bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating intra-action reviews at points of entry: ongoing learning opportunities during the COVID-19 pandemic
Authors: de Rooij Doret , van de Watering Miriam , van Dijk Remco , Veenstra Thijs , Appels Rolf , Swaan Corien , Timen Aura
Published: January 2023

Background

Long-lasting crises, such as the COVID-19 pandemic, require proper interim evaluation in order to optimize response. The World Health Organization and the European Center for Disease Control have recently promoted the in(tra)-action review (IAR) method for this purpose. We systematically evaluated the added value of two IARs performed in the Dutch point of entry (PoE) setting.

Methods

Two online, 4-hour IAR meetings were organized in March 2021, for ports and airports respectively, to reflect on the ongoing COVID-19 response. Topics discussed were selected through a survey among participants. Participants were mainly self-selected by the (air)port public health service. Evaluation of the IAR method consisted of participant evaluation through a questionnaire, and hot and cold debriefs of the organizing team. Evaluation of the impact of the IAR was done through analysis of the meeting results, and a 3-month follow-up of the actions proposed during the meetings.

Results

Thirty-nine professionals joined the IAR meetings. In the participant evaluation (n = 18), 89% agreed or totally agreed the IAR made it possible to identify challenges and problems in the COVID-19 response at PoE. Participants especially appreciated the resulting insight in regional and national partners. Regarding the online setting of the meeting, participants suggested to choose accessible and familiar online tools. After 3 months, all national actions and actions for ports had been executed; some regional actions for airports required further attention. A major result was a new meeting structure for all ports and the participating national authorities in which remaining and newly occurring issues were discussed.

Conclusions

Based on the evaluations, we conclude that the IAR method can be of value during long-term crises, such as the COVID-19 pandemic response. Although it is challenging to dedicate time and effort to the organization and attendance of IAR meetings during crisis, the IAR method is feasible in an online setting if appropriate organizing and technical capacity is available. A participatory set-up supports the IAR method as a starting point for continuous exchange and learning during ongoing crises.
“Assessing exposure of printing factory workers in thailand to selected heavy metals using urine and hair as non-invasive matrices”
Authors: Sirinara Patthrarawalai , Patarapongsant Yupin , Nilyai Siwaporn , Sooklert Kanidta , Dissayabutra Thasinas , Rojanathanes Rojrit , Sereemaspun Amornpun
Published: January 2023

Background

There are few thorough studies on the extent and inter-element relationships of heavy metal contamination in printing factory workers, especially in developing countries. The objective of this study was to determine the levels of eight heavy metals, including arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), cobalt (Co), lead (Pb), mercury (Hg), and manganese (Mn), in urine and scalp hair of printing industry workers, and assess inter-element correlations.

Methods

We examined a total of 85 urine samples and 85 scalp hair samples (3 cm hair segments taken from near the scalp) in 85 printing workers from a printing house in Bangkok, Thailand. We used an interviewer-administered questionnaire about participants’ printing techniques, work characteristics, and work environment. Urine and scalp hair samples were analyzed for levels of each element using the inductively coupled plasma optical emission spectrometry (ICP-OES) technique.

Results

As, Cd, Cr, Ni, Pb were detected in urine with the geometric mean concentration range of 0.0028–0.0209 mg/L, and Hg, Pb, Ni, Cd, Co, Mn, Cr were detected in hair samples (0.4453–7.165 mg/kg dry weight) of printing workers. The geometric mean Ni level was significantly higher in the urine of production line workers than back-office personnel (0.0218 mg/L vs. 0.0132 mg/L;p = 0.0124). The other elements did not differ significantly between production line and back-office workers in either urine or hair. There was also a strong, statistically significant positive correlation between Ni and Co levels in hair samples of workers (r = 0.944,p < 0.0001).

Conclusions

Average concentrations of most of the metals in urine and hair of printing workers were found to be above the upper reference values. The significantly higher concentrations of Ni in production line workers might be due to more exposure to printed materials. A strong inter-element correlation between Ni and Co in hair samples can increase stronger health effects and should be further investigated. This study reveals possible dependencies and impact interactions of heavy metal exposure in printing factory workers.
Application of 3D printed pelvic fracture related urethra and surrounding tissue as preoperative planning model
Authors: Zhang Kaile , Liu Jiafu , Wang Liyang , Li Wenyao , Qi Er , Fu Qiang
Published: January 2023

Objective

Urethral stenosis caused by pelvic fracture urethral injury (PFUI) is a complex urological disease, especially for the redo cased. However, to find the proximal end of the posterior urethra, and to avoid injury to the rectum and to forecast to remove the inferior pubic margin are two key points for a successful surgery. These steps can be challenging for even the most experienced urologists. This study is to describe a new technique for understanding the three-dimensional (3D) anatomy of the urethra, which will also aid in surgical planning and simplify urethroplasty.

Materials and methods

Three patients underwent routine urethroscopy, X ray urethrography and contrast CT urethrography. The 3D images were then reconstructed, and the data were transmitted to a 3D printer. 3D models were printed with polyacrylic acid to simulate the anatomical structure and relationship of urethral stenosis with pubic symphysis and rectum. Various diagnosis methods were compared with the condition in surgery. The patients and trainee questionnaires were performed.

