bluuebunny/crossref_metadata_2025 huggingface dataset:
Causes and outcomes of at-risk underperforming pharmacy students: implications for policy and practice
Authors: Campbell Alice , Hinton Tina , da Costa Narelle C. , O’Brian Sian E. , Liang Danielle R. , Wheate Nial J.
Published: April 2024

Objective

This study aimed to understand the key determinants for poor academic performance of students completing a Bachelor of Pharmacy (BPharm), Bachelor of Pharmacy and Management (BPharmMgmt), or Master of Pharmacy (MPharm) degree.

Methods

Data were collected on pharmacy students who had not met academic progression requirements between 2008 and 2018 at The University of Sydney, Australia. This included: age at the start of pharmacy degree; gender; whether they transferred from another university; whether they were a domestic or international student; Australian Tertiary Admissions Rank upon entry, previous studies in biology, chemistry, or mathematics; show cause triggers (units of study failed); number of show causes; students’ written show cause responses; weighted average mark at last show cause or graduation; whether they graduated and were a registered pharmacist; and, the number of years they spent studying the degree. Descriptive studies were used to analyse student characteristics using SPSS software, and student self-reported reasons for poor performance were analysed reflexively using thematic analysis procedures using NVivo.

Results

This study included 164 pharmacy students enrolled in a BPharm (79.3%, n = 130), BPharmMgmt (1.2%, n = 2), or MPharm (19.5%, n = 32). Of the students, 54% (n = 88) were men, 81% (n = 133) were domestic students, 15% (n = 24) transferred from another degree program, and 38% (n = 62) graduated from the course. Show cause students were less likely to graduate if they transferred from another degree program (P = 0.0002) or failed more than three units of study (UoS; P < 0.0001). The most commonly failed UoS were related to organic or pharmaceutical chemistry, and the top student self-reported reasons for poor performance was stress/anxiety, physical health, and depression.

Conclusion

Pharmacy schools should aim to address student foundational knowledge in chemistry, identify at-risk students early using pre-subject testing, and provide better services to address student mental health.
The feedback dilemma in medical education: insights from medical residents’ perspectives
Authors: Shafian Sara , Ilaghi Mehran , Shahsavani Yasamin , Okhovati Maryam , Soltanizadeh Adel , Aflatoonian Sarah , Karamoozian Ali
Published: April 2024

Background

Feedback is a critical component of the learning process in a clinical setting. This study aims to explore medical residents’ perspectives on feedback delivery and identify potential barriers to feedback-seeking in clinical training.

Methods

This cross-sectional study involved 180 medical residents across seventeen specialties. We employed the validated Residency Education Feedback Level Evaluation in Clinical Training (REFLECT) tool to assess residents’ perspectives on their attitude toward feedback, quality of feedback, perceived importance, and reaction to feedback. Additionally, we explored barriers to feedback-seeking behavior among medical residents.

Results

The majority of medical residents held positive attitudes toward feedback. They agreed that feedback improves their clinical performance (77.7%), professional behavior (67.2%), and academic motivation (56.7%), while also influencing them to become a better specialist in their future career (72.8%). However, the study revealed critical deficiencies in the feedback process. Only 25.6% of residents reported receiving regular feedback and less than half reported that feedback was consistently delivered at suitable times and locations, was sufficiently clear or included actionable plans for improvement. A minority (32.2%) agreed that faculty had sufficient skills to deliver feedback effectively. Moreover, peer-to-peer feedback appeared to be a primary source of feedback among residents. Negative feedback, though necessary, often triggered feelings of stress, embarrassment, or humiliation. Notably, there were no significant differences in feedback perceptions among different specialties. The absence of a feedback-seeking culture emerged as a central barrier to feedback-seeking behavior in the clinical setting.

Conclusions

Establishing shared expectations and promoting a culture of feedback-seeking could bridge the gap between residents’ perceptions and faculty feedback delivery. Furthermore, recognizing the role of senior and peer residents as valuable feedback sources can contribute to more effective feedback processes in clinical training, ultimately benefiting resident development and patient care.
Two-year follow-up of a clustered randomised controlled trial of a multicomponent general practice intervention for people at risk of poor health outcomes
Authors: Reed Richard L. , Roeger Leigh , Kaambwa Billingsley
Published: April 2024

Background

This study was a two-year follow-up evaluation of health service use and the cost-effectiveness of a multicomponent general practice intervention targeted at people at high risk of poor health outcomes.

Methods

A two-year follow-up study of a clustered randomised controlled trial was conducted in South Australia during 2018–19, recruiting 1044 patients from three cohorts: children; adults (aged 18–64 years with two or more chronic diseases); and older adults (aged ≥ 65 years). Intervention group practices (n = 10) provided a multicomponent general practice intervention for 12 months. The intervention comprised patient enrolment to a preferred general practitioner (GP), access to longer GP appointments and timely general practice follow-up after episodes of hospital care. Health service outcomes included hospital use, specialist services and pharmaceuticals. The economic evaluation was based on quality-adjusted life years (QALYs) calculated from EuroQoL 5 dimensions, 5 level utility scores and used an A$50,000 per QALY gained threshold for determining cost-effectiveness.

