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Diabetes mellitus is a major risk factor for heart disease (heart attack, angina, and heart failure), stroke, and hypertension, which shorten the average life expectancy. The main objective of this study was to describe the prevalence of heart disease, hypertension, and stroke among Canadians with diabetes compared to those without diabetes in the Canadian general population aged 12 years and over. It also estimated the strength of association between diabetes, heart disease, hypertension, and other factors such as age, gender, cigarette smoking, alcohol drinking, education status, body mass index (BMI), and other socioeconomic factors. Descriptive statistics were used initially to estimate the prevalence of related comorbidities by age and gender. Logistic regression was then employed to determine the potential strength of association between various effects. Data included 127,610 individuals who participated in the 2.1 cycles of the Canadian Community Health Survey (CCHS) in 2002—2003. The prevalence of self-reported hypertension, heart disease, and stroke among individuals with diabetes were 51.9, 21.7, and 4.8%, respectively. By comparison, prevalence among those without diabetes was 12.7, 4.2, and 0.9%. Adjusted Odds Ratios (OR) were 4.15, 5.04, and 6.75 for males, and 4.10, 5.29, and 4.56 for females hypertension, heart disease, and stroke, respectively. Lower income (OR from 1.27—1.94) and lower education (OR from 1.23—1.86) were independently associated with a high prevalence of hypertension, heart disease, and stroke among diabetics. Alcohol consumption (OR from 1.06—1.38), high BMI (OR from 1.17—1.40), physical inactivity (OR from 1.21—2.45), ethnicity, and immigration status were also strongly associated with hypertension, heart disease, and stroke. The adjusted prevalence of hypertension, heart disease, and stroke in the CCHS-2003 health survey in Canada was significantly higher among those with diabetes compared to those without. Other factors such as age, gender, BMI, lifestyle, family incomes, physical activity levels, and socioeconomic status also affected the strength of association between diabetes and resulting comorbidities.

The Health Utilities Index Mark 3 (HUI3) is an important indicator when measuring the health-related quality of life (HRQOL) and assessing the burden of disease, especially for chronic conditions such as diabetes mellitus (DM). The objectives of this study were to evaluate the scores of HRQOL for respondents with DM to examine associations between overall HUI3 scores and eight component attributes, and various sociodemographic and lifestyle attributes, and by doing so, provide information to improve the HRQOL of individuals with diabetes. The study was based on the Canadian National Population Survey (NPHS) longitudinal data, from 1994—1995 to 2002—2003. We evaluated overall HUI3 scores and eight attributes (vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain) between respondents with and without diabetes in relation to demographic characteristics (age, sex, lifestyle, and socioeconomic status using ANCOVA[analysis of covariance]). Awareness of diabetes appeared to affect the HRQOL of older age groups more so than younger age groups (p < 0.01). Diabetes also appeared to have a greater impact on males’ quality of life compared to females', and among individuals with single marital status and low socioeconomic status (p < 0.01). These findings add to what is known about cognitive representations and the self-regulation of diabetes as well as the relationships between cognitive representations of diabetes, HRQOL, and behavioral factors. In particular, results from this study suggest the need to address ways of reducing the burden of diabetes associated with health behaviours, and increasing the quality of life for the individuals with diabetes in Canada.

Quality of life is an important indicator in assessing the burden of disease, especially for chronic conditions. The Health Utilities Index (HUI) is a recently developed system for measuring the overall health status and health-related quality of life (HRQL) of individuals, clinical groups, and general populations. Using the HUI (constructed based on eight attributes: vision, hearing, speech, mobility, dexterity, cognition, emotion, and pain/discomfort) to measure the HRQL for chronic disease patients and to detect possible associations between HUI system and various chronic conditions, this study provides information to improve the management of chronic diseases.This study is of interest to data analysts, policy makers, and public health practitioners involved in descriptive clinical studies, clinical trials, program evaluation, population health planning, and assessments. Based on the Canadian Community Health Survey (CCHS) for 2000–01, the HUI was used to measure the quality of life for individuals living with various chronic conditions (Alzheimer/other dementia, effects of stroke, urinary incontinence, arthritis/rheumatism, bowel disorder, cataracts, back problems, stomach/intestinal ulcers, emphysema/COPD, chronic bronchitis, epilepsy, heart disease, diabetes, migraine headaches, glaucoma, asthma, fibromyalgia, cancers, high blood pressure, multiple sclerosis, thyroid condition, and other remaining chronic diseases). Logistic Regression Model was employed to estimate the associations between the overall HUI scores and various chronic conditions. The HUI scores ranged from 0.00 (corresponding to a state close to death) to 1.00 (corresponding to perfect health); negative scores reflect health states considered worse than death. The mean HUI score by sex and age group indicated the typical quality of life for persons with various chronic conditions. Logistic Regression results showed a strong relationship between low HUI scores (≤ 0.5 and 0.06–1.0) and certain chronic conditions. Age- and sex-adjusted Odds Ratio (OR) and p values showed an effect among individuals diagnosed with each chronic disease on the overall HUI score. Results of this study showed that arthritis/rheumatism, heart disease, high blood pressure, cataracts, and diabetes had a severe impact on HRQL. Urinary incontinence, Alzheimer/other dementia, effects of stroke, cancers, thyroid condition, and back problems have a moderate impact. Food allergy, allergy other than food, asthma, migraine headaches, and other remaining chronic diseases have a relatively mild effect. It is concluded that major chronic diseases with significant health burden were associated with poor HRQL. The HUI scores facilitate the measurement and interpretation of results of health burden and the HRQL for individuals with chronic diseases and can be useful for development of strategies for the prevention and control of chronic diseases.