Results

Three models of urethral CT were obtained. These models were presented to patients and trainee doctors along with routine urethroscopy, urethrography, and urethral CT. The scores of patients and trainee question forms demonstrated that the 3D printed urethral stenosis model of pelvic fracture has obvious advantages in urethral adjacency and ease of understanding. The 3D printed urethras were easy to show the pubic symphysis and simulate its excision and exposure of urethra. The model could show the precise distance from urethra to rectum to prevent the rectum injury in surgery.

Conclusions

3D printing technology can be applied to the preoperative evaluation of urethral stenosis caused by PFUI. It can be auxiliary to understand the anatomical structure of the posterior urethra, the direction of urethral displacement, protecting the rectum and the forecasting for pubectomy. It is especially helpful for the accurate preoperative planning of some complex urethral stenosis and redo cases.
Reduced antibody response to SARS-CoV-2 in COVID-19 patients with newly diagnosed diabetes: a retrospective observational study
Authors: Otsubo Naoya , Fukuda Tatsuya , Beppu Hiroko , Maki Chisato , Yasui Fumihiko , Hanawa Tomohide , Sugita Chise , Murakami Masanori , Yamada Tetsuya , Kohara Michinori , Wakai Sachiko
Published: January 2023

Background

The coronavirus disease 2019 (COVID-19) pandemic has dramatically impacted global health, and patients with type 2 diabetes have been identified as a high-risk group for COVID-19 infection and the development of severe disease. In response, this study aimed to evaluate whether patients with type 2 diabetes infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could develop antibody responses in the same manner as patients without diabetes, and whether there is a difference in antibody response to SARS-CoV-2 between patients with diabetes diagnosed prior to hospitalization, and those with newly diagnosed diabetes.

Methods

SARS-CoV-2-specific immunoglobulin G (IgG) levels were quantified using two iFlash 3000 Chemiluminescence Immunoassay analyzer kits (Shenzhen YHLO Biotech Co., Ltd.) to detect IgG antibodies specific for nucleocapsid protein (IgG-N), and specific for the S1 subunit of the spike protein (IgG-S1). In 124 hospitalized patients with COVID-19, 40 patients with type 2 diabetes were matched to 40 patients without diabetes using propensity score matching (PSM).

Results

There was no difference in IgG-N and IgG-S1 levels between the patients with diabetes and those without. Of patients with diabetes, 31 patients had known diabetes and nine patients had newly diagnosed diabetes. The median levels of IgG-N at 7–13 days in patients with newly diagnosed diabetes were significantly lower than those in patients with known diabetes (IgG-N; 10.9 vs. 31.0 AU/mL, p = 0.031, IgG-S1; 7.5 vs. 24.4 AU/mL, p = 0.023).

Conclusions

Even after adjusting for covariates using PSM, COVID-19 patients with type 2 diabetes had comparable antibody responses to patients without diabetes. Patients with newly diagnosed diabetes had lower IgG-N and IgG-S1 production in the second week of the disease compared with those with previously known diabetes.
Effect of educational intervention based on PRECEDE model on lifestyle modification, self-management behaviors, and hypertension in diabetic patients
Authors: Khani Jeihooni Ali , Sobhani Ali , Afzali Harsini Pooyan , Amirkhani Mehdi
Published: January 2023

Background

Inappropriate lifestyle and poor self-management in diabetic patients lead to many complications including hypertension and increased disease burden. Because of insufficient studies on Effect of educational interventions on lifestyle, self-management and hypertension in diabetic patients, the present study aimed to evaluate the Effect of educational intervention based on PRECEDE model on lifestyle, self-management, and hypertension of diabetic patients.

Methods

This clinical trial was conducted on 300 diabetic patients with hypertension. The patients were selected using simple random sampling and divided into 2 groups of intervention (150 people) and control (150 people). The intervention group was trained through ten 50–55 min sessions on lifestyle skills, self-management, and hypertension control based on the PRECEDE model. Before and after the intervention, lifestyle skills, self-management, and PRECED model constructs were evaluated using a standard questionnaire. Data were analyzed by SPSS 20 software using t-test, Kolmogorov–Smirnov, and Chi-Square tests (P < 0.05).

Results

In the intervention group, the mean score of different dimensions of lifestyle and self-management significantly increased from 110.45 ± 18.78 to 172.58 ± 186.66 and 64.33 ± 15.24 to 144.32 ± 15.82, respectively (P = 0.001). Mean systolic and diastolic blood pressure also decreased from 148.5 ± 5.39 to 123.54 ± 5.32 and 95.41 ± 3.12 to 72.24 ± 3.06 (P < 0.001). Moreover, the mean score of all the PRECEDE model constructs significantly increased after the intervention. In the control group, the mean score of the PRECEDE model constructs, the dimensions of lifestyle, self-management, and systolic and diastolic blood pressure did not change significantly before and after the intervention (P > 0.05).