Results

Over the two years, there were no statistically significant intervention effects for health service use. In the total sample, the mean total cost per patient was greater for the intervention than control group, but the number of QALYs gained in the intervention group was higher. The estimated incremental cost-effectiveness ratio (ICER) was A$18,211 per QALY gained, which is lower than the A$50,000 per QALY gained threshold used in Australia. However, the intervention's cost-effectiveness was shown to differ by cohort. For the adult cohort, the intervention was associated with higher costs and lower QALYs gained (vs the total cohort) and was not cost-effective. For the older adults cohort, the intervention was associated with lower costs (A$540 per patient), due primarily to lower hospital costs, and was more effective than usual care.

Conclusions

The positive cost-effectiveness results from the 24-month follow-up warrant replication in a study appropriately powered for outcomes such as hospital use, with an intervention period of at least two years, and targeted to older people at high risk of poor health outcomes.
A scoping review of continuous quality improvement in healthcare system: conceptualization, models and tools, barriers and facilitators, and impact
Authors: Endalamaw Aklilu , Khatri Resham B , Mengistu Tesfaye Setegn , Erku Daniel , Wolka Eskinder , Zewdie Anteneh , Assefa Yibeltal
Published: April 2024

Background

The growing adoption of continuous quality improvement (CQI) initiatives in healthcare has generated a surge in research interest to gain a deeper understanding of CQI. However, comprehensive evidence regarding the diverse facets of CQI in healthcare has been limited. Our review sought to comprehensively grasp the conceptualization and principles of CQI, explore existing models and tools, analyze barriers and facilitators, and investigate its overall impacts.

Methods

This qualitative scoping review was conducted using Arksey and O’Malley’s methodological framework. We searched articles in PubMed, Web of Science, Scopus, and EMBASE databases. In addition, we accessed articles from Google Scholar. We used mixed-method analysis, including qualitative content analysis and quantitative descriptive for quantitative findings to summarize findings and PRISMA extension for scoping reviews (PRISMA-ScR) framework to report the overall works.

Results

A total of 87 articles, which covered 14 CQI models, were included in the review. While 19 tools were used for CQI models and initiatives, Plan-Do-Study/Check-Act cycle was the commonly employed model to understand the CQI implementation process. The main reported purposes of using CQI, as its positive impact, are to improve the structure of the health system (e.g., leadership, health workforce, health technology use, supplies, and costs), enhance healthcare delivery processes and outputs (e.g., care coordination and linkages, satisfaction, accessibility, continuity of care, safety, and efficiency), and improve treatment outcome (reduce morbidity and mortality). The implementation of CQI is not without challenges. There are cultural (i.e., resistance/reluctance to quality-focused culture and fear of blame or punishment), technical, structural (related to organizational structure, processes, and systems), and strategic (inadequate planning and inappropriate goals) related barriers that were commonly reported during the implementation of CQI.

Conclusions

Implementing CQI initiatives necessitates thoroughly comprehending key principles such as teamwork and timeline. To effectively address challenges, it’s crucial to identify obstacles and implement optimal interventions proactively. Healthcare professionals and leaders need to be mentally equipped and cognizant of the significant role CQI initiatives play in achieving purposes for quality of care.
A longitudinal cohort study on the use of health and care services by older adults living at home with/without dementia before and during the COVID-19 pandemic: the HUNT study
Authors: Ibsen Tanja Louise , Strand Bjørn Heine , Bergh Sverre , Livingston Gill , Lurås Hilde , Mamelund Svenn-Erik , Voshaar Richard Oude , Rokstad Anne Marie Mork , Thingstad Pernille , Gerritsen Debby , Selbæk Geir
Published: April 2024

Background

Older adults and people with dementia were anticipated to be particularly unable to use health and care services during the lockdown period following the COVID-19 pandemic. To better prepare for future pandemics, we aimed to investigate whether the use of health and care services changed during the pandemic and whether those at older ages and/or dementia experienced a higher degree of change than that observed by their counterparts.

Methods

Data from the Norwegian Trøndelag Health Study (HUNT4 70 + , 2017–2019) were linked to two national health registries that have individual-level data on the use of primary and specialist health and care services. A multilevel mixed-effects linear regression model was used to calculate changes in the use of services from 18 months before the lockdown, (12 March 2020) to 18 months after the lockdown.

Results

The study sample included 10,607 participants, 54% were women and 11% had dementia. The mean age was 76 years (SD: 5.7, range: 68–102 years). A decrease in primary health and care service use, except for contact with general practitioners (GPs), was observed during the lockdown period for people with dementia (p < 0.001) and those aged ≥ 80 years without dementia (p = 0.006), compared to the 6-month period before the lockdown. The use of specialist health services decreased during the lockdown period for all groups (p ≤ 0.011), except for those aged < 80 years with dementia. Service use reached levels comparable to pre-pandemic data within one year after the lockdown.