Abstract Introduction There is currently limited guidance for researchers on Patient and Public Involvement (PPI) for preclinical spinal cord research, leading to uncertainty about design and implementation. This study aimed to develop evidence‐informed principles to support preclinical spinal cord researchers to incorporate PPI into their research. Methods This study used a modified Delphi method with the aim of establishing consensus on a set of principles for PPI in spinal cord research. Thirty‐eight stakeholders including researchers, clinicians and people living with spinal cord injury took part in the expert panel. Participants were asked to rate their agreement with a series of statements relating to PPI in preclinical spinal cord research over two rounds. As part of Round 2, they were also asked to rate statements as essential or desirable. Results Thirty‐eight statements were included in Round 1, after which five statements were amended and two additional statements were added. After Round 2, consensus (> 75% agreement) was reached for a total of 27 principles, with 13 rated as essential and 14 rated as desirable. The principles with highest agreement related to diversity in representation among PPI contributors, clarity of the purpose of PPI and effective communication. Conclusion This research developed a previously unavailable set of evidence‐informed principles to inform PPI in preclinical spinal cord research. These principles provide guidance for researchers seeking to conduct PPI in preclinical spinal cord research and may also inform PPI in other preclinical disciplines. Patient and Public Involvement Statement This study was conducted as part of a project aiming to develop PPI in preclinical spinal cord injury research associated with an ongoing research collaboration funded by the Irish Rugby Football Union Charitable Trust (IRFU CT) and the Science Foundation Ireland Centre for Advanced Materials and BioEngineering Research (SFI AMBER), with research conducted by the Tissue Engineering Research Group (TERG) at the RCSI University of Medicine and Health Sciences. The project aims to develop an advanced biomaterials platform for spinal cord repair and includes a PPI Advisory Panel comprising researchers, clinicians and seriously injured rugby players to oversee the work of the project. PPI is included in this study through the involvement of members of the PPI Advisory Panel in the conceptualisation of this research, review of findings, identification of key points for discussion and preparation of the study manuscript as co‐authors.

BackgroundAmerican Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce. We describe the clinical characteristics and outcome of patients with ACL imported to a tertiary centre in Germany and determine whether species-specific therapy according to the 2014 "LeishMan" group recommendations is associated with cure.MethodsA retrospective chart review was conducted at the Charité Institute of International Health in Berlin. We analysed data on PCR-confirmed ACL cases collected between 2000 and 2023. Systemic therapy included liposomal amphotericin B, miltefosine, pentavalent antimony, ketoconazole or itraconazole. Localized therapy included perilesional pentavalent antimony or paromomycin ointment. Cure was defined as re-epithelialization of ulcers or disappearance of papular-nodular lesions after 3 months of treatment. Logistic regression models were used to quantify the effect of species-specific systemic therapy on the outcome.Results75 cases were analysed. Most patients were male (62%), median age was 35 years, no patient had a history of immunosuppression. The most common reason for travel was tourism (60%), the most common destination was Costa Rica (28%), the median duration of illness was 8 weeks, and most patients presented with ulcers (87%). Lesions were complex in 43%. The most common Leishmania (L.) species was L. braziliensis (28%), followed by L. panamensis (21%). 51/73 (70%) patients were cured after initial therapy and 17/21 (81%) after secondary therapy. Cure after systemic therapy was more frequent when species-specific treatment recommendations were followed (33/45; 73%), compared to when not followed, (6/17; 35%, P = 0.008). This association was independent of age, sex, previous therapy, complex lesions, and Leishmania species (adjusted OR, 5.06; 95% CI, 1.22-24.16).ConclusionsACL is a rare, imported disease in Germany. Complex lesions were common, challenging successful therapy. This study highlights the importance of identifying the parasite species and suggests that a species-specific approach to treatment leads to better outcomes.

Abstract Regulatory authorities must balance ensuring evidence of efficacy and safety of new drugs. Various regulatory pathways, such as the accelerated approval program in the United States (US), allow authorities to quickly approve drugs for severely ill patients by granting market authorization based on surrogate end points and pending confirmatory trials. In this cross‐sectional study, we considered 23 indications of cancer drugs that received accelerated approval by the US Food and Drug Administration (FDA) but were subsequently withdrawn as of April 2023. Our investigation extended to assessing the regulatory status of these accelerated approvals in the European Union (EU) and Japan, examining relevant regulatory documents and identifying factors contributing to the withdrawal in the United States. Comparing regions, we found that for 52% (12/23) and 30% (7/23) of withdrawn accelerated approvals in the United States, sponsors had also sought marketing authorization from the European Medicines Agency (EMA) and Japan's Pharmaceuticals and Medical Devices Agency (PMDA), respectively. As of the April 30, 2023 study cutoff date, 83% (10/12) of drug–indication pairs remained approved by the EMA, while the PMDA retained 100% (7/7). For these indications, the time from FDA withdrawal until the study cutoff date ranged from 0.23 years to 11.45 years for EMA approvals (median: 1.28 years) and 1.10 years to 11.45 years for PMDA approvals (median: 3.22 years). These findings highlight substantial regulatory discrepancies concerning cancer drugs with unconfirmed benefits. Addressing these discrepancies may involve requiring pharmaceutical companies to confirm clinical benefits using more robust end points and fostering international harmonization in regulators' assessment.