Conclusion

‌ Based on the study's results, the PRECEDE model was found to be a non-invasive, non-pharmacological, cost-effective method without any complication and as a complementary action along with other methods in the treatment of diabetic patients.
Contribution of information about acute and geriatric characteristics to decisions about life-sustaining treatment for old patients in intensive care
Authors: Beil Michael , van Heerden P. Vernon , de Lange Dylan W. , Szczeklik Wojciech , Leaver Susannah , Guidet Bertrand , Flaatten Hans , Jung Christian , Sviri Sigal , Joskowicz Leo
Published: January 2023

Background

Life-sustaining treatment (LST) in the intensive care unit (ICU) is withheld or withdrawn when there is no reasonable expectation of beneficial outcome. This is especially relevant in old patients where further functional decline might be detrimental for the self-perceived quality of life. However, there still is substantial uncertainty involved in decisions about LST. We used the framework of information theory to assess that uncertainty by measuring information processed during decision-making.

Methods

Datasets from two multicentre studies (VIP1, VIP2) with a total of 7488 ICU patients aged 80 years or older were analysed concerning the contribution of information about the acute illness, age, gender, frailty and other geriatric characteristics to decisions about LST. The role of these characteristics in the decision-making process was quantified by the entropy of likelihood distributions and the Kullback–Leibler divergence with regard to withholding or withdrawing decisions.

Results

Decisions to withhold or withdraw LST were made in 2186 and 1110 patients, respectively. Both in VIP1 and VIP2, information about the acute illness had the lowest entropy and largest Kullback–Leibler divergence with respect to decisions about withdrawing LST. Age, gender and geriatric characteristics contributed to that decision only to a smaller degree.

Conclusions

Information about the severity of the acute illness and, thereby, short-term prognosis dominated decisions about LST in old ICU patients. The smaller contribution of geriatric features suggests persistent uncertainty about the importance of functional outcome. There still remains a gap to fully explain decision-making about LST and further research involving contextual information is required.

Trial registration: VIP1 study: NCT03134807 (1 May 2017), VIP2 study: NCT03370692 (12 December 2017).
The impact of triglyceride-glucose index on ischemic stroke: a systematic review and meta-analysis
Authors: Yang Ying , Huang Xiangting , Wang Yuge , Leng Lin , Xu Jiapei , Feng Lei , Jiang Shixie , Wang Jiang , Yang Yanrong , Pan Gaofeng , Jiang Bing , Wang Yan , Chen Lan
Published: January 2023

Background

Strokes significantly impair quality of life and incur high economic and societal burdens. The triglyceride and glucose (TyG) index is a biochemical marker of insulin resistance (IR) and may have important value in the prediction of strokes, especially ischemic stroke (IS). Our study aims to investigate the relationship between TyG index and IS and ascertain whether TyG index is independently associated with IS adverse outcomes.

Methods

The Cochrane, Embase, Medline, Web of Science, PubMed, and other relevant English databases and related websites were systematically searched for articles on ‘‘TyG index’’ and "stroke" published from inception to April 4, 2022. We reviewed the available literature on the TyG index and its relation to predicting IS occurrence in the general population and adverse clinical outcomes. We calculated odds ratios (OR) of TyG index and its predictability of IS occurrence and adverse outcomes. Statistical analyses were performed using the Meta Package in STATA, version 12.0.

Results

A total of 18 studies and 592,635 patients were included in our analysis. The pooled effect values of all stroke types showed that higher TyG index was associated with increased the risk of IS in the general population (OR 1.37; 95% CI 1.22–1.54) in a total sample of 554,334 cases with a high level of heterogeneity (P = 0.000, I2 = 74.10%). In addition, compared to IS patients with a lower TyG index, IS patients with a higher TyG index was associated with higher risk of stroke recurrence (OR: 1.50; 95% CI 1.19–1.89) and increased risk of mortality (OR 1.40 95% CI 1.14–1.71). No correlation was found in the effect value combinations of poor functional outcomes (OR 1.12; 95% CI 0.88–1.43) and neurological worsening (OR: 1.76; 95% CI 0.79–3.95) in a total sample of 38,301 cases with a high level of heterogeneity (P = 0.000; I2 = 77.20%).

Conclusions

TyG index has potential value in optimizing risk stratification for IS in the general population. Furthermore, there is a significant association between high TyG index and many adverse outcomes of stroke, especially stroke recurrence and high mortality. Future studies should focus on multi-center and multi-regional designs in order to further explore the relationship between IS and TyG index.
Understanding the rise in traditional contraceptive methods use in Uttar Pradesh, India
Authors: Namasivayam Vasanthakumar , Dehury Bidyadhar , Prakash Ravi , Becker Marissa , Anand Preeti , Mishra Ashish , Singhal Shreya , Halli Shivalingappa , Blanchard James , Spears Dean , Isac Shajy
Published: January 2023

Background

The sustainable development goals (SDG) aim at satisfying three-fourths of family planning needs through modern contraceptive methods by 2030. However, the traditional methods (TM) of family planning use are on the rise, along with modern contraception in Uttar Pradesh (UP), the most populous Indian state. This study attempts to explore the dynamics of rising TM use in the state.