Conclusion

Older adults experienced an immediate reduction in the use of health and care services, other than GP contacts, during the first wave of the COVID-19 pandemic. Within primary care services, people with dementia demonstrated a more pronounced reduction than that observed in people without dementia; otherwise, the variations related to age and dementia status were small. Both groups returned to services levels similar to those during the pre-pandemic period within one year after the lockdown. The increase in GP contacts may indicate a need to reallocate resources to primary health services during future pandemics.

Trial registration

The study is registered at ClinicalTrials.gov, with the identification number NCT 04792086.
“It’s hard to say anything definitive about what severity really is”: lay conceptualisations of severity in a healthcare context
Authors: Stenmarck Mille Sofie , Whitehurst David GT , Lurås Hilde , Rugkåsa Jorun
Published: April 2024

Background

Demand for healthcare outweighs available resources, making priority setting a critical issue. ‘Severity’ is a priority-setting criterion in many healthcare systems, including in Norway, Sweden, the Netherlands, and the United Kingdom. However, there is a lack of consensus on what severity means in a healthcare context, both in the academic literature and in policy. Further, while public preference elicitation studies demonstrate support for severity as a relevant concern in priority setting, there is a paucity of research on what severity is taken to mean for the public. The purpose of this study is to explore how severity is conceptualised by members of the general public.

Methods

Semi-structured group interviews were conducted from February to July 2021 with members of the Norwegian adult public (n = 59). These were transcribed verbatim and subjected to thematic analysis, incorporating inductive and deductive elements.

Results

Through the analysis we arrived at three interrelated main themes.Severity as subjective experienceincluded perceptions of severity as inherently subjective and personal. Emphasis was on the individual’s unique insight into their illness, and there was a concern that the assessment of severity should be fair for the individual. The second theme,Severity as objective fact, included perceptions of severity as something determined by objective criteria, so that a severe condition is equally severe for any person. Here, there was a concern for determining severity fairly within and across patient groups. The third theme,Severity as situation dependent, included perceptions of severity centered on second-order effects of illness. These included effects on the individual, such as their ability to work and enjoy their hobbies, effects on those surrounding the patient, such as next of kin, and effects at a societal level, such as production loss. We also identified a concern for determining severity fairly at a societal level.

Conclusions

Our findings suggest that severity is a polyvalent notion with different meanings attached to it. There seems to be a dissonance between lay conceptualisations of severity and policy operationalisations of the term, which may lead to miscommunications between members of the public and policymakers.
Prediction of blood–brain barrier penetrating peptides based on data augmentation with Augur
Authors: Gu Zhi-Feng , Hao Yu-Duo , Wang Tian-Yu , Cai Pei-Ling , Zhang Yang , Deng Ke-Jun , Lin Hao , Lv Hao
Published: April 2024

Background

The blood–brain barrier serves as a critical interface between the bloodstream and brain tissue, mainly composed of pericytes, neurons, endothelial cells, and tightly connected basal membranes. It plays a pivotal role in safeguarding brain from harmful substances, thus protecting the integrity of the nervous system and preserving overall brain homeostasis. However, this remarkable selective transmission also poses a formidable challenge in the realm of central nervous system diseases treatment, hindering the delivery of large-molecule drugs into the brain. In response to this challenge, many researchers have devoted themselves to developing drug delivery systems capable of breaching the blood–brain barrier. Among these, blood–brain barrier penetrating peptides have emerged as promising candidates. These peptides had the advantages of high biosafety, ease of synthesis, and exceptional penetration efficiency, making them an effective drug delivery solution. While previous studies have developed a few prediction models for blood–brain barrier penetrating peptides, their performance has often been hampered by issue of limited positive data.

Results

In this study, we present Augur, a novel prediction model using borderline-SMOTE-based data augmentation and machine learning. we extract highly interpretable physicochemical properties of blood–brain barrier penetrating peptides while solving the issues of small sample size and imbalance of positive and negative samples. Experimental results demonstrate the superior prediction performance of Augur with an AUC value of 0.932 on the training set and 0.931 on the independent test set.

Conclusions

This newly developed Augur model demonstrates superior performance in predicting blood–brain barrier penetrating peptides, offering valuable insights for drug development targeting neurological disorders. This breakthrough may enhance the efficiency of peptide-based drug discovery and pave the way for innovative treatment strategies for central nervous system diseases.
Anti-PD-1 antibody in combination with radiotherapy as first-line therapy for unresectable intrahepatic cholangiocarcinoma
Authors: Zhu Meiyan , Jin Meng , Zhao Xiao , Shen Shunli , Chen Yihan , Xiao Han , Wei Guangyan , He Qiang , Li Bin , Peng Zhenwei
Published: April 2024

Background

Unresectable intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis despite treatment with standard combination chemotherapy. We aimed to evaluate the efficacy and safety of radiotherapy in combination with an anti-PD-1 antibody in unresectable iCCA without distant metastases.

Methods

In this phase II study, patients with histopathologically confirmed unresectable primary or postoperative recurrent iCCA without distant metastases were enrolled. Patients received external radiotherapy with a dose of ≥45 Gy (2-2.5 Gy per fraction), followed by anti-PD-1 immunotherapy (camrelizumab 200 mg once, every 3 weeks) initiated within 7 days after completion of radiotherapy as first-line therapy. The primary endpoint was 1-year progression-free survival (PFS) rate. The secondary end points included safety, objective response rate (ORR), disease control rate (DCR), and overall survival (OS).