Introduction Current traveller health surveillance is ‘top-down’. Mobile-based surveillance could capture infection symptoms in real time. We aimed to evaluate the spectrum of illness in travellers using a mobile app-based system.Methods This study (ClinicalTrials.gov NCT04672577) used an application called Infection Tracking in Travellers (ITIT) that records travel-related illness symptoms with associated geolocation and weather data. The free ITIT app is available in 14 languages. Participants were recruited globally from April 2022 to July 2023. Participants >18 years of age travelled internationally and provided electronic consent. Incentives included the provision of travel health information imported from the WHO website. Symptoms were recorded with daily pop-up questionnaires and symptom severity was assessed using a Likert scale. Two post-travel questionnaires were administered. Logistic mixed models examined factors relating to symptom presence, and a random forest model examined symptom impact.Results 609 participants were recruited until July 2023. Participants had an average age of 37 years (18–79), and an average travel duration of 26 days (2–281). Most participants were travelling for leisure/tourism (401; 66%), followed by ‘visiting friends and relatives’ (99; 16%) and business travel (80; 13%). All continents were visited by at least one traveller. Of 470 registered trips, symptoms were reported on 163 trips (35%). Gastrointestinal symptoms were reported on 87 trips (19%) and respiratory symptoms on 81 trips (17%). The most important factors in predicting the presence of symptoms were duration of travel, travelling in winter and high humidity. Diarrhoea, headache and nausea were symptoms with most impact on daily activities. Post-travel questionnaires showed that 12% of surveyed participants experienced symptoms with several episodes of self-treatment. Two diagnoses were recorded: Lyme disease and amoebic dysentery.Conclusion The digital tool ITIT successfully captures the spectrum of travel-related illness. This detailed epidemiology is crucial for outbreak detection and for the formulation of travel medicine guidelines.Trial registration number NCT04672577.

Abstract Background Antimicrobial resistance has been identified as a major threat to global health. The pig food chain is considered an important source of antimicrobial resistance genes (ARGs). However, there is still a lack of knowledge on the dispersion of ARGs in pig production system, including the external environment. Results In the present study, we longitudinally followed one swine farm located in Italy from the weaning phase to the slaughterhouse to comprehensively assess the diversity of ARGs, their diffusion, and the bacteria associated with them. We obtained shotgun metagenomic sequences from 294 samples, including pig feces, farm environment, soil around the farm, wastewater, and slaughterhouse environment. We identified a total of 530 species-level genome bins (SGBs), which allowed us to assess the dispersion of microorganisms and their associated ARGs in the farm system. We identified 309 SGBs being shared between the animals gut microbiome, the internal and external farm environments. Specifically, these SGBs were characterized by a diverse and complex resistome, with ARGs active against 18 different classes of antibiotic compounds, well matching antibiotic use in the pig food chain in Europe. Conclusions Collectively, our results highlight the urgency to implement more effective countermeasures to limit the dispersion of ARGs in the pig food systems and the relevance of metagenomics-based approaches to monitor the spread of ARGs for the safety of the farm working environment and the surrounding ecosystems.

Human leucocyte antigen class I (HLA-I) molecules play a central role for both NK and T-cell responses that prevent serious human cytomegalovirus (HCMV) disease. To create opportunities for viral spread, several HCMV-encoded immunoevasins employ diverse strategies to target HLA-I. Among these, the glycoprotein US10 is so far insufficiently studied. While it was reported that US10 interferes with HLA-G expression, its ability to manipulate classical HLA-I antigen presentation remains unknown. In this study, we demonstrate that US10 recognizes and binds to all HLA-I (HLA-A, -B, -C, -E, -G) heavy chains. Additionally, impaired recruitment of HLA-I to the peptide loading complex was observed. Notably, the associated effects varied significantly dependending on HLA-I genotype and allotype: (i) HLA-A molecules evaded downregulation by US10, (ii) tapasin-dependent HLA-B molecules showed impaired maturation and cell surface expression, and (iii) β2m-assembled HLA-C, in particular HLA-C*05:01 and -C*12:03, and HLA-G were strongly retained in complex with US10 in the endoplasmic reticulum. These genotype-specific effects on HLA-I were confirmed through unbiased HLA-I ligandome analyses. Furthermore, in HCMV-infected fibroblasts inhibition of overlapping US10 and US11 transcription had little effect on HLA-A, but induced HLA-B antigen presentation. Thus, the US10-mediated impact on HLA-I results in multiple geno- and allotypic effects in a so far unparalleled and multimodal manner.

Abstract During the SARS-CoV-2 pandemic, the German healthcare system faced challenges of efficiently allocating testing resources. To address this, we developed an open-source personalized recommendation system (PRS) called “CovApp”. The PRS utilized a questionnaire to estimate the risk of infection, provided personalized recommendations such as testing, self-isolation, or quarantine, and featured QR code data transmission to electronic health records. The PRS served up to 2.5 million monthly users and received 67,000 backlinks from 1800 domains. We clinically evaluated the PRS at the SARS-CoV-2 testing facility at Charité and observed a 21.7% increase in patient throughput per hour and a 22.5% increase in patients per day. Patients using the PRS were twice as likely to belong to the High Risk group eligible for testing (18.6% vs. 8.9%, p

The increasing digitalization of enterprises and public authorities has resulted in the growing importance of information technology in everyday operations. In this context, an information security management system (ISMS) has become an essential aspect for most organizations. The dependency on technology for almost every single process in an organization has put ISMS at the top of the corporate agenda of public sector organizations. For public organizations in particular, the NIS 2 Directive describes abstract requirements for the development of an ISMS. On the other hand, only a few public administrations operate an ISMS. In this context, this article analyses the requirements of the NIS-2 Directive and complements them with the obstacles and reasons for success in the introduction of ISMS in small public sector organizations (SPSO). At the same time, minimum requirements should be defined that help municipal administration set up an ISMS quickly and easily. This article summarizes the different requirements and generates a foundation for a rough procedural model, for implementing the upcoming requirements of the NIS 2 Directive in local governments. The article also presents the conceptual design of the procedural model.

