician (PCC) perceptions of a CDS system designed to reduce CVD risk in adults with prediabetes.

Methods

We administered pre-CDS implementation (6/30/2016 to 8/25/2016) (n = 183, 61% response rate) and post-CDS implementation (6/12/2019 to 8/7/2019) (n = 131, 44.5% response rate) independent cross-sectional electronic surveys to PCCs at 36 randomized primary care clinics participating in a federally funded study of a CVD risk reduction CDS tool. Surveys assessed PCC demographics, experiences in delivering prediabetes care, perceptions of CDS impact on shared decision making, perception of CDS impact on control of major CVD risk factors, and overall perceptions of the CDS tool when managing cardiovascular risk.

Results

We found few significant differences when comparing pre- and post-implementation responses across CDS intervention and usual care (UC) clinics. A majority of PCCs felt well-prepared to discuss CVD risk factor control with patients both pre- and post-implementation. About 73% of PCCs at CDS intervention clinics agreed that the CDS helped improve risk control, 68% reported the CDS added value to patient clinic visits, and 72% reported they would recommend use of this CDS system to colleagues. However, most PCCs disagreed that the CDS saves time talking about preventing diabetes or CVD, and most PCCs also did not find the clinical domains useful, nor did PCCs believe that the clinical domains were useful in getting patients to take action. Finally, only about 38% reported they were satisfied with the CDS.

Conclusions

These results improve our understanding of CDS user experience and can be used to guide iterative improvement of the CDS. While most PCCs agreed the CDS improves CVD and diabetes risk factor control, they were generally not satisfied with the CDS. Moreover, only 40–50% agreed that specific suggestions on clinical domains helped patients to take action. In spite of this, an overwhelming majority reported they would recommend the CDS to colleagues, pointing for the need to improve upon the current CDS.

Trial registration: NCT02759055 03/05/2016.
Prevalence of social risk factors and social needs in a Medicaid Accountable Care Organization (ACO)
Authors: Schiavoni Katherine H. , Helscel Kristy , Vogeli Christine , Thorndike Anne N. , Cash Rebecca E. , Camargo Carlos A. , Samuels-Kalow Margaret E.
Published: November 2022

Background

Health-related social needs (HRSN) are associated with higher chronic disease prevalence and healthcare utilization. Health systems increasingly screen for HRSN during routine care. In this study, we compare the differential prevalence of social risk factors and social needs in a Medicaid Accountable Care Organization (ACO) and identify the patient and practice characteristics associated with reporting social needs in a different domain from social risks.

Methods

Cross-sectional study of patient responses to HRSN screening February 2019-February 2020. HRSN screening occurred as part of routine primary care and assessed social risk factors in eight domains and social needs by requesting resources in these domains. Participants included adult and pediatric patients from 114 primary care practices. We measured patient-reported social risk factors and social needs from the HRSN screening, and performed multivariable regression to evaluate patient and practice characteristics associated with reporting social needs and concordance to social risks. Covariates included patient age, sex, race, ethnicity, language, and practice proportion of patients with Medicaid and/or Limited English Proficiency (LEP).

Results

Twenty-seven thousand four hundred thirteen individuals completed 30,703 screenings, including 15,205 (55.5%) caregivers of pediatric patients. Among completed screenings, 13,692 (44.6%) were positive for ≥ 1 social risk factor and 2,944 (9.6%) for ≥ 3 risks; 5,861 (19.1%) were positive for social needs and 4,848 (35.4%) for both. Notably, 1,013 (6.0%) were negative for social risks but positive for social needs. Patients who did not identify as non-Hispanic White or were in higher proportion LEP or Medicaid practices were more likely to report social needs, with or without social risks. Patients who were non-Hispanic Black, Hispanic, preferred non-English languages or were in higher LEP or Medicaid practices were more likely to report social needs without accompanying social risks.