Results

From December 2019 to March 2021, 36 patients completed radiotherapy and at least one cycle of immunotherapy and were included in efficacy and safety analyses. The median follow-up was 19.0 months (IQR 12.0-24.0), and the one-year PFS rate was 44.4% (95% CI, 30.8-64.0). The median PFS was 12.0 months (95% CI, 7.5-not estimable); the median OS was 22.0 months (95% CI, 15.0-not estimable). The ORR was 61.1% and the DCR was 86.1%. Seventeen of 36 (47.2%) patients experienced treatment-related adverse effects (AEs) of any grade. The most common AE was reactive cutaneous capillary endothelial proliferation (25.0%). Five (13.9%) patients experienced grade ≥3 treatment-related AEs, including decreased lymphocyte (5.6%), bullous dermatitis (2.8%), decreased platelet count (2.8%), and deep-vein thrombosis (2.8%).

Conclusions

External radiotherapy plus camrelizumab, as first-line therapy, met its primary endpoint and showed antitumor activity and low toxicity levels in patients with unresectable iCCA without distant metastases, warranting further investigation.

Trial registration

NCT03898895. Registered 2 April 2019.
Prevalence and differences in the co-administration of drugs known to interact: an analysis of three distinct and large populations
Authors: Sánchez-Valle Jon , Correia Rion Brattig , Camacho-Artacho Marta , Lepore Rosalba , Mattos Mauro M. , Rocha Luis M. , Valencia Alfonso
Published: April 2024

Background

The co-administration of drugs known to interact greatly impacts morbidity, mortality, and health economics. This study aims to examine the drug–drug interaction (DDI) phenomenon with a large-scale longitudinal analysis of age and gender differences found in drug administration data from three distinct healthcare systems.

Methods

This study analyzes drug administrations from population-wide electronic health records in Blumenau (Brazil; 133 K individuals), Catalonia (Spain; 5.5 M individuals), and Indianapolis (USA; 264 K individuals). The stratified prevalences of DDI for multiple severity levels per patient gender and age at the time of administration are computed, and null models are used to estimate the expected impact of polypharmacy on DDI prevalence. Finally, to study actionable strategies to reduce DDI prevalence, alternative polypharmacy regimens using drugs with fewer known interactions are simulated.

Results

A large prevalence of co-administration of drugs known to interact is found in all populations, affecting 12.51%, 12.12%, and 10.06% of individuals in Blumenau, Indianapolis, and Catalonia, respectively. Despite very different healthcare systems and drug availability, the increasing prevalence of DDI as patients age is very similar across all three populations and is not explained solely by higher co-administration rates in the elderly. In general, the prevalence of DDI is significantly higher in women — with the exception of men over 50 years old in Indianapolis. Finally, we show that using proton pump inhibitor alternatives to omeprazole (the drug involved in more co-administrations in Catalonia and Blumenau), the proportion of patients that are administered known DDI can be reduced by up to 21% in both Blumenau and Catalonia and 2% in Indianapolis.

Conclusions

DDI administration has a high incidence in society, regardless of geographic, population, and healthcare management differences. Although DDI prevalence increases with age, our analysis points to a complex phenomenon that is much more prevalent than expected, suggesting comorbidities as key drivers of the increase. Furthermore, the gender differences observed in most age groups across populations are concerning in regard to gender equity in healthcare. Finally, our study exemplifies how electronic health records’ analysis can lead to actionable interventions that significantly reduce the administration of known DDI and its associated human and economic costs.
Undiagnosed type 2 diabetes is common – intensified screening of established risk groups is imperative in Sweden: the SDPP cohort
Authors: Gudjonsdottir Hrafnhildur , Tynelius Per , Stattin Nouha Saleh , Méndez Diego Yacamán , Lager Anton , Brynedal Boel
Published: April 2024

Background

Undiagnosed type 2 diabetes (T2D) is a global problem. Current strategies for diagnosis in Sweden include screening individuals within primary healthcare who are of high risk, such as those with hypertension, obesity, prediabetes, family history of diabetes, or those who smoke daily. In this study, we aimed to estimate the proportion of individuals with undiagnosed T2D in Stockholm County and factors associated with T2D being diagnosed by healthcare. This information could improve strategies for detection.

Methods

We used data from the Stockholm Diabetes Prevention Programme (SDPP) cohort together with information from national and regional registers. Individuals without T2D aged 35–56 years at baseline were followed up after two ten-year periods. The proportion of diagnosed T2D was based on register information for 7664 individuals during period 1 and for 5148 during period 2. Undiagnosed T2D was assessed by oral glucose tolerance tests at the end of each period. With logistic regression, we analysed factors associated with being diagnosed among individuals with T2D.