Abstract Introduction As health reforms move Ireland from a mixed public-private system toward universal healthcare, it is important to understand variations in prescribing practice for patients with differing health cover and socioeconomic status. This study aims to determine how prescribing patterns for patients aged ≥ 65 years in primary care in Ireland differ between patients with public and private health cover. Methods This was an observational study using anonymised data collected as part of a larger study from 44 general practices in Ireland (2011–2018). Data were extracted from electronic records relating to demographics and prescribing for patients aged ≥ 65 years. The cohort was divided between those with public health cover (via the General Medical Services (GMS) scheme) and those without. Standardised rates of prescribing were calculated for pre-specified drug classes. We also analysed the number of medications, polypharmacy, and trends over time between groups, using multilevel linear regression adjusting for age and sex, and hospitalisations. Results Overall, 42,456 individuals were included (56% female). Most were covered by the GMS scheme (62%, n = 26,490). The rate of prescribing in all drug classes was higher for GMS patients compared to non-GMS patients, with the greatest difference in benzodiazepine anxiolytics. The mean number of unique medications prescribed to GMS patients was 10.9 (SD 5.9), and 8.1 (SD 5.8) for non-GMS patients. The number of unique medications prescribed to both GMS and non-GMS cohorts increased over time. The increase was steeper in the GMS group where the mean number of medications prescribed increased by 0.67 medications/year. The rate of increase was 0.13 (95%CI 0.13, 0.14) medications/year lower for non-GMS patients, a statistically significant difference. Conclusion Our study found a significantly larger number of medications were prescribed to patients with public health cover, compared to those without. Increasing medication burden and polypharmacy among older adults may be accelerated for those of lower socioeconomic status. These findings may inform planning for moves towards universal health care, and this would provide an opportunity to evaluate the effect of expanding entitlement on prescribing and medications use.

Abstract The Two Weeks in the World research project has resulted in a dataset of 3087 clinically relevant bacterial genomes with pertaining metadata, collected from 59 diagnostic units in 35 countries around the world during 2020. A relational database is available with metadata and summary data from selected bioinformatic analysis, such as species prediction and identification of acquired resistance genes.

Abstract Introduction Patient and public involvement (PPI) in research is an embedded practice in clinical research, however, its role in preclinical or laboratory‐based research is less well established and presents specific challenges. This study aimed to explore the perspectives of two key stakeholder groups, preclinical researchers and clinicians on PPI in preclinical research, using spinal cord research as a case study. Methods Semi‐structured interviews were conducted online with 11 clinicians and 11 preclinical researchers all working in the area of spinal cord injury (SCI). Interviews were transcribed verbatim and analysed thematically. Findings Nine themes were developed through analysis. Participants' perspectives included that people living with SCI had a right to be involved, that PPI can improve the relevance of preclinical research, and that PPI can positively impact the experiences of researchers. They identified the distance between lab‐based research and the daily experiences of living with SCI to be a barrier and proactive management of accessibility and the motivated and networked SCI community as key facilitators. To develop strong partnerships, participants suggested setting clear expectations, ensuring good communication, and demonstrating respect for the time of PPI contributors involved in the research. Conclusions While traditionally PPI has been more commonly associated with clinical research, participants identified several potential benefits of PPI in preclinical spinal cord research that have applicability to preclinical researchers more broadly. Preclinical spinal researchers should explore how to include PPI in their work. Patient or Public Contribution This study was conducted as part of a broader project aiming to develop an evidence base for preclinical PPI that draws on a 5‐year preclinical research programme focused on the development of advanced biomaterials for spinal cord repair as a case study. A PPI Advisory Panel comprising seriously injured rugby players, clinicians, preclinical researchers, and PPI facilitators collaborated as co‐authors on the conceptualisation, design of the interview protocol, data analysis and writing of this manuscript.

BackgroundThe use of eHealth technology in cardiac rehabilitation (CR) is a promising approach to enhance patient outcomes since adherence to healthy lifestyles and risk factor management during phase III CR maintenance is often poorly supported. However, patients’ needs and expectations have not been extensively analyzed to inform the design of such eHealth solutions. ObjectiveThe goal of this study was to provide a detailed patient perspective on the most important functionalities to include in an eHealth solution to assist them in phase III CR maintenance. MethodsA guided survey as part of a Living Lab approach was conducted in Germany (n=49) and Spain (n=30) involving women (16/79, 20%) and men (63/79, 80%) with coronary artery disease (mean age 57 years, SD 9 years) participating in a structured center-based CR program. The survey covered patients’ perceived importance of different CR components in general, current usage of technology/technical devices, and helpfulness of the potential features of eHealth in CR. Questionnaires were used to identify personality traits (psychological flexibility, optimism/pessimism, positive/negative affect), potentially predisposing patients to acceptance of an app/monitoring devices. ResultsAll the patients in this study owned a smartphone, while 30%-40% used smartwatches and fitness trackers. Patients expressed the need for an eHealth platform that is user-friendly, personalized, and easily accessible, and 71% (56/79) of the patients believed that technology could help them to maintain health goals after CR. Among the offered components, support for regular physical exercise, including updated schedules and progress documentation, was rated the highest. In addition, patients rated the availability of information on diagnosis, current medication, test results, and risk scores as (very) useful. Of note, for each item, except smoking cessation, 35%-50% of the patients indicated a high need for support to achieve their long-term health goals, suggesting the need for individualized care. No major differences were detected between Spanish and German patients (all P>.05) and only younger age (P=.03) but not sex, education level, or personality traits (all P>.05) were associated with the acceptance of eHealth components. ConclusionsThe patient perspectives collected in this study indicate high acceptance of personalized user-friendly eHealth platforms with remote monitoring to improve adherence to healthy lifestyles among patients with coronary artery disease during phase III CR maintenance. The identified patient needs comprise support in physical exercise, including regular updates on personalized training recommendations. Availability of diagnoses, laboratory results, and medications, as part of a mobile electronic health record were also rated as very useful. Trial RegistrationClinicalTrials.gov NCT05461729; https://clinicaltrials.gov/study/NCT05461729

