bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of previous infection with SARS-CoV-2 in protecting against omicron reinfections and severe complications of COVID-19 compared to pre-omicron variants: a systematic review
Authors: Arabi Maryam , Al-Najjar Yousef , Sharma Omna , Kamal Ibtihal , Javed Aimen , Gohil Harsh S. , Paul Pradipta , Al-Khalifa Aljazi M. , Laws Sa’ad , Zakaria Dalia
Published: June 2023

Background

The SARS-CoV-2 virus elicited a major public concern worldwide since December 2019 due to the high number of infections and deaths caused by COVID-19. The Omicron variant was detected in October 2021 which evolved from the wild-type SARS-CoV-2 and was found to possess many mutations. Omicron exhibited high transmissibility and immune evasion as well as reduced severity when compared to the earlier variants. Although vaccinated individuals were largely protected against infections in previous waves, the high prevalence of both reinfections and breakthrough infections with Omicron was observed. The aim of this review is to understand the effectiveness of previous infection on subsequent reinfection, given its significance in driving public health policy, including vaccination prioritization and lockdown requirements.

Methods

A comprehensive literature search was conducted using several databases to target studies reporting data related to the effectiveness of the previous infection with SARS-CoV-2 in protecting against the Omicron variant. Screening of the studies, quality assessment and data extraction were conducted by two reviewers for each study.

Results

Only 27 studies met our inclusion criteria. It was observed that previous infection was less effective in preventing reinfections with the Omicron variant compared to the Delta variant irrespective of vaccination status. Furthermore, being fully vaccinated with a booster dose provided additional protection from the Omicron variant. Additionally, most infections caused by Omicron were asymptomatic or mild and rarely resulted in hospitalizations or death in comparison to the Delta wave.

Conclusion

A majority of the studies reached a consensus that although previous infection provides some degree of immunity against Omicron reinfection, it is much lower in comparison to Delta. Full vaccination with two doses was more protective against Delta than Omicron. Receiving a booster dose provided additional protection against Omicron. It is therefore clear that neither vaccination nor previous infection alone provide optimal protection; hybrid immunity has shown the best results in terms of protecting against either Omicron or Delta variants. However, additional research is needed to quantify how long immunity from vaccination versus previous infection lasts and whether individuals will benefit from variant-specific vaccinations to enhance protection from infection.
Decision-analytic evaluation of the comparative effectiveness and cost-effectiveness of strategies to prevent breast and ovarian cancer in German women with BRCA-1/2 mutations
Authors: Hallsson Lára R. , Sroczynski Gaby , Engel Jutta , Siebert Uwe
Published: June 2023

Background

Women with inherited mutations in the BRCA1 or BRCA2 genes have increased lifetime risks for developing breast and/or ovarian cancer and may develop these cancers around the age of 30 years. Therefore, prevention of breast and ovarian cancer in these women may need to start relatively early in life. In this study we systematically evaluate the long-term effectiveness and cost effectiveness of different prevention strategies for breast and ovarian cancer in women with BRCA-1/2 mutation in Germany.

Methods

A decision-analytic Markov model simulating lifetime breast and ovarian cancer development in BRCA-1/2 carriers was developed. Different strategies including intensified surveillance (IS), prophylactic bilateral mastectomy (PBM), and prophylactic bilateral salpingo-oophorectomy (PBSO) alone or in combination at different ages were evaluated. German clinical, epidemiological, and economic (in 2022 Euro) data were used. Outcomes included cancer incidences, mortality, life years (LYs), quality-adjusted life years (QALYs), and discounted incremental cost-effectiveness ratios (ICER). We adopted the German health-care system perspective and discounted costs and health effects with 3% annually.

Results

All intervention strategies are more effective and less costly than IS alone. Prevention with PBM plus PBSO at age 30 maximizes life expectancy with 6.3 LYs gained, whereas PBM at age 30 with delayed PBSO at age 35 improves quality of life with 11.1 QALYs gained, when compared to IS alone. A further delay of PBSO was associated with lower effectiveness. Both strategies are cost effective with ICERs significantly below 10,000 EUR/LYG or QALY.

Conclusion

Based on our results, PBM at age 30 plus PBSO between age 30 and 40 prolongs life and is cost effective in women with BRCA-1/2 mutations in Germany. Serial preventive surgeries with delayed PBSO potentially improve quality of life for women. However, delaying PBM and/or PBSO further may lead to increased mortality and reduced QALYs.
Time to recovery from severe acute malnutrition and its predictors among under five children admitted to therapeutic feeding units of general and referral hospitals in Tigray, Ethiopia, 2020: a prospective cohort study
Authors: Kidane Gebretsadkan Fisseha , Zereabruk Kidane , Aberhe Woldu , Hailay Abrha , Mebrahtom Guesh , Gebremeskel Gebreamlak Gebremedhn , Haile Teklehaimanot Gereziher , Teklemichael Desalegn Massa
Published: June 2023

Background

Across the globe, an estimated 16 million children under the age of 5 are affected by severe acute malnutrition. Children with severe acute malnutrition are nine times more likely to die than well-nourished children. In Ethiopia, 7% of children under five are wasted, and 1% of these are severely wasted. A prolonged hospital stay increases the incidence of hospital-acquired infections. The aim of this study was to assess the time to recovery and its predictors among children 6–59 months old with severe acute malnutrition admitted to therapeutic feeding units of selected general and referral hospitals in Tigray, Ethiopia.