Methods

We used a state representative cross-sectional survey conducted among 12,200 Currently Married Women (CMW) aged 15–49 years during December 2020–February 2021 in UP. Using a multistage sampling technique, 508 primary sampling units (PSU) were selected. These PSU were ASHA areas in rural settings and Census Enumeration Blocks in urban settings. About 27 households from each PSU were randomly selected. All the eligible women within the selected households were interviewed. The survey also included the nearest public health facilities to understand the availability of family planning methods. Univariate and bivariate analyses were conducted. Appropriate sampling weights were applied.

Results

Overall, 33.9% of CMW were using any modern methods and 23.7% any TM (Rhythm and withdrawal) at the time of survey. The results show that while the modern method use has increased by 2.2 percentage points, the TM use increased by 9.9 percentage points compared to NFHS-4 (2015–16). The use of TM was almost same across women of different socio-demographic characteristics. Of 2921 current TM users, 80.7% started with TM and 78.3% expressed to continue with the same in future. No side effects (56.9%), easy to use (41.7%) and no cost incurred (38.0%) were the main reasons for the continuation of TM. TM use increased despite a significant increase (66.1 to 81.3%) in the availability of modern reversible methods and consistent availability of limiting methods (84.0%) in the nearest public health facilities.

Conclusion

Initial contraceptive method was found to have significant implications for current contraceptive method choice and future preferences. Program should reach young and zero-parity women with modern method choices by leveraging front-line workers in rural UP. Community and facility platforms can also be engaged in providing modern method choices to women of other parities to increase modern contraceptive use further to achieve the SDG goals.
Immunosenescence and inflammaging in the aged horse
Authors: DeNotta Sally , McFarlane Dianne
Published: January 2023

The equine population in the United States and worldwide now includes a higher percentage of geriatric horses than ever previously recorded, and as methods to treat and manage elderly equids are developed and refined, this aging population will likely continue to expand. A better understanding of how horses age and the effect of age on immunity and disease susceptibility is needed to enable targeted preventative healthcare strategies for aged horses. This review article outlines the current state of knowledge regarding the effect of aging on immunity, vaccine responsiveness, and disease risk in the horse, highlighting similarities and differences to what is observed in aged humans. Horses show similar but milder age-related alterations in immune function to those reported in people. Decreases in lymphocyte proliferation and antibody production and diminished response to vaccination have all been documented in elderly horses, however, increased risk of infectious disease is not commonly reported. Aged horses also show evidence of a proinflammatory state (inflammaging) yet appear less susceptible to the chronic diseases of people for which inflammation is a risk factor. Information is currently lacking as to why the horse does not experience the same risk of age-related disease (e.g., cancer, heart disease, neurodegeneration) as people, although a lack of negative lifestyle habits, differences in diet, exercise, genetics and physiology may all contribute to improved health outcomes in the older horse.
The impacts of COVID-19 pandemic on service delivery and treatment outcomes in people living with HIV: a systematic review
Authors: SeyedAlinaghi SeyedAhmad , Mirzapour Pegah , Pashaei Zahra , Afzalian Arian , Tantuoyir Marcarious M. , Salmani Roghayeh , Maroufi Seyed Farzad , Paranjkhoo Parinaz , Maroufi Seyede Parmis , Badri Hajar , Varshochi Sanaz , Vahedi Farzin , Mehraeen Esmaeil , Dadras Omid
Published: January 2023

Introduction

The COVID-19 epidemic and various control and mitigation measures to combat the widespread outbreak of the disease may affect other parts of health care systems. There is a concern that the COVID-19 pandemic could disrupt HIV services. Therefore, this study aimed to systematically evaluate the effect of the COVID-19 pandemic on service delivery and treatment outcomes in people with HIV.

Methods

In this study, a systematic search was conducted using the keywords in the online databases including Scopus, PubMed, Web of Science, and Cochrane databases. The retrieved articles underwent a two-step title/abstract and full-text review process, and the eligible papers were selected and included in the qualitative synthesis.

Result

We selected 16 studies out of 529 retrieved records that met the inclusion criteria for this review. Study populations of the selected studies were either HIV-positive patients or HIV clinics and healthcare providers. Most studies were focused on adhering to and obtaining medication and attending clinical appointments and their decrement during the pandemic. Other aspects of HIV care (alternative healthcare settings, viral suppression, psychological care, etc.) were discussed to a lesser extent by the included studies.

Conclusion

Interruption in in-person visits and medical follow-up services, loss of adherence to treatment, and subsequent increase in mortality due to the COVID-19 pandemic complications in PLHIV have led to growing concerns. Other challenges were psychological disorders such as anxiety and depression, an increase in substance abuse, and a rise in experienced stigma and discrimination. However, the use of telemedicine in some countries helps to alleviate the situation to some extent and is recommended in similar settings in the future.
Faculty, staff, and student perceptions of substance use disorder stigma in health profession training programs: a quantitative study
Authors: Barenie Rachel E. , Cernasev Alina , Heidel R. Eric , Stewart Steven , Hohmeier Kenneth
Published: January 2023

Background

Research indicates that stigma impacts the care provided to individuals with Substance Use Disorders (SUDs), but perceptions of SUDs in various healthcare training programs are not well known. We aimed to characterize perceptions of faculty, staff, and students about SUD stigma in professional healthcare training programs.