BackgroundPatient and public involvement in research (PPI) has many benefits including increasing relevance and impact. While using PPI in clinical research is now an established practice, the involvement of patients and the public in pre-clinical research, which takes place in a laboratory setting, has been less frequently described and presents specific challenges. This study aimed to explore the perspectives of seriously injured rugby players' who live with a spinal cord injury on PPI in pre-clinical research.MethodsSemi-structured interviews were conducted via telephone with 11 seriously injured rugby players living with spinal cord injury on the island of Ireland. A purposive sampling approach was used to identify participants. Selected individuals were invited to take part via gatekeeper in a charitable organisation that supports seriously injured rugby players. Interviews were transcribed verbatim and analysed thematically.FindingsSix themes were identified during analysis: 'appreciating potential benefits of PPI despite limited knowledge', 'the informed perspectives of people living with spinal cord injury can improve pre-clinical research relevance', 'making pre-clinical research more accessible reduces the potential for misunderstandings to occur', 'barriers to involvement include disinterest, accessibility issues, and fear of losing hope if results are negative', 'personal contact and dialogue helps people feel valued in pre-clinical research, and 'PPI can facilitate effective dissemination of pre-clinical research as desired by people living with spinal cord injury.'ConclusionPeople affected by spinal cord injury in this study desire further involvement in pre-clinical spinal cord injury research through dialogue and contact with researchers. Sharing experiences of spinal cord injury can form the basis of PPI for pre-clinical spinal cord injury research.

Peptide-loaded MHC class I (pMHC-I) multimers have revolutionized our capabilities to monitor disease-associated T cell responses with high sensitivity and specificity. To improve the discovery of T cell receptors (TCR) targeting neoantigens of individual tumor patients with recombinant MHC molecules, we developed a peptide-loadable MHC class I platform termed MediMer. MediMers are based on soluble disulfide-stabilized β2-microglobulin/heavy chain ectodomain single-chain dimers (dsSCD) that can be easily produced in large quantities in eukaryotic cells and tailored to individual patients’ HLA allotypes with only little hands-on time. Upon transient expression in CHO-S cells together with ER-targeted BirA biotin ligase, biotinylated dsSCD are purified from the cell supernatant and are ready to use. We show that CHO-produced dsSCD are free of endogenous peptide ligands. Empty dsSCD from more than 30 different HLA-A,B,C allotypes, that were produced and validated so far, can be loaded with synthetic peptides matching the known binding criteria of the respective allotypes, and stored at low temperature without loss of binding activity. We demonstrate the usability of peptide-loaded dsSCD multimers for the detection of human antigen-specific T cells with comparable sensitivities as multimers generated with peptide-tethered β2m-HLA heavy chain single-chain trimers (SCT) and wild-type peptide-MHC-I complexes prior formed in small-scale refolding reactions. Using allotype-specific, fluorophore-labeled competitor peptides, we present a novel dsSCD-based peptide binding assay capable of interrogating large libraries of in silico predicted neoepitope peptides by flow cytometry in a high-throughput and rapid format. We discovered rare T cell populations with specificity for tumor neoepitopes and epitopes from shared tumor-associated antigens in peripheral blood of a melanoma patient including a so far unreported HLA-C*08:02-restricted NY-ESO-1-specific CD8+ T cell population. Two representative TCR of this T cell population, which could be of potential value for a broader spectrum of patients, were identified by dsSCD-guided single-cell sequencing and were validated by cognate pMHC-I multimer staining and functional responses to autologous peptide-pulsed antigen presenting cells. By deploying the technically accessible dsSCD MHC-I MediMer platform, we hope to significantly improve success rates for the discovery of personalized neoepitope-specific TCR in the future by being able to also cover rare HLA allotypes.

Japan currently enjoys a “VR boom”, a proliferation of commercial virtual reality (VR) programs. As it pertains to disability studies, however, we observe troubling ableist and assimilatory tendencies such as a VR tool for implicit bias training for medical practitioners that promises “simulated experiences” of disabled people, or a VR vocational coaching tool designed to teach disabled people social scripts in professional settings. This article cautions against such stifling and one-dimensional approaches to disability and instead offers more expansive and transformative VR usage based on the creative and pedagogical practices the authors engage with: 1) a VR co-creation approach which revolves around disabled content creators and developers who forge disability-centered community spaces, and 2) a VR intersectional education approach which invites students – regardless of their disability status – to identify their interrelated struggles in an ableist, cisheteronormative, and patriarchal society, realizing their political responsibility for nurturing inclusivity with disabled community members.

This study examined the relationship between share repurchases and corporate sustainability in South Africa during 2011–2019. According to stakeholder theory, companies may feel a sense of obligation to not only distribute returns to shareholders through share repurchases but also to other stakeholders by investing in environmental, social or governance (ESG)-related projects. Our study, the first of its kind in the context of an emerging economy, reported a positive relationship between share repurchases and corporate sustainability in South Africa (proxied using ESG scores)—specifically social scores. The emphasis on the social, rather than the environmental, dimensions of ESG might result from the emerging economy context, where several societal problems are experienced. The results support stakeholder theory, but increased disclosure pertaining to the social dimension of ESG in years when share repurchases are executed might also provide evidence of ‘social washing’ (when companies employ their integrated report disclosures to paint an overly positive picture of their social responsibility initiatives).