Results

At the end of the first period, the proportion of individuals with T2D who had been diagnosed with T2D or not was similar (54.0% undiagnosed). At the end of the second period, the proportion of individuals with T2D was generally higher, but they were less likely to be undiagnosed (43.5%). The likelihood of being diagnosed was in adjusted analyses associated with overweight (OR=1.85; 95% CI 1.22–2.80), obesity (OR=2.73; 95% CI 1.76–4.23), higher fasting blood glucose (OR=2.11; 95% CI 1.67–2.66), and self-estimated poor general health (OR=2.42; 95% CI 1.07–5.45). Socioeconomic factors were not associated with being diagnosed among individuals with T2D. Most individuals (>71%) who developed T2D belonged to risk groups defined by having at least two of the prominent risk factors obesity, hypertension, daily smoking, prediabetes, or family history of T2D, including individuals with T2D who had not been diagnosed by healthcare.

Conclusions

Nearly half of individuals who develop T2D during 10 years in Stockholm County are undiagnosed, emphasizing a need for intensified screening of T2D within primary healthcare. Screening can be targeted to individuals who have at least two prominent risk factors.
Applications of peptides in nanosystems for diagnosing and managing bacterial sepsis
Authors: Gafar Mohammed A. , Omolo Calvin A. , Elhassan Eman , Ibrahim Usri H. , Govender Thirumala
Published: April 2024

Sepsis represents a critical medical condition stemming from an imbalanced host immune response to infections, which is linked to a significant burden of disease. Despite substantial efforts in laboratory and clinical research, sepsis remains a prominent contributor to mortality worldwide. Nanotechnology presents innovative opportunities for the advancement of sepsis diagnosis and treatment. Due to their unique properties, including diversity, ease of synthesis, biocompatibility, high specificity, and excellent pharmacological efficacy, peptides hold great potential as part of nanotechnology approaches against sepsis. Herein, we present a comprehensive and up-to-date review of the applications of peptides in nanosystems for combating sepsis, with the potential to expedite diagnosis and enhance management outcomes. Firstly, sepsis pathophysiology, antisepsis drug targets, current modalities in management and diagnosis with their limitations, and the potential of peptides to advance the diagnosis and management of sepsis have been adequately addressed. The applications have been organized into diagnostic or managing applications, with the last one being further sub-organized into nano-delivered bioactive peptides with antimicrobial or anti-inflammatory activity, peptides as targeting moieties on the surface of nanosystems against sepsis, and peptides as nanocarriers for antisepsis agents. The studies have been grouped thematically and discussed, emphasizing the constructed nanosystem, physicochemical properties, and peptide-imparted enhancement in diagnostic and therapeutic efficacy. The strengths, limitations, and research gaps in each section have been elaborated. Finally, current challenges and potential future paths to enhance the use of peptides in nanosystems for combating sepsis have been deliberately spotlighted. This review reaffirms peptides' potential as promising biomaterials within nanotechnology strategies aimed at improving sepsis diagnosis and management.

Graphical Abstract
Ageing of Plasmodium falciparum malaria sporozoites alters their motility, infectivity and reduces immune activation in vitro
Authors: van Schuijlenburg Roos , Azargoshasb Samaneh , de Korne Clarize M. , Sijtsma Jeroen C. , Bezemer Sascha , van der Ham Alwin J. , Baalbergen Els , Geurten Fiona , de Bes-Roeleveld Laura M. , Chevalley-Maurel Severine C. , van Oosterom Matthias N. , van Leeuwen Fijs W. B. , Franke-Fayard Blandine , Roestenberg Meta
Published: April 2024

Background

Sporozoites (SPZ), the infective form of Plasmodium falciparum malaria, can be inoculated into the human host skin by Anopheline mosquitoes. These SPZ migrate at approximately 1 µm/s to find a blood vessel and travel to the liver where they infect hepatocytes and multiply. In the skin they are still low in number (50–100 SPZ) and vulnerable to immune attack by antibodies and skin macrophages. This is why whole SPZ and SPZ proteins are used as the basis for most malaria vaccines currently deployed and undergoing late clinical testing. Mosquitoes typically inoculate SPZ into a human host between 14 and 25 days after their previous infective blood meal. However, it is unknown whether residing time within the mosquito affects SPZ condition, infectivity or immunogenicity. This study aimed to unravel how the age of P. falciparum SPZ in salivary glands (14, 17, or 20 days post blood meal) affects their infectivity and the ensuing immune responses.

Methods

SPZ numbers, viability by live/dead staining, motility using dedicated sporozoite motility orienting and organizing tool software (SMOOT), and infectivity of HC-04.j7 liver cells at 14, 17 and 20 days after mosquito feeding have been investigated. In vitro co-culture assays with SPZ stimulated monocyte-derived macrophages (MoMɸ) and CD8+ T-cells, analysed by flow cytometry, were used to investigate immune responses.

Results

SPZ age did not result in different SPZ numbers or viability. However, a markedly different motility pattern, whereby motility decreased from 89% at day 14 to 80% at day 17 and 71% at day 20 was observed (p ≤ 0.0001). Similarly, infectivity of day 20 SPZ dropped to ~ 50% compared with day 14 SPZ (p = 0.004). MoMɸ were better able to take up day 14 SPZ than day 20 SPZ (from 7.6% to 4.1%, p = 0.03) and displayed an increased expression of pro-inflammatory CD80, IL-6 (p = 0.005), regulatory markers PDL1 (p = 0.02), IL-10 (p = 0.009) and cytokines upon phagocytosis of younger SPZ. Interestingly, co-culture of these cells with CD8+ T-cells revealed a decreased expression of activation marker CD137 and cytokine IFNγ compared to their day 20 counterparts. These findings suggest that older (day 17–20) P. falciparum SPZ are less infectious and have decreased immune regulatory potential.