Methods

We conducted a cross-sectional survey of faculty, staff, and students employed at or enrolled in one of six health-related colleges at one Mid-South health science center in the United States, including medicine, pharmacy, dentistry, nursing, health professions, and graduate health sciences. Data collection occurred between February and March 2021. We used descriptive and frequency statistics to assess the constructs within the survey instrument.

Results

A total of 572 respondents participated in this study (response rate = 9%; students,n = 428, 75%; faculty,n = 107, 19%; staff,n = 32, 6%). Most respondents reported interacting with persons with a SUD, cited challenges with the interaction, and perceived SUDs to be mental health condition (n = 463) or biological disease (n = 326). Most respondents believed that their college: emphasizes learning about SUDs; promotes an accurate perception of SUDs; and fosters respect for persons with. Few respondents reported they hear faculty, staff, or students express negative comments about persons with SUDs, but they were sometimes expressed by students.

Conclusions

Most faculty, staff, and students reported experiencing challenges when interacting with a person with a SUD, mainly communication, but few recalled hearing negative comments from their peers. Whether interventions tailored towards improving communication in academic healthcare training settings could minimize challenges experience by faculty, staff, and students when serving individuals with SUDs should be further evaluated.
Preliminary outcomes following revision total knee arthroplasty using a new fixed-bearing revision knee system in Asians: a mean of 3-year follow-up
Authors: Shon Oog-Jin , Kim Gi Beom , Kim Hyuck Goo
Published: January 2023

Purpose

The purpose of this study was to investigate the early outcomes of the new semi-constrained revision total knee arthroplasty (TKA) system by performing subgroup analysis according to the revision cause.

Materials and methods

From August 2019 to July 2020, 83 revision TKAs using the fixed-bearing Attune® revision knee system with a minimum follow-up of 2 years were retrospectively reviewed. Clinically, the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, the Western Ontario and McMaster Universities Osteoarthritis Index, and range of motion (ROM) were evaluated. The incidence of systemic and specific postoperative complications was investigated. Each cohort was divided into septic (group A, 34 patients) and aseptic mode (group B, 41 patients), and compared to assess the outcomes.

Results

The mean age at the time of revision was 73.3 years (range 59.0 to 84.0 years), and the follow-up duration was 36.1 months (range 30.0 to 40.0 months). Clinical outcomes and ROM significantly improved at last follow-up (p < 0.001). Group A showed statistically inferior clinical outcomes in the last follow-up compared to group B. Four knees (5.3%) had a postoperative femoral joint line elevation of more than 5 mm. There were no serious systemic complications. One patient underwent re-revision TKA due to recurrence of infection. No stem tip impingement or cortical erosion was observed in all patients.

Conclusions

Revision TKAs using a new semi-constrained revision system showed favorable short-term follow-up outcomes, with improvement in clinical scores and ROM. Moreover, by using stem offsets, no postoperative stem tip impingement or cortical erosion was found.

Level of evidence

Level IV, Retrospective Case Series.
The German version of the neurofibromatosis 2 impact on quality of life questionnaire correlates with severity of depression and physician-reported disease severity
Authors: Lawson McLean Anna Cecilia , Freier Anna , Lawson McLean Aaron , Kruse Johannes , Rosahl Steffen
Published: January 2023

Background

Neurofibromatosis type 2 (NF2) is a rare genetic disease that causes a wide range of disabilities leading to compromised quality of life (QOL). There is clear need for a validated disease-specific tool to assess quality of life among German-speaking patients with neurofibromatosis type 2 (NF2). The NFTI-QOL questionnaire has produced useful results in English-speaking cohorts. The aim of this study was to produce and validate a German version of the NFTI-QOL (NFTI-QOL-D) and to correlate QOL scores with a depression score (PHQ-9) and clinical disease severity.

Methods

The original English-language NFTI-QOL was translated into German and then back-translated in order to preserve the questionnaire’s original concepts and intentions. A link to an online survey encompassing the NFTI-QOL-D and the PHQ-9 depression questionnaire was then sent to 97 patients with NF2 by email. The respondents’ scores were compared to clinician-reported disease severity scores.

Results

77 patients completed the online survey in full. Internal reliability among NFTI-QOL-D responses was strong (Cronbach’s alpha: 0.74). Both PHQ-9 and clinician disease severity scores correlated with NFTI-QOL-D scores (Pearson’s rho 0.63 and 0.62, respectively).

Conclusions

The NFTI-QOL-D is a reliable and useful tool to assess patient-reported QOL in German-speaking patients with NF2. The correlation of QOL with both psychological and physical disease parameters underlines the importance of individualized interdisciplinary patient care for NF2 patients, with attention paid to mental well-being as well as to somatic disease manifestations.
ODs with a positive TPR conclusion, not subject to a conditional approval, and approved without requiring a PASS would be more likely to be reimbursed in Spain
Authors: Poveda José Luis , Gómez Claudia , Gil Alicia , Badia Xavier
Published: January 2023

Background

The present study aims to assess clinical and regulatory variables that would influence pricing and reimbursement (P&R) decisions for Orphan Drugs (ODs) in Spain. ODs approved by the European Commission (EC) between 2006 and 2021 were classified according to their P&R status in Spain: approved, undergoing decision and rejected. A statistical analysis was carried out to assess the potential association between clinical and regulatory variables and P&R decision of ODs in Spain: therapeutic area, rarity of disease, existence of alternative therapies, availability of survival-related outcomes, safety profile, type of population, conditional approval status granted by the European Medicines Agency (EMA) and a positive Therapeutic Positioning Report (TPR) opinion.