Despite the success of chimeric antigen receptor (CAR) T-cells especially for treating hematological malignancies, critical drawbacks, such as “on-target, off-tumor” toxicities, need to be addressed to improve safety in translating to clinical application. This is especially true, when targeting tumor-associated antigens (TAAs) that are not exclusively expressed by solid tumors but also on hea9lthy tissues. To improve the safety profile, we developed switchable adaptor CAR systems including the RevCAR system. RevCAR T-cells are activated by cross-linking of bifunctional adaptor molecules termed target modules (RevTM). In a further development, we established a Dual-RevCAR system for an AND-gated combinatorial targeting by splitting the stimulatory and co-stimulatory signals of the RevCAR T-cells on two individual CARs. Examples of common markers for colorectal cancer (CRC) are the carcinoembryonic antigen (CEA) and the epithelial cell adhesion molecule (EpCAM), while these antigens are also expressed by healthy cells. Here we describe four novel structurally different RevTMs for targeting of CEA and EpCAM. All anti-CEA and anti-EpCAM RevTMs were validated and the simultaneous targeting of CEA+ and EpCAM+ cancer cells redirected specific in vitro and in vivo killing by Dual-RevCAR T-cells. In summary, we describe the development of CEA and EpCAM specific adaptor RevTMs for monospecific and AND-gated targeting of CRC cells via the RevCAR platform as an improved approach to increase tumor specificity and safety of CAR T-cell therapies.

Spatial development plans can be vital tools to guide spatial development in rapidly urbanising towns and cities in the South. Yet, their efficacy in guiding spatial development in Zimbabwe’s volatile environment is increasingly questioned and remains little understood, at least empirically. This paper assesses whether master and local plans positively affect spatial development in cities, towns, and growth centres in Masvingo province. We found that spatial developments undertaken without the guidance of master and local plans are chaotic and result in disorderly settlements. However, the same is evident in urban centres with operative master and local plans. Unplanned settlements have emerged as pressure is mounting on local authorities to provide building land and housing for the ever-increasing urban populations. The blueprint nature and the cost of preparing spatial development plans have discouraged local authorities with intentions to prepare such plans and triggered the need to question their efficacy. Even for local authorities with operative master and local plans: the disregard of these plans by political and economic elites and the urban poor shows that the plans have, in most cases, become inhibitors of development in a rapidly urbanising world. Master and local plans remain essential tools for guiding spatial development in Zimbabwe as long as they become flexible and swiftly respond to the needs of the ever-growing urban population.

Myanmar is one of the world’s most biologically rich countries and has among the largest contiguous intact forest landscapes in southeast Asia. Yet many of its ecosystems are highly threatened and there is an urgent need for greater wildlife conservation action, particularly for its 20 primate species, over half of which are either Endangered or Critically Endangered on the IUCN Red List of Threatened Species. Of these 20 species, three survive in small, isolated populations, while for the remaining 17 there is insufficient population and distribution information to accurately target conservation management and monitoring. To begin to address this challenge, we conducted semi-structured interviews with senior academics and professionals working in primate conservation in Myanmar to assess current knowledge on the conservation status of each of the primate species found there, as well as conservation efforts underway. We also conducted a systematic literature review to generate data on publication metrics for Myanmar primatology. The principal finding is that the populations of nearly all of Myanmar’s 20 primate species are declining, and there are gaps in knowledge on species population dynamics which are hindering conservation action. We present an overview of primatology in Myanmar and address the challenges and recommendations for the future of primate conservation in Myanmar.

Background In Ireland, the means tested General Medical Services (GMS) scheme provides access to a range of healthcare services at no or low cost to approximately one third of the population. Individuals eligible for the GMS scheme are often a focus of research, as a population that account for a large proportion of healthcare services use. The aim of this study is to describe the eligibility rates and representativeness of the GMS scheme population over time, with respect to age group, sex, and geographical area in Ireland. Methods Population data was obtained from the Central Statistics Office (CSO), using 2016 Census figures and projected population figures for 2017-2021. GMS eligibility figures for 2016-2021 were obtained from the HSE Primary Care Reimbursement Service (PCRS). GMS eligibility rates and relative rates of eligibility were calculated for 2016-2021 by age group and sex. Additionally, 2016 eligibility rates were calculated by geographical area. Results The crude eligibility rate decreased from 36.4% in 2016 to 31.2% in 2020, with a slight increase to 31.6% in 2021. In the 75+ years age group, 78.2% of the total population were eligible for the GMS scheme in 2021. The age group with the lowest rate of eligible individuals was the 25–34 age group, with 19.5% eligible in 2021. The eligibility rate was higher among females compared to males throughout the study period. The highest eligibility rate was seen in Donegal, with a crude rate of 52.8%. Dublin had the lowest rate, with a crude rate of 29.3%. Conclusions GMS eligibility varies greatly depending on age, sex, and geographical area, and decreased between 2016 and 2021. This study uses the most up-to-date data available to provide age group, sex and area-based figures for GMS eligibility which may inform planning and conduct of research focusing on GMS-eligible individuals.