Conclusion

Overall, this data is a first step in enhancing the understanding of how mosquito residing time affects P. falciparum SPZ and could impact the understanding of the P. falciparum infectious reservoir and the potency of whole SPZ vaccines.
National strategies for knowledge translation in health policy-making: A scoping review of grey literature
Authors: Babarczy Balázs , Scarlett Julia , Sharma Tarang , Gaál Péter , Szécsényi-Nagy Balázs , Kuchenmüller Tanja
Published: April 2024

Background and objectives

Without strategic actions in its support, the translation of scientific research evidence into health policy is often absent or delayed. This review systematically maps and assesses national-level strategic documents in the field of knowledge translation (KT) for health policy, and develops a practical template that can support Evidence-informed Policy Network (EVIPNet) Europe countries in producing national strategies for evidence-informed policy-making.

Methods

Websites of organizations with strategic responsibilities in KT were electronically searched, on the basis of pre-defined criteria, in July–August 2017, and an updated search was carried out in April–June 2021. We included national strategies or elements of national strategies that dealt with KT activities, as well as similar strategies of individual institutions with a national policy focus. Two reviewers screened the strategies for inclusion. Data were analysed using qualitative content analysis.

Results

A total of 65 unique documents were identified, of which 17 were eligible and analysed for their structure and content. Of the 17, 1 document was a national health KT action plan and 6 documents were institution-level KT strategies. The remaining 10 strategies, which were also included were 2 national health strategies, 5 national health research strategies and 3 national KT strategies (not specific to the field of health alone). In all, 13 structural elements and 7 major themes of health policy KT strategies were identified from the included documents.

Conclusion

KT in health policy, as emerged from the national strategies that our mapping identified, is based on the production and accessibility of policy-relevant research, its packaging for policy-making and the activities related to knowledge exchange. KT strategies may play different roles in the complex and context-specific process of policy-making. Our findings show that the main ideas of health-specific evidence-informed policy literature appear in these strategies, but their effectiveness depends on the way stakeholders use them. Specific knowledge-brokering institutions and organizational capacity, advocacy about the use of evidence, and close collaboration and co-decision-making with key stakeholders are essential in furthering the policy uptake of research results.
Effectiveness of workplace interventions with digital elements to reduce sedentary behaviours in office employees: a systematic review and meta-analysis
Authors: Parés-Salomón Iris , Señé-Mir Anna M. , Martín-Bozas Fernando , Loef Bette , Coffey Alan , Dowd Kieran P. , Jabardo-Camprubí Guillem , Proper Karin I. , Puig-Ribera Anna , Bort-Roig Judit
Published: April 2024

Background

Digital interventions are potential tools for reducing and limiting occupational sedentary behaviour (SB) in sedentary desk-based jobs. Given the harmful effects of sitting too much and sitting for too long while working, the aim of this systematic review and meta-analysis was to examine the effectiveness of workplace interventions, that incorporated digital elements, to reduce the time spent in SB in office workers.

Methods

Randomised control trials that evaluated the implementation of workplace interventions that incorporated digital elements for breaking and limiting SB among desk-based jobs were identified by literature searches in six electronic databases (PubMed, Web of Science, Scopus, CINAHL, PsycINFO and PEDro) published up to 2023. Studies were included if total and/or occupational SB were assessed. Only studies that reported pre- and postintervention mean differences and standard deviations or standard errors for both intervention arms were used for the meta-analysis. The meta-analysis was conducted using Review Manager 5 (RevMan 5; Cochrane Collaboration, Oxford, UK). Risk of bias was assessed using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields QUALSYST tool.

Results

Nineteen studies were included in the systematic review. The most employed digital elements were information delivery and mediated organisational support and social influences. Multicomponent, information, and counselling interventions measuring total and/or occupational/nonoccupational SB time by self-report or via device-based measures were reported. Multicomponent interventions were the most represented. Eleven studies were included in the meta-analysis, which presented a reduction of 29.9 (95% CI: -45.2, -14.5) min/8 h workday in SB (overall effect: Z = 3.81).

Conclusions

Multicomponent interventions, using a wide range of digital features, have demonstrated effectiveness in reducing time spent in SB at the workplace among desk-based employees. However, due to hybrid work (i.e., work in the office and home) being a customary mode of work for many employees, it is important for future studies to assess the feasibility and effectiveness of these interventions in the evolving work landscape.