Conclusions

Half of Medicaid ACO patients screened for HRSN reported social risk factors or social needs, with incomplete overlap between groups. Screening for both social risks and social needs can identify more individuals with HRSN and increase opportunities to mitigate negative health outcomes.
Criteria for the selection of complementary private health insurance: the experience of a large organisation in Iran
Authors: Bazyar Mohammad , Alipouri Sakha Minoo , Gordeev Vladimir Sergeevich , Mousavi Batool , Karmi Amir , Maniei Reza , Attari Saeed , Ranjbar Mohammad
Published: November 2022

Background

Expenses related to employee’s health benefit packages are rising. Hence, organisations are looking for complementary health financing arrangements to provide more financial protection for employees. This study aims to develop criteria to choose the most appropriate complementary health insurance company based on the experience of a large organisation in Iran.

Methods

This study was conducted in 2021 in Iran, in the Foundation of Martyrs and Veterans Affairs to find as many applicable criteria as possible. To develop a comprehensive list of criteria, we used triangulation in data sources, including review of relevant national and international documents, in-depth interviews of key informants, focus group discussion, and examining similar but unpublished checklists used by other organisations in Iran. The list of criteria was prioritised during focus group discussions. We used the best-worst method as a multi-criteria decision making method and a qualitative consensus among the key informants to value the importance of each of the finalised criteria.

Findings

Out of 85 criteria, we selected 28 criteria to choose an insurer for implementing complementary private health insurance. The finalised criteria were fell into six domains: (i) Previous experience of the applicants; (ii) Communication with clients; (iii) Financial status; (iv) Health care providers’ network; (v) Technical infrastructure and workforce; (vi) and Process of reviewing claims and reimbursement.

Conclusion

We propose a quantitative decision-making checklist to choose the best complimentary private health insurance provider. We invite colleagues to utilise, adapt, modify, or develop these criteria to suit their organisational needs. This checklist can be applied in any low- and middle-income country where the industry of complementary health insurance is blooming.
The burden of chronic obstructive pulmonary disease and its attributable risk factors in the Middle East and North Africa region, 1990–2019
Authors: Feizi Hamidreza , Alizadeh Mahasti , Nejadghaderi Seyed Aria , Noori Maryam , Sullman Mark J. M. , Ahmadian Heris Javad , Kolahi Ali-Asghar , Collins Gary S. , Safiri Saeid
Published: November 2022

Background

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease that is characterised by persistent respiratory symptoms and airflow limitation. The present study reported the burden of COPD, and its attributable risk factors, in the Middle East and North Africa (MENA) region between 1990 and 2019, by age, sex and socio-demographic index (SDI).

Methods

Data from the Global Burden of Disease (GBD) 2019 study were used to report the burden of COPD in the MENA countries. The prevalence, deaths, and disability-adjusted life-years (DALYs) were presented as counts and age-standardised rates per 100,000 population, with their associated 95% uncertainty intervals (UIs).

Results

In 2019, the regional age-standardised point prevalence and rates of death due to COPD were 2333.9 (2230.1, 2443.6) and 26.1 (22.2, 29.5) per 100,000, which represent a 30.6% (28.2%, 33.0%) increase and an 18.0% (2.8%, 30.9%) decrease, respectively, since 1990. The regional age-standardised DALY rate in 2019 was 649.1 (574.6, 717.7) per 100,000, which had decreased by 11.8% (0.9%, 21.1%) since 1990. Turkey had the highest age-standardised point prevalence in 2019 [3287.1 (3187.4, 3380.3)], while Afghanistan had the highest age-standardised death [40.4 (24.2, 52.6)] and DALY [964.5 (681.8, 1203.2)] rates. The regional age-standardised point prevalence, death and DALY rates in 2019 increased with advancing age and were higher in males in almost all age groups. There was a U-shaped association between SDI and the burden of COPD over the period 1990 to 2019. Moreover, in 2019 smoking (43.7%), ambient particulate matter pollution (22.8%) and occupational particulate matter (11.4%) had the largest proportion of attributable DALYs for both sexes.