Results

111 ODs have been approved by the EC and have obtained marketing authorisation in Spain between 2006 and 2021. Out of the 111 ODs, 57 (51.4%) were reimbursed, 24 (21.6%) were undergoing decision and 30 (27%) were rejected. According to the statistical analysis, ODs with a positive TPR conclusion (p-value < 0.01), not subject to a conditional approval by the EMA (p-value < 0.05) and approved without the obligation to conduct a post-authorisation safety study (PASS) (p-value < 0.05), were statistically significant, and therefore, would be more likely to obtain P&R approval in Spain.

Conclusions

This study shows that the TPR plays a key role in the P&R process in Spain and highlights that traditional evaluation tools, such us safety and efficacy, were the main drivers of P&R decisions for ODs. A positive conclusion of the TPR, non-conditional approval by the EMA and no obligation for a PASS seems to favourably affect P&R decisions in Spain.
Overexpression the BnLACS9 could increase the chlorophyll and oil content in Brassica napus
Authors: Zhu Keming , Li Nannan , Zheng Xiangfeng , Sarwar Rehman , Li Yulong , Cao Jun , Wang Zheng , Tan Xiaoli
Published: January 2023

Background

Chlorophyll is a very important pigment involved in photosynthesis, while plant acyl-CoA biosynthesis is derived from plastid-localized fatty acids (FAs). Until now, the regulation of the acyl-CoA pathway for chlorophyll biosynthesis is still unknown.

Results

Here, we identified a long-chain acyl-CoA synthetase (LACS) gene BnLACS9 from Brassica napus. BnLACS9 complemented a LACS-deficient yeast strain YB525, which indicated that BnLACS9 has the LACS function. BnLACS9 was localized in the chloroplast envelope membrane, while mainly expressed in young leaves and flowers. Overexpression of BnLACS9 in Nicotiana benthamiana resulted in an increase in total CoA and MGDG content. In B. napus with overexpression of BnLACS9, the number of chloroplast grana lamellae and the chlorophyll content, as well as the MGDG and DGDG contents, increased compared to wild type. The net photosynthetic rate, dry weight of the entire plant and oil content of seeds increased significantly, accompanied by an increase in chlorophyll content. Transcriptome analysis revealed that overexpression of BnLACS9 improved the pathway of acyl-CoA biosynthesis and further improved the enzymes in the glycolipid synthesis pathway, while acyl-CoA was the substrate for glycolipid synthesis. The increased glycolipids, especially MGDG and DGDG, accelerated the formation of the chloroplast grana lamellae, which increased the number of chloroplast thylakoid grana lamella and further lead to increased chlorophyll content.

Conclusions

In the present study, we demonstrated that BnLACS9 played a crucial role in glycolipids and chlorophyll biosynthesis in B. napus. The results also provide a new direction and theoretical basis for the improvement of the agronomic traits of plants.
Dementia and psychotropic medications are associated with significantly higher mortality in geriatric patients hospitalized with COVID-19: data from the StockholmGeroCovid project
Authors: Secnik Juraj , Eriksdotter Maria , Xu Hong , Annetorp Martin ,   on behalf of the SweGeroCOVID Project, Rytarowski Aleksander , Johnell Kristina , Hägg Sara , Religa Dorota
Published: January 2023

Background

Dementia and psychotropic medications are discussed as risk factors for severe/lethal outcome of the coronavirus disease 2019 (COVID-19). We aimed to explore the associations between the presence of dementia and medication use with mortality in the hospitalized and discharged patients who suffered from COVID-19.

Methods

We conducted an open-cohort observational study based on electronic patient records from nine geriatric care clinics in the larger Stockholm area, Sweden, between February 28, 2020, and November 22, 2021. In total, we identified 5122 hospitalized patients diagnosed with COVID-19, out of which 762 (14.9%) patients had concurrent dementia and 4360 (85.1%) were dementia-free. Patients’ age, sex, baseline oxygen saturation, comorbidities, and medication prescription (cardiovascular and psychotropic medication) were registered at admission. The hazard ratios (HRs) with 95% confidence intervals (CIs) of in-hospital, 30-day, 90-day, 365-day post-discharge, and overall mortality during the follow-up were obtained. Then, the associations of dementia and medication use with mortality were determined using proportional hazards regression with time since entry as a time scale.

Results

After adjustment, dementia was independently associated with 68% higher in-hospital mortality among COVID-19 patients compared to patients who were dementia-free at admission [HRs (95% CI) 1.68 (1.37–2.06)]. The increase was consistent post-discharge, and the overall mortality of dementia patients was increased by 59% [1.59 (1.40–1.81)]. In addition, the prescription of antipsychotic medication at hospital admission was associated with a 70% higher total mortality risk [1.70 (1.47–1.97)].