Trial registration

The review protocol was registered in the Prospero database (CRD42022377366).
Stability and integrity of self-assembled bovine parvovirus virus‑like particles (BPV‑VLPs) of VP2 and combination of VP1VP2 assisted by baculovirus-insect cell expression: a potential logistical platform for vaccine deployment
Authors: Wubshet Ashenafi Kiros , Li Guo-xiu , Li Qian , Dai Jun-Fei , Ding Yao-Zhong , Zhou Luoyi , Qu Min , Wang Yang , Ma Zhongyuan , Werid Gebremeskel Mamu , Abera Birhanu Hadush , Kebede Asmelash Tassew , Sun Yuefeng , Yin Xiangping , Liu Yongsheng , Jie Zhang
Published: April 2024

Background

Bovine parvovirus (BPV) is an autonomous DNA virus with a smaller molecular size and subtle differences in its structural proteins, unlike other animal parvoviruses. More importantly, this virus has the potential to produce visible to silent economic catastrophes in the livestock business, despite receiving very little attention. Parvoviral virus-like particles (VLPs) as vaccines and as logistical platforms for vaccine deployment are well studied. However, no single experimental report on the role of VP1 in the assembly and stability of BPV-VLPs is available. Furthermore, the self-assembly, integrity and stability of the VLPs of recombinant BPV VP2 in comparison to VP1 VP2 Cap proteins using any expression method has not been studied previously. In this study, we experimentally evaluated the self-assembling ability with which BPV virus-like particles (VLPs) could be synthesized from a single structural protein (VP2) and by integrating both VP2 and VP1 amino acid sequences.

Methods

In silico and experimental cloning methods were carried out. His-tagged and without-His-tag VP2 and V1VP2-encoding amino acid sequences were cloned and inserted into pFastbacdual, and insect cell-generated recombinant protein was evaluated by SDS‒PAGE and western blot. Period of infectivity and expression level were determined by IFA. The integrity and stability of the BPV VLPs were evaluated by transmission electron microscopy. The secondary structure of the BPV VLPs from both VP2 and V1VP2 was analyzed by circular dichroism.

Results

Our findings show that VP2 alone was equally expressed and purified into detectable proteins, and the stability at different temperatures and pH values was not appreciably different between the two kinds of VLPs. Furthermore, BPV-VP2 VLPs were praised for their greater purity and integrity than BPV-VP1VP2 VLPs, as indicated by SDS‒PAGE. Therefore, our research demonstrates that the function of VP1 has no bearing on the stability or integrity of BPV-VLPs.

Conclusions

In summary, incredible physiochemically stable BPV VP2-derived VLPs have been found to be promising candidates for the development of multivalent vaccines and immunodiagnostic kits against enteric viruses and to carry heterogeneous epitopes for various economically important livestock diseases.
Computational analysis of affinity dynamics between the variants of SARS-CoV-2 spike protein (RBD) and human ACE-2 receptor
Authors: Sultana Nishad , Nagesha S. N. , Reddy C. N. Lakshminarayana , Ramesh B. N. , Shyamalamma S. , Shashidhara K. S. , Satish K. M. , Pradeep C. , Vidyadhar G. D
Published: April 2024

The novel coronavirus SARS-CoV-2 resulted in a significant worldwide health emergency known as the COVID-19 pandemic. This crisis has been marked by the widespread of various variants, with certain ones causing notable apprehension. In this study, we harnessed computational techniques to scrutinize these Variants of Concern (VOCs), including various Omicron subvariants. Our approach involved the use of protein structure prediction algorithms and molecular docking techniques, we have investigated the effects of mutations within the Receptor Binding Domain (RBD) of SARS-CoV-2 and how these mutations influence its interactions with the human angiotensin-converting enzyme 2 (hACE-2) receptor. Further we have predicted the structural alterations in the RBD of naturally occurring SARS-CoV-2 variants using the tr-Rosetta algorithm. Subsequent docking and binding analysis employing HADDOCK and PRODIGY illuminated crucial interactions occurring at the Receptor-Binding Motif (RBM). Our findings revealed a hierarchy of increased binding affinity between the human ACE2 receptor and the various RBDs, in the order of wild type (Wuhan-strain) < Beta < Alpha < Gamma < Omicron-B.1.1.529 < Delta < Omicron-BA.2.12.1 < Omicron-BA.5.2.1 < Omicron-BA.1.1. Notably, Omicron-BA.1.1 demonstrated the highest binding affinity of -17.4 kcal mol−1 to the hACE2 receptor when compared to all the mutant complexes. Additionally, our examination indicated that mutations occurring in active residues of the Receptor Binding Domain (RBD) consistently improved the binding affinity and intermolecular interactions in all mutant complexes. Analysis of the differences among variants has laid a foundation for the structure-based drug design targeting the RBD region of SARS-CoV-2.
Brief interventions 2.0: a new agenda for alcohol policy, practice and research
Authors: Stewart Duncan , Madden Mary , McCambridge Jim
Published: April 2024

Background

Alcohol problems are increasing across the world and becoming more complex. Limitations to international evidence and practice mean that the screening and brief intervention paradigm forged in the 1980s is no longer fit for the purpose of informing how conversations about alcohol should take place in healthcare and other services. A new paradigm for brief interventions has been called for.