Abstract Background Polypharmacy and associated potentially inappropriate prescribing (PIP) place a considerable burden on patients and represent a challenge for general practitioners (GPs). Integration of pharmacists within general practice (herein ‘pharmacist integration’) may improve medications management and patient outcomes. This systematic review assessed the effectiveness and costs of pharmacist integration. Methods A systematic search of ten databases from inception to January 2021 was conducted. Studies that evaluated the effectiveness or cost of pharmacist integration were included. Eligible interventions were those that targeted medications optimization compared to usual GP care without pharmacist integration (herein ‘usual care’). Primary outcomes were PIP (as measured by PIP screening tools) and number of prescribed medications. Secondary outcomes included health-related quality of life, health service utilization, clinical outcomes, and costs. Randomised controlled trials (RCTs), non-RCTs, interrupted-time-series, controlled before-after trials and health-economic studies were included. Screening and risk of bias using Cochrane EPOC criteria were conducted by two reviewers independently. A narrative synthesis and meta-analysis of outcomes where possible, were conducted; the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Results In total, 23 studies (28 full text articles) met the inclusion criteria. In ten of 11 studies, pharmacist integration probably reduced PIP in comparison to usual care (moderate certainty evidence). A meta-analysis of number of medications in seven studies reported a mean difference of -0.80 [-1.17, -0.43], which indicated pharmacist integration probably reduced number of medicines (moderate certainty evidence). It was uncertain whether pharmacist integration improved health-related quality of life because the certainty of evidence was very low. Twelve health-economic studies were included; three investigated cost effectiveness. The outcome measured differed across studies limiting comparisons and making it difficult to make conclusions on cost effectiveness. Conclusions Pharmacist integration probably reduced PIP and number of medications however, there was no clear effect on other patient outcomes; and while interventions in a small number of studies appeared to be cost-effective, further robust, well-designed cluster RCTs with economic evaluations are required to determine cost-effectiveness of pharmacist integration. Trial registration CRD42019139679.

La enseñanza de la Química es de las más costosas en el mundo por la cantidad de equipos,útiles, reactivos químicos e insumos; de ahí la importancia de aprovechar al máximo las actividades experimentales en el proceso de enseñanza-aprendizaje. En correspondencia a ello,el presente artículo tiene como objetivo diseñar actividades experimentales para el desarrollo del proceso de enseñanza-aprendizaje de la Química de 9nogrado en la ESBU “Ana Betancourt de Mora”. Se aplicaron métodos del nivel teórico, empírico y matemático-estadístico en el estadio inicial y final de la investigación, al igual la aplicación de la técnica prueba pedagógica de entrada y salida. Se obtiene un diseño de actividades experimentales con una estructura metodológica ajustada, que comprende sustituciones de útiles de laboratorio, planificación y preparación del profesor, además de tareas que contribuyen a la formación general integral del educando, logrando el desarrollo del pensamiento lógico y la independencia cognoscitiva.

Abstract Background Patient and Public Involvement (PPI) in research aims to improve the quality, relevance and appropriateness of research. PPI has an established role in clinical research where there is evidence of benefit, and where policymakers and funders place continued emphasis on its inclusion. However, for preclinical research, PPI has not yet achieved the same level of integration. As more researchers, including our team, aim to include PPI in preclinical research, the development of an evidence‐based approach is important. Therefore, this scoping review aimed to identify and map studies where PPI has been used in preclinical research and develop principles that can be applied in other projects. Methods A scoping review was conducted to search the literature in Medline (PubMed), EMBASE, CINAHL, PsycInfo and Web of Science Core Collection to identify applied examples of preclinical PPI. Two independent reviewers conducted study selection and data extraction separately. Data were extracted relating to PPI in terms of (i) rationale and aims, (ii) approach used, (iii) benefits and challenges, (iv) impact and evaluation and (v) learning opportunities for preclinical PPI. Findings were reviewed collaboratively by PPI contributors and the research team to identify principles that could be applied to other projects. Results Nine studies were included in the final review with the majority of included studies reporting PPI to improve the relevance of their research, using approaches such as PPI advisory panels and workshops. Researchers report several benefits and challenges, although evidence of formal evaluation is limited. Conclusion Although currently there are few examples of preclinical research studies reporting empirical PPI activity, their findings may support those aiming to use PPI in preclinical research. Through collaborative analysis of the scoping review findings, several principles were developed that may be useful for other preclinical researchers. Patient or Public Contribution This study was conducted as part of a broader project aiming to develop an evidence base for preclinical PPI that draws on a 5‐year preclinical research programme focused on the development of advanced biomaterials for spinal cord repair as a case study. A PPI Advisory Panel comprising seriously injured rugby players, clinicians, preclinical researchers and PPI facilitators collaborated as co‐authors on the conceptualization, execution and writing of this review, including refining the findings into the set of principles reported here.

Abstract Introduction The SPPiRE cluster randomized controlled trial found that a general practitioner (GP)‐delivered medication review that incorporated screening for potentially inappropriate prescriptions (PIP), a brown bag review and a patient priority assessment, resulted in a significant but small reduction in the number of medicines and no significant reduction in PIP. This process evaluation aims to explore the experiences of GPs and patients and the potential for system‐wide implementation. Methods The trial included 51 general practices and 404 participants with multimorbidity aged ≥65 years, prescribed ≥15 medicines. The process evaluation used mixed methods and ran parallel to the trial. Quantitative data was collected from the SPPiRE intervention website and analysed descriptively. Qualitative data on medication changes were collected from intervention GPs (18/26) and a purposive sample of intervention patients (27/208) via semi‐structured telephone interviews. All interviews were transcribed verbatim and analysed using a thematic analysis. Qualitative and quantitative data were integrated using a triangulation protocol. Results The analysis generated two themes, intervention implementation and mechanisms of action, and both were underpinned by the theme of context. Intervention delivery varied among practices and 45 patients (28%) had no review, primarily due to insufficient GP time. 80% of reviewed patients had ≥1 PIP identified, 59% had ≥1 problem identified during the brown bag review and 79% had ≥1 priority recorded. The brown bag review resulted in the most deprescription of medications. GPs and patients responded positively to the intervention but most GPs did not engage with the patient priority‐setting process. GPs identified a lack of integration into practice software and resources as barriers to future implementation. Conclusion The SPPiRE intervention had a small effect in reducing the number of medicines and this was primarily mediated through the brown bag review. The context of resource shortages and deep‐seated views around medical decision‐making influenced intervention implementation. Patient or Public Contribution Qualitative data on the implementation of the medication review and their wider views on their medicines was collected from older people with multimorbidity through semi‐structured telephone interviews. Clinical Trial Registration The SPPiRE trial was registered prospectively on the ISRCTN registry (ISRCTN12752680).