Conclusions

COPD is one of the leading causes of death and disability in the MENA region, although the age-standardised burden has decreased over the last 30 years. Nevertheless, COPD accounted for a substantial number of deaths and DALYs, especially among the elderly. Programs targeting risk factors, like smoking, should be taken into consideration.
CircGSAP alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating miR-27a-3p/BMPR2 axis
Authors: Sun Yuanyuan , Jiang Rong , Hu Xiaoyi , Gong Sugang , Wang Lan , Wu Wenhui , Li Jinling , Kang Xinyang , Xia Shijin , Liu Jinming , Zhao Qinhua , Yuan Ping
Published: November 2022

Background

Our previous study showed that circular RNA-gamma-secretase-activating protein (circGSAP) was down-regulated in pulmonary microvascular endothelial cells (PMECs) in response to hypoxia, and regulated the cell cycle of PMECs via miR-942-5p sponge in pulmonary hypertension (PH). However, the mechanism whether circGSAP affects the dysfunction of PEMCs through other microRNAs (miRNAs) remains largely unknown. Therefore, we aimed to demonstrate the underlying mechanisms of circGSAP regulating PMECs dysfunction by absorbing other miRNAs to regulate target genes in idiopathic pulmonary arterial hypertension (IPAH).

Methods

Quantitative real-time polymerase chain reaction, immunofluorescence staining, Cell Counting Kit-8, Calcein-AM/PI staining, Transwell assay, dual-luciferase reporter assay, and ELISA were used to elucidate the roles of circGSAP.

Results

Here we showed that plasma circGSAP levels were significantly decreased in patients with IPAH and associated with poor outcomes. In vivo, circGSAP overexpression improved survival, and alleviated pulmonary vascular remodeling of monocrotaline-induced PH (MCT-PH) rats. In vitro, circGSAP overexpression inhibited hypoxia-induced PMECs proliferation, migration and increased mortality by absorbing miR-27a-3p. BMPR2 was identified as a miR-27a-3p target gene. BMPR2 silencing ameliorated the effect of the miR-27a-3p inhibitor on PMECs proliferation,migration and mortality. The levels of BMPR2 were upregulated in circGSAP-overexpressed PMECs and lung tissues of MCT-PH rats.

Conclusion

Our findings demonstrated that circGSAP alleviated the dysfunction of PMECs via the increase of BMPR2 by competitively binding with miR-27a-3p, and mitigated pulmonary vascular remodeling of MCT-PH rats, providing potential therapeutic strategies for IPAH.
Targeted blocking of CCR2 and CXCR2 improves the efficacy of transarterial chemoembolization of hepatocarcinoma
Authors: Tian Zhiqiang , Hou Xiaojuan , Liu Wenting , Shao Changchun , Gao Lu , Jiang Jinghua , Zhang Li , Han Zhipeng , Wei Lixin
Published: November 2022

Background

Transarterial chemoembolization (TACE) has been shown to prolong survival in patients with unresectable hepatocellular carcinoma (HCC); however, the long-term survival remains dismal. Targeting macrophage and neutrophil infiltration is a promising strategy. The CCL2/CCR2 and CXCLs/CXCR2 axes are required for recruitment of macrophages and neutrophils, respectively, in HCC. We investigated the feasibility of CCL2/CCR2 and CXCLs/CXCR2 as therapeutic targets in combination with TACE for treating HCC.

Methods

Expression of CCL2/CCR2 and CXCLs/CXCR2 was analyzed in the primary rat HCC model and one HCC cohort. The relationship between expression levels, neutrophil and macrophage infiltration, hepatocarcinogenesis progression in the rat model, and survival of HCC patients was assessed. The anti-tumor effects of blocking the CCL2/CCR2 and CXCLs/CXCR2 axes by CCR2 and CXCR2 antagonists in combination with TACE were evaluated in HCC rats. The numbers of macrophages, neutrophils, and hepatic progenitor cells were further determined to explore the underlying mechanisms.