Methods

A prospective cohort study design was conducted among children aged 6–59 months admitted with severe acute malnutrition in selected hospitals in Tigray that have therapeutic feeding units. The data were cleaned, coded, entered into Epi-data Manager, and exported to STATA 14 for analysis.

Result

Among 232 children followed in the study, 176 have recovered from severe acute malnutrition with a recovery rate of 54 per 1000 person-days observation and the median time to recovery was 16 days with an inter-quartile range of 8. In a multivariable Cox Regression, feeding plumpy nut [AHR 0.49 (95% CI 0.2717216-0.8893736)] and failing to gain 5 gr/kg/day for three successive days after feeding freely on F-100 [AHR 3.58 (95% CI 1.78837–7.160047)] were found to have an association with time to recovery.

Conclusion

Despite the median time to recovery is shorter than what has been reported in a few studies, we can conclude that this could not let children avoid any possible hospital-acquired infections. The impact of staying in a hospital may also extend to the mother/caregiver in terms of the infection that they may acquire or the costs imposed on them.
Modeling potential risk areas of Orthohantavirus transmission in Northwestern Argentina using an ecological niche approach
Authors: López Walter R. , Altamiranda-Saavedra Mariano , Kehl Sebastián D. , Ferro Ignacio , Bellomo Carla , Martínez Valeria P. , Simoy Mario I. , Gil José F.
Published: June 2023

Background

Hantavirus Pulmonary Syndrome (HPS) is a rodent-borne zoonosis in the Americas, with up to 50% mortality rates. In Argentina, the Northwestern endemic area presents half of the annually notified HPS cases in the country, transmitted by at least three rodent species recognized as reservoirs of Orthohantavirus. The potential distribution of reservoir species based on ecological niche models (ENM) can be a useful tool to establish risk areas for zoonotic diseases. Our main aim was to generate an Orthohantavirus risk transmission map based on ENM of the reservoir species in northwest Argentina (NWA), to compare this map with the distribution of HPS cases; and to explore the possible effect of climatic and environmental variables on the spatial variation of the infection risk.

Methods

Using the reservoir geographic occurrence data, climatic/environmental variables, and the maximum entropy method, we created models of potential geographic distribution for each reservoir in NWA. We explored the overlap of the HPS cases with the reservoir-based risk map and a deforestation map. Then, we calculated the human population at risk using a census radius layer and a comparison of the environmental variables’ latitudinal variation with the distribution of HPS risk.

Results

We obtained a single best model for each reservoir. The temperature, rainfall, and vegetation cover contributed the most to the models. In total, 945 HPS cases were recorded, of which 97,85% were in the highest risk areas. We estimated that 18% of the NWA population was at risk and 78% of the cases occurred less than 10 km from deforestation. The highest niche overlap was between Calomys fecundus and Oligoryzomys chacoensis.

Conclusions

This study identifies potential risk areas for HPS transmission based on climatic and environmental factors that determine the distribution of the reservoirs and Orthohantavirus transmission in NWA. This can be used by public health authorities as a tool to generate preventive and control measures for HPS in NWA.
Influence of education and subjective financial status on dietary habits among young, middle-aged, and older adults in Japan: a cross-sectional study
Authors: Nishinakagawa Maki , Sakurai Ryota , Nemoto Yuta , Matsunaga Hiroko , Takebayashi Toru , Fujiwara Yoshinori
Published: June 2023

Background

Research has suggested an association between lower socioeconomic status (SES) and unhealthy dietary habits. However, differences in the effects of different SES indicators and age remain unclear. The current study addressed this research gap by investigating the relationship between SES and unhealthy dietary habits, specifically focusing on educational attainment and subjective financial status (SFS) among varied age groups.

Methods

Data were derived from a mail survey of 8,464 people living in a suburb of Tokyo, Japan. Participants were classified into three age groups (20–39 years: young adults; 40–64 years: middle-aged adults; and 65–97 years: older adults). SES was assessed based on individual educational attainment and SFS. Unhealthy dietary habits were defined as skipping breakfast and a low frequency of balanced meal consumption. Participants were asked how often they ate breakfast, and those who did not respond “every day” were categorized as “breakfast skippers.” Low frequency of balanced meal consumption was defined as eating a meal that included a staple meal, main dish, and side dishes at least twice a day for less than five days per week. Poisson regression analyses with robust variance adjusted for potential covariates were used to determine the interactive effects of educational attainment and SFS on unhealthy dietary habits.