Conclusions

The clinical co-occurence of dementia and COVID-19 increases the short- and long-term risk of death, and the antipsychotics seem to further the risk increase. Our results may help identify high-risk patients in need of more specialized care when infected with COVID-19.
Role of Immunotherapy in Breast Cancer
Authors: Jacob Saya L. , Huppert Laura A. , Rugo Hope S.
Published: January 2023

The advent of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment of solid tumor malignancies. In breast cancer, the most robust data to date for ICI exist for triple-negative breast cancer (TNBC). Preclinical studies suggested increased antitumoral immune response in patients with TNBC undergoing ICI treatment. Early clinical trials investigated the use of ICI monotherapy in patients with metastatic TNBC with promising results, particularly in the first-line setting and for those patients whose tumors had high programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) expression. Subsequent trials evaluated the use of ICI in combination with conventional chemotherapy to enhance the host immune response. Pembrolizumab combined with chemotherapy in the KEYNOTE-355 study resulted in improved progression-free survival and overall survival benefits for patients with PD-L1 combined positive score > 10 metastatic TNBC. In early-stage disease, two phase III trials demonstrated increased rates of pathologic complete response at the time of surgery with the addition of neoadjuvant ICI to standard chemotherapy. The large KEYNOTE-522 trial showed improved event-free survival with neoadjuvant and adjuvant ICI. Several biomarkers have been identified, which may be predictive of response to ICI therapy including PD-1/PD-L1 expression, tumor mutational burden, tumor-infiltrating lymphocytes, and multigene assays capturing favorable immune cell signatures. For hormone receptor–positive and human epidermal growth factor receptor–positive breast cancer, there are ongoing studies evaluating ICI therapy in combination with chemotherapy and targeted agents. Finally, across all subtypes, several novel immunotherapeutic agents are under investigation including novel ICIs, cancer vaccines, adoptive cellular therapy, and oncolytic viruses.
Self-Assembly Strategies for Graphene Oxide/Silica Nanostructures: Synthesis and Structural Analysis
Authors: Takeuchi Yuki , Ohkura Kentaro , Nishina Yuta
Published: January 2023

Nanostructured 3D silica-based materials can be designed using a low-dimensional template. Various composites composed of graphene oxide (GO) and silica have been investigated. However, to improve the performance of GO/silica nanostructure (GSN), the exploitation of the assembly method and the effect of combining GO and silica on the hybrid structure need to be elucidated. In this study, novel mesoporous GSNs were developed using two self-assembly methods: particle attaching-induced self-assembly (PAISA) and polymerization- and evaporation-induced self-assembly (PEISA). The synthesized GSNs obtained using each method were analyzed to determine the effect of combining silica with GO in each method on the porosity of GSNs. The former method introduced silica nanoparticles into GO, and aligned pores similar to the particle size were formed. In the latter method, synthesized GSN had broad mesopores, and a higher surface area derived from the silica particles randomly formed inside/outside GO layers. Both GSNs have specific surface areas close to that of the introduced silica, suggesting that the porosity of GSNs can be controlled by selecting the appropriate silica structure and its synthesis. Furthermore, GSN had a higher pore volume than silica itself, suggesting the formation of a hierarchical structure by introducing GO.
Concussion and Psychological Effects: A Review of Recent Literature
Authors: Barela Matthew , Wong Allen , Chamberlain Rachel
Published: January 2023

The aim of this article is to provide an up-to-date review of psychological changes in association with postconcussive athletes. In particular, this article focused on the symptomatology, risk factors, and treatment of psychiatric diagnoses in patients who suffered a sports-related concussion (SRC). After an extensive review of prior and current literature, there is significant evidence that demonstrates an association of changes in mood and behavior, including new or worsening symptoms of anxiety, depression, and difficulty with attention and concentration in those who are recovering from a concussion. The goal of care in these patients is to identify and treat these psychological symptoms early to have more favorable long-term outcomes. Primary treatment should focus on psychotherapy; however, other considerations may be warranted in certain cases, such as selective serotonin reuptake inhibitors for depression and tricyclic antidepressants and gabapentin for short-term cognitive symptom improvement.
Lessons learned from independent external validation of an AI tool to detect breast cancer using a representative UK data set
Authors: Cushnan Dominic , Young Kenneth C , Ward Dominic , Halling-Brown Mark D , Duffy Stephen , Given-Wilson Rosalind , Wallis Matthew G , Wilkinson Louise , Lyburn Iain , Sidebottom Richard , McAvinchey Rita , Lewis Emma B , Mackenzie Alistair , Warren Lucy M
Published: January 2023

Objective:

To pilot a process for the independent external validation of an artificial intelligence (AI) tool to detect breast cancer using data from the NHS breast screening programme (NHSBSP).

Methods:

A representative data set of mammography images from 26,000 women attending 2 NHS screening centres, and an enriched data set of 2054 positive cases were used from the OPTIMAM image database. The use case of the AI tool was the replacement of the first or second human reader. The performance of the AI tool was compared to that of human readers in the NHSBSP.

Results:

Recommendations for future external validations of AI tools to detect breast cancer are provided. The tool recalled different breast cancers to the human readers. This study showed the importance of testing AI tools on all types of cases (including non-standard) and the clarity of any warning messages. The acceptable difference in sensitivity and specificity between the AI tool and human readers should be determined. Any information vital for the clinical application should be a required output for the AI tool. It is recommended that the interaction of radiologists with the AI tool, and the effect of the AI tool on arbitration be investigated prior to clinical use.