Results

High macrophage and neutrophil infiltration and CXCL8 expression were associated with poor prognosis in the TCGA liver cancer dataset. High expression of CCL2/CCR2 and CXCL8/CXCR2 in clinical HCC specimens was associated with reduced survival. Expression of CCL2/CCR2 and CXCL1/CXCR2 was correlated with hepatocarcinogenesis progression in the primary rat HCC model. Blockade of CCL2/CCR2 and CXCLs/CXCR2 enhanced the anti-tumor effect of TACE treatment in this model. Blocking the CCL2/CCR2 and CXCLs/CXCR2 axes with CCR2 and CXCR2 antagonists in TACE-treated rats reduced macrophage and neutrophil infiltration and hepatic progenitor cell activation and thus overcame TACE resistance in HCC.

Conclusions

The results demonstrate the translational potential of immunotherapy targeting the CCL2/CCR2 and CXCLs/CXCR2 axes in combination with TACE therapy for the treatment of HCC.
Lactic acid modified rare earth-based nanomaterials for enhanced radiation therapy by disturbing the glycolysis
Authors: Liu Hu , Wang Han , Ni Dalong , Xu Youjia
Published: November 2022

Deficient deposition of X-rays and strong capacity of repairing damage DNA of cancer cells limit the effect of radiation therapy (RT). Herein, we synthesize CsLu2F7 nanoparticles with lactic acid (LA) ligands (CsLu2F7-LA) to overcome these limitations. The high-Z atoms of Lu and Cs can deposit more X-rays for generating enhanced hydroxyl radicals (·OH). Meanwhile, the LA ligand will guide CsLu2F7-LA to target monocarboxylic acid transporter (MCT) and impede the transportation of free LA, leading to decreased glycolysis and DNA damage repair. Consequently, the curative effect of RT will be enhanced and the strategy of LA accumulation induced radiosensitization is proved by in vivo and in vitro experiments, which will bring prospects for enhanced RT with nanomedicine.
Convergent validity of EQ-5D with core outcomes in dementia: a systematic review
Authors: Hussain Hannah , Keetharuth Anju , Rowen Donna , Wailoo Allan
Published: November 2022

Objectives

To explore through a systematic review, the convergent validity of EQ-5D (EQ-5D-3L and EQ-5D-5L (total score and dimensions)) with core outcomes in dementia and investigate how this may be impacted by rater-type; with the aim of informing researchers when choosing measures to use in dementia trials.

Methods

To identify articles relevant to the convergent validity of EQ-5D with core dementia outcomes, three databases were electronically searched to September 2022. Studies were considered eligible for inclusion within the review if they included individual level data from people with dementia of any type, collected self and/or proxy reported EQ-5D and collected at least one core dementia outcome measure. Relevant data such as study sample size, stage of dementia and administration of EQ-5D was extracted, and a narrative synthesis was adopted.

Results

The search strategy retrieved 271 unique records, of which 30 met the inclusion criteria for the review. Twelve different core outcome measures were used to capture dementia outcomes: cognition, function, and behaviour/mood across the studies. Most studies used EQ-5D-3L (n = 27). Evidence related to the relationship between EQ-5D and measures of function and behaviour/mood was the most robust, with unanimous directions of associations, and more statistically significant findings. EQ-5D dimensions exhibited associations with corresponding clinical outcomes, whereby relationships were stronger with proxy-EQ-5D (than self-report).

Conclusion

Measuring health-rated quality of life in dementia populations is a complex issue, particularly when considering balancing the challenges associated with both self and proxy report. Published evidence indicates that EQ-5D shows evidence of convergent validity with the key dementia outcomes, therefore capturing these relevant dementia outcomes. The degree of associations with clinical measures was stronger when considering proxy-reported EQ-5D and differed by EQ-5D dimension type. This review has revealed that, despite the limited targeted psychometric evidence pool and reliance on clinical and observational studies, EQ-5D exhibits convergent validity with other dementia outcome measures.
Job strain and burnout in Spanish nurses during the COVID-19: resilience as a protective factor in a cross-sectional study
Authors: Molero Jurado María del Mar , Martos Martínez África , Pérez-Fuentes María del Carmen , Castiñeira López Héctor , Gázquez Linares José Jesús
Published: November 2022

Background

Nurses are frequently exposed to chronic stress in the workplace generating harmful effects such as job strain and burnout. On the contrary, resilience has been shown to be a beneficial variable. The objective of this study was to analyze the relationship between dimensions of the Job Demand Control-Support model, resilience and burnout in nurses, and examine the mediating role of resilience between job strain and burnout.