Results

Individuals with lower educational attainment across all age groups skipped breakfast more frequently compared to those with higher educational attainment. For older adults, poor SFS was associated with skipping breakfast. Young adults with poor SFS and middle-aged adults with lower educational attainment tended to eat less balanced meals. In addition, an interaction effect was found in older adults, where those with lower education despite good SFS and those with poor SFS despite higher education were at a greater risk of falling into unhealthy diet.

Conclusions

The findings suggested that different SES indicators affect healthy dietary habits in different generations, and therefore, health policies should consider the potential influence of different SES on promoting healthier dietary habits.
Impact on sales of adding a smaller serving size of beer and cider in licensed premises: an A-B-A reversal design
Authors: Mantzari Eleni , Ventsel Minna , Pechey Emily , Lee Ilse , Pilling Mark , Hollands Gareth J. , Marteau Theresa M.
Published: June 2023

Background

Smaller serving sizes of alcoholic drinks could reduce alcohol consumption across populations thereby lowering the risk of many diseases. The effect of modifying the available range of serving sizes of beer and cider in a real-world setting has yet to be studied. The current study assessed the impact on beer and cider sales of adding a serving size of draught beer and cider (2/3 pint) that was between the current smallest (1/2 pint) and largest (1 pint) standard serving sizes.

Methods

Twenty-two licensed premises in England consented to taking part in the study. The study used an ABA reversal design, set over three 4-weekly periods, with A representing the non-intervention periods, during which standard serving sizes were served and B the intervention period when a 2/3 pint serving size of draught beer and cider was added to the existing range, along with smaller 1/2 pint and larger 1 pint serving sizes. The primary outcome was the daily volume of beer and cider sold, extracted from sales data.

Results

Fourteen premises started the study, of which thirteen completed it. Twelve of those did soper protocoland were included in the primary analysis. After adjusting for pre-specified covariates, the intervention did not have a significant effect on the volume of beer and cider sold per day (3.14 ml; 95%CIs -2.29 to 8.58;p = 0.257).

Conclusions

In licensed premises, there was no evidence that adding a smaller serving size for draught beer and cider (2/3 pint) when the smallest (1/2 pint) and largest (1 pint) sizes were still available, affected the volume of beer and cider sold. Studies are warranted to assess the impact of removing the largest serving size.

Trial registration

ISRCTN:https://doi.org/10.1186/ISRCTN33169631(08/09/2021), OSF:https://osf.io/xkgdb/(08/09/2021).
Pneumothorax detection with thoracic ultrasound as the method of choice in interventional pulmonology - A retrospective single-center analysis and experience
Authors: Sieber Sonja , Garbe Jakob , Böhm Sebastian , Eisenmann Stephan
Published: June 2023

Background

Recent studies have shown that thoracic ultrasound (TUS) is not inferior to chest radiography (CR) in detecting pneumothorax (PTX). It is unclear if adopting TUS can reduce the number of CR in the daily clinical routine. This retrospective study investigates the utilization of post-interventional CR and TUS for PTX detection after the introduction of TUS as the method of choice in an interventional pulmonology unit.

Methods

All interventions with CR or TUS for ruling out PTX performed in the Pneumology Department of the University Hospital Halle (Germany) 2014 to 2020 were included. The documented TUS and CR performed before (period A) and after the introduction of TUS as the method of choice (period B), as well as the number of diagnosed and missed PTX were recorded.

Results

The study included 754 interventions (110 in period A and 644 in period B). The proportion of CR decreased from 98.2% (n = 108) to 25.8% (n = 166) (p < 0.001). During period B, a total of 29 (4.5%) PTX were diagnosed. Of these, 28 (96.6%) were detected on initial imaging (14 by CR, 14 by TUS ). One PTX (0.2%) was initially missed by TUS, none by CR. Confirmatory investigations were ordered more frequently after TUS (21 of 478, 4.4%) than after CR (3 of 166, 1.8%).

Conclusion

The use of TUS in interventional pulmonology can effectively reduce the number of CR and thus save resources. However, CR may still be favored in specific circumstances or if pre-existing conditions limit sonographic findings.
Effects of G-CSF on hPDLSC proliferation and osteogenic differentiation in the LPS-induced inflammatory microenvironment
Authors: Yu Hui , Wang Pengcheng , Lu Haibin , Guan Jiurong , Yao Fang , Zhang Tianyi , Wang Qiuxu , Wang Zuomin
Published: June 2023

Background

Periodontitis is a chronic infectious disease of periodontal support tissue caused by microorganisms in dental plaque, which causes alveolar bone resorption and tooth loss. Periodontitis treatment goals include prevention of alveolar bone resorption and promotion of periodontal regeneration. We previously found that granulocyte colony-stimulating factor (G-CSF) was involved in periodontitis-related alveolar bone resorption through induction of an immune response and subsequent destruction of periodontal tissue. However, the mechanisms underlying the effects of G-CSF on abnormal bone remodeling have not yet been fully elucidated. Human periodontal ligament stem cells (hPDLSCs) are major modulators of osteogenic differentiation in periodontal tissues. Thus, the aim of this study was to investigated whether G-CSF acts effects on hPDLSC proliferation and osteogenic differentiation, as well as periodontal tissue repair.