Conclusion:

This pilot demonstrated several lessons for future independent external validation of AI tools for breast cancer detection.

Advances in knowledge

Knowledge has been gained towards best practice procedures for performing independent external validations of AI tools for the detection of breast cancer using data from the NHS Breast Screening Programme.
Important parameters for cost-effective implementation of lung cancer
screening
Authors: Morgan Helen , Baldwin David R
Published: January 2023

It is now widely accepted that lung cancer screening through low-dose computed tomography (LDCT) results in fewer diagnoses at a late stage, and decreased lung cancer mortality. Whilst reducing deaths from lung cancer is an essential prerequisite, this must be balanced against the considerable economic costs accumulated in screening. Multiple health economic models have shown substantial variation in cost per Quality-Adjusted Life Year (QALY), partly driven by the healthcare costs in the country concerned and partly by other modifiable programme components. Recent modelling using UK costs and a targeted approach suggest that most scenarios are within the willingness to pay threshold for the UK. However, identifying the most clinically and cost-effective programme is a priority to minimise the total financial impact. Programme components that influence cost-effectiveness include the method of selection of the eligible population, the participation rate, the interval between rounds of screening, the method of pulmonary nodule management, and the approach to clinical work up. Future research will clarify if a personalised approach to screening, using baseline and subsequent risk to define screening intervals is more cost-effective. The burden of LDCT screening on the medical infrastructure and workforce has to be quantified and carefully managed during implementation.
Evaluation of distal femoral and proximal tibial epiphyseal plate in bone age estimation with 3.0T MRI: a comparison of current methods
Authors: Has Busra , Gurses Murat Serdar , Altinsoy Hasan Baki
Published: January 2023

Objective:

Dedouit et al, Kramer et al and Vieth et al defined different staging methods over different sequences in knee MRI for bone age determination. Our study aims to examine three different methods in which the maturation stages of the knee epiphyses are evaluated by MRI in the same population, to compare the methods and results and evaluate them for some age thresholds and to discuss their applicability in forensic age estimation.

Methods:

In this study, 597 knee images obtained using a 3.0T MR scanner were evaluated retrospectively. The T 1 weighted and proton density-weighted sequences were evaluated by two observers. Knee bone development was staged on the femur and tibia, and descriptive statistics were calculated for each stage according to age and sex. Descriptive statistics were presented according to the age and sex of the cases, and intra- and interobserver agreements were evaluated by the κ and κw statistics obtained by the Fleiss approach.

Results:

Significant changes were found in stages depending on age. The intra- and interobserver agreement levels were very good (κ > 0.80) for each method. The methods of Dedouit, Kramer and Vieth can be used as an additional criteria for forensic age estimation for 14, 15, 18 and 21 year thresholds.

Conclusion:

Knee MRI stands out as an alternative modality for age estimation and it is necessary to prefer the method intended for the investigated age range with an individual-specific approach.

Advances in knowledge:

Our study stands out as the first study in which current classification methods were applied and compared in the same population for age estimation with knee MRI.
Improving image quality with deep learning image reconstruction in double-low-dose head CT angiography compared with standard dose and adaptive statistical iterative reconstruction
Authors: Huang Xin , Zhao Wenzhe , Wang Geliang , Wang Yiming , Li Jianying , Li Yanshou , Zeng Qiang , Guo Jianxin
Published: January 2023

Objective:

To demonstrate similar image quality with deep learning image reconstruction (DLIR) in reduced contrast medium (CM) and radiation dose (double-low-dose) head CT angiography (CTA), in comparison with standard-dose and adaptive statistical iterative reconstruction-Veo (ASIR-V).

Methods:

A prospective study was performed in 63 patients who under head CTA using 256-slice CT. Patients were randomized into either the standard-dose group (n = 38) with 40 ml of Iopromide (370 mgI ml−1 at 4.5 ml s−1); or a double-low-dose group (n = 25) with CM of 25 ml at 3.0 ml s−1. For image reconstruction, the double-low-dose group used DLIR-M and DLIR-H strength, and the standard-dose group used ASIR-V with 50% strength. The CT value and standard deviation, signal-to-noise ratio and contrast-to-noise ratio of posterior fossa, neck muscles, carotid, vertebral and middle cerebral arteries were measured. The image noise, vessel edge and structure blurring and overall image quality were assessed by using a 5-grade method. The double-low-dose group reduced CM dose by 37.5% and CT dose index by 41% compared with the standard-dose group. DLIR further reduced the standard deviation value of the middle cerebral artery and posterior fossa and provided better overall subjective image quality (p < 0.05).

Conclusion:

DLIR significantly reduces image noise and provides higher overall image quality in the double-low-dose CTA.

Advances in knowledge

It is feasible to reduce CM dose by 37.5% and volume CT dose index by 41% with the combination of 80 kVp and DLIR in head CTA. Compared with ASIR-V, DLIR further reduces image noise and achieves better image quality with reduced contrast and radiation dose.