Methods

A descriptive, cross-sectional study reported in line with the STROBE guidelines. Active nurses were invited to complete an online questionnaire in September, 2020. With snowball sampling, 1013 nurses, with a mean age of 34.71, filled out the Job Content Questionnaire, the Maslach Burnout Inventory and the Resilience Scale.

Results

The results showed the existence of four groups of professionals based on job strain. The nurses in the “High Strain” group (high demands and low control) showed higher scores in emotional exhaustion and cynicism, while those in the “Active Job” group scored higher in personal realization and resilience. The findings showed that job strain affects burnout in nurses, and this effect is mediated by resilience.

Conclusions

The findings of this study showed that a high level of resilience could exert a fundamental role in ensuring well-being and proper job performance by nurses. Nursing managers should see to the personable variables or competencies that provide and favor an opportunity for nurses to widen and improve their practice, in pursuance of satisfying and responding better to people’s needs and the systems they work for.
Neuronal nuclear calcium signaling suppression of microglial reactivity is mediated by osteoprotegerin after traumatic brain injury
Authors: Fröhlich Albrecht , Olde Heuvel Florian , Rehman Rida , Krishnamurthy Sruthi Sankari , Li Shun , Li Zhenghui , Bayer David , Conquest Alison , Hagenston Anna M. , Ludolph Albert , Huber-Lang Markus , Boeckers Tobias , Knöll Bernd , Morganti-Kossmann Maria Cristina , Bading Hilmar , Roselli Francesco
Published: November 2022

Background

Traumatic brain injury (TBI) is characterized by massive changes in neuronal excitation, from acute excitotoxicity to chronic hyper- or hypoexcitability. Nuclear calcium signaling pathways are involved in translating changes in synaptic inputs and neuronal activity into discrete transcriptional programs which not only affect neuronal survival and synaptic integrity, but also the crosstalk between neurons and glial cells. Here, we report the effects of blunting neuronal nuclear calcium signals in the context of TBI.

Methods

We used AAV vectors to express the genetically encoded and nuclear-targeted calcium buffer parvalbumin (PV.NLS.mCherry) or the calcium/calmodulin buffer CaMBP4.mCherry in neurons only. Upon TBI, the extent of neuroinflammation, neuronal death and synaptic loss were assessed by immunohistochemistry and targeted transcriptome analysis. Modulation of the overall level of neuronal activity was achieved by PSAM/PSEM chemogenetics targeted to parvalbumin interneurons. The functional impact of neuronal nuclear calcium buffering in TBI was assessed by quantification of spontaneous whisking.

Results

Buffering neuronal nuclear calcium unexpectedly resulted in a massive and long-lasting increase in the recruitment of reactive microglia to the injury site, which was characterized by a disease-associated and phagocytic phenotype. This effect was accompanied by a substantial surge in synaptic loss and significantly reduced whisking activity. Transcriptome analysis revealed a complex effect of TBI in the context of neuronal nuclear calcium buffering, with upregulation of complement factors, chemokines and interferon-response genes, as well as the downregulation of synaptic genes and epigenetic regulators compared to control conditions. Notably, nuclear calcium buffering led to a substantial loss in neuronal osteoprotegerin (OPG), whereas stimulation of neuronal firing induced OPG expression. Viral re-expression of OPG resulted in decreased microglial recruitment and synaptic loss. OPG upregulation was also observed in the CSF of human TBI patients, underscoring its translational value.