Methods

hPDLSCs were cultured and identified by short tandem repeat analysis. The expression patterns and locations of G-CSF receptor (G-CSFR) on hPDLSCs were detected by immunofluorescence analysis. The effects of G-CSF on hPDLSCs in a lipopolysaccharide (LPS)-induced inflammatory microenvironment were investigated. Specifically, Cell-Counting Kit 8 (CCK8) and Alizarin red staining were used to examine hPDLSC proliferation and osteogenic differentiation; reverse transcription-polymerase chain reaction was performed to detect the expression patterns of osteogenesis-related genes (alkaline phosphatase [ALP], runt-related transcription factor 2 [Runx2], and osteocalcin [OCN]) in hPDLSCs; and Western blotting was used to detect the expression patterns of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) of PI3K/Akt signaling pathway.

Results

hPDLSCs exhibited a typical spindle-shaped morphology and good clonogenic ability. G-CSFR was mostly localized on the cell surface membrane. Analyses showed that G-CSF inhibited hPDLSC proliferation. Also, in the LPS-induced inflammatory microenvironment, G-CSF inhibited hPDLSC osteogenic differentiation and reduced the expression levels of osteogenesis-related genes. G-CSF increased the protein expression levels of hPDLSC pathway components p-PI3K and p-Akt.

Conclusions

We found that G-CSFR was expressed on hPDLSCs. Furthermore, G-CSF inhibited hPDLSC osteogenic differentiation in vitro in the LPS-induced inflammatory microenvironment.
The gap between bachelor’s degree graduates in health informatics and employer needs in Saudi Arabia
Authors: Alzghaibi Haitham
Published: June 2023

Background

In the field of health informatics (HI), there is a crucial gap between employers’ needs and the output of academic programmes. Although industrial organisations and government agencies recognise the importance of training and education in the development and operation of health-information systems, advancements in educational programmes have been comparatively slow in terms of investment in healthcare information technology. This study aims to determine the gap between employer demands and academic programmes in HI in Saudi Arabia.

Methods

This mixed-methods study collected both qualitative and quantitative data. A qualitative content analysis was performed to identify the role of advertised HI jobs using two sources: Google and LinkedIn. In addition, university websites were searched to determine job opportunities for graduates with a bachelor’s degree in HI. Next, a quantitative, cross-sectional self-report questionnaire was administered to validate the findings of the qualitative data. Data obtained were analysed using SPSS, N-Vivo, and Microsoft Excel.

Results

The study’s data were obtained from four sources: Google search engine, LinkedIn, five Saudi university websites, and 127 HI experts. The results show a discrepancy between academic programmes’ outputs and employer recruitment needs. In addition, the results reveal a preference for post-graduate degrees, either a master’s or PhD degree, with a bachelor’s degree in a health or medical discipline.

Conclusions

Employers tend to prefer applicants with a bachelor’s degree in computer science or information technology over those with a degree in HI. Academic programmes should incorporate more practical applications and provide students with a thorough understanding of the healthcare industry to better equip them as efficient future HI professionals.
The impact of global health outreach experiences on medical student burnout
Authors: Kuehn Thomas , Crandall Cody , Schmidt Jefferson , Richards Zeke , Park Taylor , Szczepaniak Morgan , Zapata Isain , Wardle Mark
Published: June 2023

Background

Student burnout during medical education is a prevalent and critical problem. Burnout has reaching consequences, including negative health outcomes for students, financial loss for schools, and worsened patient care as students transition to practice. Global Health Outreach Experiences (GHOEs), known to enhance cultural awareness and clinical knowledge among medical students, are offered in most programs. Prior studies document that GHOEs benefit physicians suffering from burnout, with effects demonstrating improvement over 6 months. No study, to our knowledge, has assessed the influence GHOEs may have on medical student burnout with a comparable control group. This study examines whether participation in a GHOE, compared to a standard break from school, has a positive effect on burnout.

Methods

A case control study utilizing the Copenhagen Burnout Inventory was conducted on medical students. 41 students participated in a one-week, spring break GHOE and 252 were randomly selected as non-participating students in a control group. Assessments were gathered 1 week prior, 1 week after, and 10 weeks after spring break. Response across the surveys in chronological order included 22, 20, 19 GHOE and 70, 66, 50 control participants.

Results

A significant reduction in personal burnout (PB) (P = 0.0161), studies related burnout (SRB) (P = 0.0056), and colleagues related burnout (CRB) (P = 0.0357) was found among GHOE attendees compared to control participants at 10-weeks after spring break. When modeled with potential confounders, CRB and SRB reductions remained significant.