Brief interventions 2.0

We must start with a re-appraisal of the roles of alcohol in society now and the damage it does to individual and population health. Industry marketing and older unresolved ideas about alcohol continue to impede honest and thoughtful conversations and perpetuate stigma, stereotypes, and outright fictions. This makes it harder to think about and talk about how alcohol affects health, well-being, and other aspects of life, and how we as a society should respond. To progress, brief interventions should not be restricted only to the self-regulation of one’s own drinking. Content can be orientated to the properties of the drug itself and the overlooked problems it causes, the policy issues and the politics of a powerful globalised industry. This entails challenging and reframing stigmatising notions of alcohol problems, and incorporating wider alcohol policy measures and issues that are relevant to how people think about their own and others' drinking. We draw on recent empirical work to examine the implications of this agenda for practitioners and for changing the public conversation on alcohol.

Conclusion

Against a backdrop of continued financial pressures on health service delivery, this analysis provokes debate and invites new thinking on alcohol. We suggest that the case for advancing brief interventions version 2.0 is both compelling and urgent.
Clinical values of different specimen preparation methods for the diagnosis of lung cancer by EBUS-TBNA
Authors: Wang Hansheng , Wang Jiankun , Liu Yan , Wang Yunyun , Zhou Yanhui , Yu Dan , You Hui , Ren Tao , Tang Yijun , Wang Meifang
Published: April 2024

Background and objective

EBUS-TBNA has emerged as an important minimally invasive procedure for the diagnosis and staging of lung cancer. Our objective was to evaluate the effect of different specimen preparation from aspirates on the diagnosis of lung cancer.

Methods

181 consecutive patients with known or suspected lung cancer accompanied by hilar / mediastinal lymphadenopathy underwent EBUS-TBNA from January 2019 to December 2022. Specimens obtained by EBUS-TBNA were processed by three methods: Traditional smear cytology of aspirates (TSC), liquid-based cytology of aspirates (LBC) and histopathology of core biopsies.

Results

EBUS-TBNA was performed in 181 patients on 213 lymph nodes, the total positive rate of the combination of three specimen preparation methods was 80.7%. The diagnostic positive rate of histopathology was 72.3%, TSC was 68.1%, and LBC was 65.3%, no significant differences was observed (p = 0.29); however, statistically significant difference was noted between the combination of three preparation methods and any single specimen preparation methods (p = 0.002). The diagnostic sensitivity of histopathology combined with TSC and histopathology combined with LBC were 96.5 and 94.8%, the specificity was 95.0% and 97.5%, the PPV was 98.8% and 99.4%, the NPV was 86.4% and 81.2%, the diagnostic accuracy was 96.2% and 95.3%, respectively; The sensitivity and accuracy of above methods were higher than that of single specimen preparation, but lower than that of combination of three preparation methods.

Conclusion

When EBUS-TBNA is used for the diagnosis and staging of lung cancer, histopathology combined with TSC can achieve enough diagnostic efficiency and better cost-effectiveness.
Stepwise transvenous lead extraction due to pacemaker pocket infection following lactational mastitis complicated with breast abscess
Authors: Poposka Lidija , Risteski Dejan , Cvetkovski Dimitar , Pocesta Bekim , Janusevski Filip , Zimbakov Zhan , Trajkov Ivan , Stefanovski Dime , Logar Mateja , Ksela Jus
Published: April 2024

Background

Lactational mastitis is a common painful and debilitating inflammation of breast tissue, generally treated conservatively or with pus puncture in case of breast abscess. However, treating mastitis in patients with implantable surgical material located in the affected breast region can be extremely challenging. We present an unusual case of lactational mastitis complicated by pacemaker pocket infection in a breastfeeding mother.

Case presentation

A 35-year-old pacemaker-dependent female developed lactational mastitis seven weeks postpartum. Initially, the condition was treated conservatively with analgesics and antibiotics. After abscess formation, pus was aspirated using fine-needle aspiration technique. Four weeks after mastitis resolution, pacemaker pocket infection developed. According to current cardiovascular implantable electronic device infection treatment guidelines a complete surgical extraction of the entire electronic system, followed by targeted antibiotic treatment and reimplantation of a new device after infection resolution, was recommended. However, after thorough discussion with the young woman and her family and after detailed review of surgery-related risks, she declined a potentially high-risk surgical procedure. Thus, only the pulse generator was explanted; pacing leads positioned in the sub-pectoral pocket; new pacemaker implanted on the contralateral side and broad-spectrum antibiotic therapy continued for six weeks. After breastfeeding cessation, and with chronic fistula development at the primary pacemaker implantation site, the possibility of delayed surgical intervention including complete extraction of retained pacemaker leads was again thoroughly discussed with her. After thoughtful consideration the woman consented to the proposed treatment strategy. A surgical procedure including transvenous lead extraction through the primary implantation venous entry site, using hand-powered bidirectional rotational sheaths, was successfully performed, removing all retained leads through the left subclavian venous entry site, and leaving the fully functional and clinically uninfected pacemaker on the contralateral site intact.

Conclusion

Although patients’ decisions for delayed extraction in a case of cardiovascular implantable electronic device infection should be discouraged by attending physicians and members of interdisciplinary teams, our case shows that a stepwise treatment strategy may be successful as a bailout clinical scenario in patients with specific requests, demands and / or clinical needs.