Conclusion

Neuronal nuclear calcium signals regulate the degree of microglial recruitment and reactivity upon TBI via, among others, osteoprotegerin signals. Our findings support a model whereby neuronal activity altered after TBI exerts a powerful impact on the neuroinflammatory cascade, which in turn contributes to the overall loss of synapses and functional impairment.
The role of the ZEB1–neuroinflammation axis in CNS disorders
Authors: Poonaki Elham , Kahlert Ulf Dietrich , Meuth Sven G. , Gorji Ali
Published: November 2022

Zinc finger E-box binding homeobox 1 (ZEB1) is a master modulator of the epithelial–mesenchymal transition (EMT), a process whereby epithelial cells undergo a series of molecular changes and express certain characteristics of mesenchymal cells. ZEB1, in association with other EMT transcription factors, promotes neuroinflammation through changes in the production of inflammatory mediators, the morphology and function of immune cells, and multiple signaling pathways that mediate the inflammatory response. The ZEB1–neuroinflammation axis plays a pivotal role in the pathogenesis of different CNS disorders, such as brain tumors, multiple sclerosis, cerebrovascular diseases, and neuropathic pain, by promoting tumor cell proliferation and invasiveness, formation of the hostile inflammatory micromilieu surrounding neuronal tissues, dysfunction of microglia and astrocytes, impairment of angiogenesis, and dysfunction of the blood–brain barrier. Future studies are needed to elucidate whether the ZEB1–neuroinflammation axis could serve as a diagnostic, prognostic, and/or therapeutic target for CNS disorders.
Neuroimmune proteins can differentiate between tauopathies
Authors: Cherry Jonathan D. , Baucom Zach H. , Eppich Kaleb G. , Kirsch Daniel , Dixon Erin R. , Tripodis Yorghos , Bieniek Kevin F. , Farrell Kurt , Whitney Kristen , Uretsky Madeline , Crary John F. , Dickson Dennis , McKee Ann C.
Published: November 2022

Background

Tauopathies are a group of neurodegenerative diseases where there is pathologic accumulation of hyperphosphorylated tau protein (ptau). The most common tauopathy is Alzheimer’s disease (AD), but chronic traumatic encephalopathy (CTE), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and argyrophilic grain disease (AGD) are significant health risks as well. Currently, it is unclear what specific molecular factors might drive each distinct disease and represent therapeutic targets. Additionally, there is a lack of biomarkers that can differentiate each disease in life. Recent work has suggested that neuroinflammatory changes might be specific among distinct diseases and offers a novel resource for mechanistic targets and biomarker candidates.

Methods

To better examine each tauopathy, a 71 immune-related protein multiplex ELISA panel was utilized to analyze anterior cingulate grey matter from 127 individuals neuropathologically diagnosed with AD, CTE, PSP, CBD, and AGD. A partial least square regression analysis was carried out to perform unbiased clustering and identify proteins that are distinctly correlated with each tauopathy correcting for age and gender. Receiver operator characteristic and binary logistic regression analyses were then used to examine the ability of each candidate protein to distinguish diseases. Validation in postmortem cerebrospinal fluid (CSF) from 15 AD and 14 CTE cases was performed to determine if candidate proteins could act as possible novel biomarkers.

Results

Five clusters of immune proteins were identified and compared to each tauopathy to determine if clusters were specific to distinct disease. Each cluster was found to correlate with either CTE, AD, PSP, CBD, or AGD. When examining which proteins were the strongest driver of each cluster, it was observed the most distinctive protein for CTE was CCL21, AD was FLT3L, and PSP was IL13. Individual proteins that were specific to CBD and AGD were not observed. CCL21 was observed to be elevated in CTE CSF compared to AD cases (p = 0.02), further validating the use as possible biomarkers. Sub-analyses for male only cases confirmed the results were not skewed by gender differences.

Conclusions

Overall, these results highlight that different neuroinflammatory responses might underlie unique mechanisms in related neurodegenerative pathologies. Additionally, the use of distinct neuroinflammatory signatures could help differentiate between tauopathies and act as novel biomarker candidate to increase specificity for in-life diagnoses.