Conclusion

GHOEs may be a potential tool for institutions to combat burnout rates in their students. The benefits of GHOEs appear to enhance over time.
An exploratory university-based cross-sectional study of the prevalence and reporting of mistreatment and student-related factors among Thai medical students
Authors: Naothavorn Waravudh , Puranitee Pongtong , Kaewpila Winitra , Sumrithe Sutida , Heeneman Sylvia , van Mook Walther N. K. A. , Busari Jamiu O.
Published: June 2023

Background

Mistreatment is a behavior that reflects disrespect for the dignity of others. Mistreatment can be intentional or unintentional, and can interfere with the process of learning and perceived well-being. This study explored the prevalence and characteristics of mistreatment, mistreatment reporting, student-related factors, and consequences among medical students in Thai context.

Methods

We first developed a Thai version of the Clinical Workplace Learning Negative Acts Questionnaire-Revised (NAQ-R) using a forward-back translation process with quality analysis. The design was a cross-sectional survey study, using the Thai Clinical Workplace Learning NAQ-R, Thai Maslach Burnout Inventory-Student Survey, Thai Patient Health Questionnaire (to assess depression risk), demographic information, mistreatment characteristics, mistreatment reports, related factors, and consequences. Descriptive and correlational analyses using multivariate analysis of variance were conducted.

Results

In total, 681 medical students (52.4% female, 54.6% in the clinical years) completed the surveys (79.1% response rate). The reliability of the Thai Clinical Workplace Learning NAQ-R was high (Cronbach’s alpha 0.922), with a high degree of agreement (83.9%). Most participants (n = 510, 74.5%) reported that they had experienced mistreatment. The most common type of mistreatment was workplace learning-related bullying (67.7%), and the most common source was attending staff or teachers (31.6%). People who mistreated preclinical medical students were most often senior students or peers (25.9%). People who mistreated clinical students were most commonly attending staff (57.5%). Only 56 students (8.2%) reported these instances of mistreatment to others. Students’ academic year was significantly related to workplace learning-related bullying (r = 0.261, p < 0.001). Depression and burnout risk were significantly associated with person-related bullying (depression: r = 0.20, p < 0.001, burnout: r = 0.20, p = 0.012). Students who experienced person-related bullying were more often the subject of filed unprofessional behavior reports, concerning conflict or arguments with colleagues, being absent from class or work without reasonable cause, and mistreatment of others.

Conclusions

Mistreatment of medical students was evident in medical school and was related to the risk for depression and burnout, as well as the risk of unprofessional behavior.

Trial registration

TCTR20230107006(07/01/2023).
Socioeconomic factors, perceived stress, and social support effect on neonatal nurse burnout in China: a cross-sectional study
Authors: Huang Zhen-peng , Huang Fang , Liang Qun , Liao Feng-zhen , Tang Chuan-zhuang , Luo Min-lan , Lu Si-lan , Lian Jing-jing , Li Shan-e , Wei Su-qiao , Wu Bin
Published: June 2023

Background

Neonatal nurses’ working environments are highly stressful, and burnout is common. This study examines the effect of socioeconomic factors, perceived stress, and social support on neonatal nurse burnout.

Methods

A total of 311 neonatal nurses participated in this study. They were administered a validated Maslach Burnout Inventory. The study employed a 14-item perceived stress scale (PSS-14) and a social support rate scale (SSRS) to examine stress, socioeconomic factors, and lifestyles.

Results

Of the neonatal nurses, 40.19% had burnout, 89.60% had mild burnout, and 10.40% had moderate burnout; no neonatal nurse experienced severe burnout. Young nurses and those with low technical skills, poor interpersonal relationships, irregular diet, and insufficient rest were exposed to burnout (all p < 0.05).Most burnout nurses experienced moderate-severe perceived stress, and their PSS-14 scores were higher (all p < 0.05).The scores for objective social support, subjective social support, utilization of social support, total SSRS scores, and the level of social support were all lower in burnout nurses (all p < 0.05). Perceived stress was correlated positively and significantly with emotional exhaustion and personal accomplishment (all p < 0.05). Social support correlated significantly with and reduced personal accomplishments (p < 0.05). Age, poor interpersonal relationships, perceived stress, and social support were all independent factors associated with neonatal nurse burnout (all p < 0.05).

Conclusion

The prevalence of burnout in neonatal nurses was higher than average. Socioeconomic factors, higher perceived stress, and lower social support contribute to neonatal nurse burnout. Nursing managers should pay attention to socioeconomic factors, perceived stress, and social support among neonatal nurses and employ strategies to reduce neonatal nurse burnout.
Understanding the age spectrum of respiratory syncytial virus associated hospitalisation and mortality burden based on statistical modelling methods: a systematic analysis
Authors: Cong Bingbing , Dighero Izzie , Zhang Tiantian , Chung Alexandria , Nair Harish , Li You
Published: June 2023

Background

Statistical modelling studies based on excess morbidity and mortality are important for understanding RSV disease burden for age groups that are less frequently tested for RSV. We aimed to understand the full age spectrum of RSV morbidity and mortality burden based on statistical modelling studies, as well as the value of modelling studies in RSV disease burden estimation.

Methods

The databases Medline, Embase and Global Health were searched to identify studies published between January 1, 1995, and December 31, 2021, reporting RSV-associated excess hospitalisation or mortality rates of any case definitions using a modelling approach. All reported rates were summarised using median, IQR (Interquartile range) and range by age group, outcome and country income group; where applicable, a random-effects meta-analysis was conducted to combine the reported rates. We further estimated the proportion of RSV hospitalisations that could be captured in clinical databases.

Results

A total of 32 studies were included, with 26 studies from high-income countries. RSV-associated hospitalisation and mortality rates both showed a U-shape age pattern. Lowest and highest RSV acute respiratory infection (ARI) hospitalisation rates were found in 5–17 years (median: 1.6/100,000 population, IQR: 1.3–18.5) and < 1 year (2235.7/100,000 population, 1779.1–3552.5), respectively. Lowest and highest RSV mortality rates were found in 18–49 years (0.1/100,000 population, 0.06–0.2) and ≥ 75 years (80.0/100,000 population, 70.0–90.0) for high-income countries, respectively, and in 18–49 years (0.3/100,000 population, 0.1–2.4) and < 1 year (143.4/100,000 population, 143.4–143.4) for upper-middle income countries. More than 70% of RSV hospitalisations in children < 5 years could be captured in clinical databases whereas less than 10% of RSV hospitalisations could be captured in adults, especially for adults ≥ 50 years. Using pneumonia and influenza (P&I) mortality could potentially capture half of all RSV mortality in older adults but only 10–30% of RSV mortality in children.

Conclusions

Our study provides insights into the age spectrum of RSV hospitalisation and mortality. RSV disease burden using laboratory records alone could be substantially severely underreported for age groups ≥ 5 years. Our findings confirm infants and older adults should be prioritised for RSV immunisation programmes.

Trial registration

PROSPERO CRD42020173430.
Pyrotinib in combination with letrozole for hormone receptor-positive, human epidermal growth factor receptor 2-positive metastatic breast cancer (PLEHERM): a multicenter, single-arm, phase II trial
Authors: Hu Zhe-Yu , Yan Min , Xiong Huihua , Ran Li , Zhong Jincai , Luo Ting , Sun Tao , Xie Ning , Liu Liping , Yang Xiaohong , Xiao Huawu , Li Jing , Liu Binliang , Ouyang Quchang
Published: June 2023

Background

Human epidermal growth factor receptor 2 (HER2) targeted therapy combined with endocrine therapy has been recommended as an alternative treatment strategy for patients with hormone receptor (HR)-positive, HER2-positive metastatic breast cancer (MBC). This study aimed to evaluate the role of pyrotinib, an oral pan-HER irreversible tyrosine kinase inhibitor, in combination with letrozole for patients with HR-positive, HER2-positive MBC.

Methods

In this multi-center, phase II trial, HR-positive and HER2-positive MBC patients who were not previously treated for metastasis disease were enrolled. Patients received daily oral pyrotinib 400 mg and letrozole 2.5 mg until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the clinical benefit rate (CBR) assessed by an investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1.

Results

From November 2019 to December 2021, 53 patients were enrolled and received pyrotinib plus letrozole. As of August 2022, the median follow-up duration was 11.6 months (95% confidence interval [CI], 8.7–14.0 months). The CBR was 71.7% (95% CI, 57.7–83.2%), and the objective response rate was 64.2% (95% CI, 49.8–76.9%). The median progression-free survival was 13.7 months (95% CI, 10.7–18.7 months). The most common treatment-related adverse event of grade 3 or higher was diarrhea (18.9%). No treatment-related deaths were reported, and one patient experienced treatment discontinuation due to adverse event.

Conclusions

Our preliminary results suggested that pyrotinib plus letrozole is feasible for the first-line treatment of patients with HR-positive and HER2-positive MBC, with manageable toxicities.

Trial registration

ClinicalTrials.gov, NCT04407988.
Clinical and genetic analysis of a case of late onset carbamoyl phosphate synthase I deficiency caused by CPS1 mutation and literature review
Authors: Wang Shangyu , Chen Jinglin , Zhu Xiaoqi , Huang Tingting , Xu Haifeng , Ying Guohuan , Qian Hao , Lin Wenxin , Tung Yiehen , Khan Kaleem Ullah , Guo Hu , Zheng Guo , Lu Haiying , Zhang Gang
Published: June 2023

Background

Carbamoyl phosphate synthetase I defect (CPS1D) is a rare disease with clinical case reports mainly in early neonates or adults, with few reports of first onset in late neonatal to childhood. We studied the clinical and genotypic characteristics of children with childhood onset CPS1D caused by two loci mutations (one of these is a rarely reported non-frame shift mutation) in the CPS1.

Case presentation

We present a rare case of adolescent-onset CPS1D that had been misdiagnosed due to atypical clinical features, and further investigations revealed severe hyperammonemia (287µmol/L; reference range 11.2 ~ 48.2umol/L). MRI of the brain showed diffuse white matter lesions. Blood genetic metabolic screening showed elevated blood alanine (757.06umol/L; reference range 148.8 ~ 739.74umol/L) and decreased blood citrulline (4.26umol/L; reference range 5.45 ~ 36.77umol/L). Urine metabolic screening showed normal whey acids and uracil. Whole-exome sequencing revealed compound heterozygous mutations in the CPS1, a missense mutation (c.1145 C > T) and an unreported de novo non-frame shift mutation (c.4080_c.4091delAGGCATCCTGAT), respectively, which provided a clinical diagnosis.

Conclusion

A comprehensive description of the clinical and genetic features of this patient, who has a rare age of onset and a relatively atypical clinical presentation, will facilitate the early diagnosis and management of this type of late onset CPS1D and reduce misdiagnosis, thus helping to reduce mortality and improve prognosis. It also provides a preliminary understanding of the relationship between genotype and phenotype, based on a summary of previous studies, which reminds us that it may help to explore the pathogenesis of the disease and contribute to genetic counselling and prenatal diagnosis.
Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing
Authors: Balke-Want Hyatt , Keerthi Vimal , Gkitsas Nikolaos , Mancini Andrew G. , Kurgan Gavin L. , Fowler Carley , Xu Peng , Liu Xikun , Asano Kyle , Patel Sunny , Fisher Christopher J. , Brown Annie K. , Tunuguntla Ramya H. , Patel Shabnum , Sotillo Elena , Mackall Crystal L. , Feldman Steven A.
Published: June 2023

Background

Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma cell malignancies and could disrupt the therapeutic landscape of solid tumors. However, access to CAR-T cells is not adequate to meet clinical needs, in part due to high cost and long lead times for manufacturing clinical grade virus. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 and double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) via homology-directed repair (HDR), however yields with this approach have been limiting for clinical application (dsDNA) or access to large yields sufficient to meet the manufacturing demands outside early phase clinical trials is limited (ssDNA).

Methods

We applied homology-independent targeted insertion (HITI) or HDR using CRISPR/Cas9 and nanoplasmid DNA to insert an anti-GD2 CAR into the T cell receptor alpha constant (TRAC) locus and compared both targeted insertion strategies in our system. Next, we optimized post-HITI CRISPR EnrichMENT (CEMENT) to seamlessly integrate it into a 14-day process and compared our knock-in with viral transduced anti-GD2 CAR-T cells. Finally, we explored the off-target genomic toxicity of our genomic engineering approach.

Results

Here, we show that site directed CAR integration utilizing nanoplasmid DNA delivered via HITI provides high cell yields and highly functional cells. CEMENT enriched CAR T cells to approximately 80% purity, resulting in therapeutically relevant dose ranges of 5.5 × 108–3.6 × 109 CAR + T cells. CRISPR knock-in CAR-T cells were functionally comparable with viral transduced anti-GD2 CAR-T cells and did not show any evidence of off-target genomic toxicity.

Conclusions

Our work provides a novel platform to perform guided CAR insertion into primary human T-cells using nanoplasmid DNA and holds the potential to increase access to CAR-T cell therapies.
Assessment of data demand for informed-decisions among health facility and department heads in public health facilities of Amhara Region, northwest Ethiopia
Authors: Chanyalew Moges Asressie , Yitayal Mezgebu , Atnafu Asmamaw , Tilahun Binyam
Published: June 2023

Background

Evidence-based decision-making is a foundation of health information systems; however, routine health information is not mostly utilized by decision makers in the Amhara region. Therefore, this study aimed to explore the facility and department heads' perceptions towards the demand for and use of routine health information for decision making.

Methods

A phenomenological qualitative study was done in eight districts of the Amhara region from June 10/2019 to July 30/2019. We obtained written informed consent and recruited 22 key informants purposively. The research team prepared a codebook, assigned codes to ideas, identified salient patterns, grouped similar ideas, and developed themes from the data. Thus, data were analyzed thematically using OpenCode software.

Results

The study revealed that health workers collected many data, but little was demanded and utilized to inform decisions. The majority of respondents perceived that data were collected merely for reporting. Lack of skills in data management, analysis, interpretation, and use were the technical attributes. Individual attributes included low staff motivation, carelessness, and lack of value for data. Poor access to data, low support for Health Information System, limited space for archiving, and inadequate finance were related to organizational attributes. The contextual (social-political) factors also influenced the use of eHealth applications for improved data demand and use among health care providers.

Conclusion

In this study, health workers collect routine health data merely for reporting, and they did not demand and use it mostly to inform decisions and solve problems. Technical, individual, organizational, and contextual attributes were contributors to low demand and use of routine health data. Thus, we recommend building the technical capacity of health workers, introducing motivation mechanisms and ensuring accountability systems for better data use.
Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice
Authors: Xu Jingyi , Yang Chunshu , Zeng Siyuan , Wang Xuejiao , Yang Pingting , Qin Ling
Published: June 2023

Objectives

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE.

Methods

Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect.

Results

The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice.

Conclusion

GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.
Care pathways and factors associated with interhospital transfer to neurotrauma centers for patients with isolated moderate-to-severe traumatic brain injury: a population-based study from the Norwegian trauma registry
Authors: Cuevas-Østrem Mathias , Thorsen Kjetil , Wisborg Torben , Røise Olav , Helseth Eirik , Jeppesen Elisabeth
Published: June 2023

Background

Systems ensuring continuity of care through the treatment chain improve outcomes for traumatic brain injury (TBI) patients. Non-neurosurgical acute care trauma hospitals are central in providing care continuity in current trauma systems, however, their role in TBI management is understudied. This study aimed to investigate characteristics and care pathways and identify factors associated with interhospital transfer to neurotrauma centers for patients with isolated moderate-to-severe TBI primarily admitted to acute care trauma hospitals.

Methods

A population-based cohort study from the national Norwegian Trauma Registry (2015–2020) of adult patients (≥ 16 years) with isolated moderate-to-severe TBI (Abbreviated Injury Scale [AIS] Head ≥ 3, AIS Body < 3 and maximum 1 AIS Body = 2). Patient characteristics and care pathways were compared across transfer status strata. A generalized additive model was developed using purposeful selection to identify factors associated with transfer and how they affected transfer probability.

Results

The study included 1735 patients admitted to acute care trauma hospitals, of whom 692 (40%) were transferred to neurotrauma centers. Transferred patients were younger (median 60 vs. 72 years, P < 0.001), more severely injured (median New Injury Severity Score [NISS]: 29 vs. 17, P < 0.001), and had lower admission Glasgow Coma Scale (GCS) scores (≤ 13: 55% vs. 27, P < 0.001). Increased transfer probability was significantly associated with reduced GCS scores, comorbidity in patients < 77 years, and increasing NISSs until the effect was inverted at higher scores. Decreased transfer probability was significantly associated with increasing age and comorbidity, and distance between the acute care trauma hospital and the nearest neurotrauma center, except for extreme NISSs.

Conclusions

Acute care trauma hospitals managed a substantial burden of isolated moderate-to-severe TBI patients primarily and definitively, highlighting the importance of high-quality neurotrauma care in non-neurosurgical hospitals. The transfer probability declined with increasing age and comorbidity, suggesting that older patients were carefully selected for transfer to specialized care.
Photoaging and theory-based intervention to improve sun protection behaviors in students in Zahedan: study protocol for a randomized controlled trial
Authors: Okati-Aliabad Hassan , Hosseini Esmat Sadat , Sharifabad Mohammad Ali Morowati , Mohammadi Mahdi , Ardakani Mohamad Ebrahimzadeh , Talebrouhi Amir Hossein
Published: June 2023

Background

Excessive exposure to solar ultraviolet (UV) radiation can cause skin cancer. Implementing new technologies and computational algorithms can potentially change the outlook for cancer prevention and facilitate early detection of melanoma, thereby reducing mortality. Mobile technology as a potential provider of health services in delivering health information and conducting interventions, especially in skin fields, where a significant part of diagnosis is based on visual examination, can be important. Evidence showed that constructs of protection motivation theory (PMT) were good predictors of practicing sun protection behaviors in students. This study will investigate whether mobile applications improve safe and healthy behaviors and affect students' reduced UV exposure.

Method/design

This randomized controlled trial will be conducted on 320 students on 06/04/2022 in Zahedan. We created mobile applications (Sunshine and Skin Health and WhatsApp apps). Sunshine and Skin Health app allows users to see their changed faces in three stages of adolescence, middle age, and old age based on sun protection behavior. The WhatsApp app has 27 health messages based on PMT theory, eight educational files, and a skin cancer clip that will be sent through WhatsApp during a week. Randomization will be performed using a 1:1 (control: intervention) ratio. The primary endpoint is the group difference in sun-protective behaviors and PMT constructs immediately after the intervention. The secondary endpoint is the group difference in sun-protective behaviors and PMT constructs at a 3-month follow-up. The data will be analyzed in SPSS.22, and the significance level will be considered at 0.05.

Discussion

The present study examines the effectiveness of mobile applications in improving sun-protective behaviors. If this intervention enhances sun protection behaviors, it can prevent students’ skin damage.

Trial registration

Iranian Registry of Clinical Trials IRCT20200924048825N1. Prospectively registered on 8 February 2021.