Maoism is a global political and ideological current, emerged in the course of the Chinese revolution during the first half of the 20th century, but turned into a revolutionary project with a global reach. In this sense, this article proposes a synthesis look at the studies of global history of Maoism, pointing out its contributions, discussions, limitations, to understand the richness of the history of the communist lefts in the world, not as a past overcome, but as a present past, active and related to contemporary emancipatory struggles.

Abstract Temperature variability may have direct and indirect impacts on the environments of the Accra and Kumasi Metropolises in Ghana. This study analysed temperature and trends in temperature in both cities using in-situ measurements from one meteorological station in both cities from 1986 to 2015. The temperature indices were computed using the RClimdex package from the Expert Team on Climate Change Detection Monitoring Indices (ETCCDMI). The temperature time series was pre-whitened before the Mann–Kendall trend and Sen’s slope estimator analysis were applied. Initial analysis revealed minimal variation in temperature in both cities. The results from the analysed temperature indices revealed an increase in warm days and a general rise in the minimum temperature compared to maximum temperatures. Mann Kendall and Sen’s slope revealed significant trends in the annual and seasonal (dry and wet seasons) in minimum temperature in both cities. These might lead to an increased rate of heat-stressed diseases and an overall rise in urban warming in both cities. The analysis of temperature, indices and trends provided comprehensive insights into the temperature of Accra and Kumasi. The results highlight the essence of evaluating temperature indices and trends in light of Climate Change concerns. It is recommended that urban green and blue spaces should be incorporated into land use plans as these policy directions can aid regulate the temperature in both cities.

Abstract Purpose To inform recommendations by the Canadian Task Force on Preventive Health Care on potentially inappropriate prescribing and over-the-counter (OTC) medication use among adults aged 65 years and older in primary care settings. This protocol outlines the planned scope and methods for a systematic review of the benefits and harms and acceptability of interventions to reduce potentially inappropriate prescriptions and OTC medication use. Methods De novo systematic reviews will be conducted to synthesize the available evidence on (a) the benefits and harms of interventions to reduce potentially inappropriate prescriptions and OTC medications compared to no intervention, usual care, or non- or minimally active intervention among adults aged 65 years and older and (b) the acceptability of these interventions or attributes among patients. Outcomes of interest for the benefits and harms review are all-cause mortality, hospitalization, non-serious adverse drug reactions, quality of life, emergency department visits, injurious falls, medical visits, and the number of medications (and number of pills). Outcomes for the acceptability review are the preference for and relative importance of different interventions or their attributes. For the benefits and harms review, we will search MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials. For the acceptability review, we will search MEDLINE, Embase, PsycInfo, Cochrane Central Register of Controlled Trials, and the NHS Economic Evaluation Database for experimental and observational studies with a comparator. Websites of relevant organizations, other grey literature sources, and reference lists of included studies and reviews will be searched. Title and abstract screening will be completed by two independent reviewers using the liberal accelerated approach. Full-text review, data extraction, risk of bias assessments, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers, with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE approach will be used to assess the certainty of the evidence for outcomes. Discussion The results of this systematic review will be used by the Canadian Task Force on Preventive Health Care to inform their recommendation on potentially inappropriate prescribing and OTC medication use among adults aged 65 years and older. Systematic review registration PROSPERO (KQ1: CRD42022302313; KQ2: CRD42022302324); Open Science Framework ( https://osf.io/urj4b/ ).

Background: Metabolic conditions, including intermediate hyperglycemia (IH), affect migrants to a greater extent than the populations of origin. Evidence suggests that IH increases the risk of vascular complications, but it is unclear whether the differences in IH between the non-migrant and migrant populations translate to differences in vascular complications between the two populations. We compared the prevalence of macrovascular and renal microvascular complications among West Africans with IH living in West Africa and their migrant compatriots in Europe. Methods: Data from the multicenter Research on Obesity and Diabetes among African Migrants(RODAM) study were analyzed. Ghanaians with IH(524 non-migrant and 1439 migrants) were included. Logistic regression analyses were used to determine the associations between migrant status and macrovascular [coronary artery disease(CAD) and peripheral artery disease(PAD)] and renal microvascular[nephropathy] complications with adjustment for age, sex, socioeconomic status, smoking, systolic blood pressure, BMI, total cholesterol, HbA1c, C-reactive protein, and serum uric acid. Findings: The prevalence of microvascular/macrovascular complications was higher in non-migrants than in migrants(nephropathy 15.3vs.9.7%; PAD 3.1%vs.1.3%; and CAD 15.8% vs. 5.0%). The differences persisted in the fully adjusted model: nephropathy [odds ratio, 2.12; 95% CI(1.46–3.08); PAD, 4.44(1.87–10.51); CAD 2.35(1.64–3.37)]. Non-migrant females had higher odds of nephropathy[2.14(1.34–3.43)], PAD[7.47(2.38–23.40)] and CAD [2.10(1.34–3.27)] compared to migrant females. Non-migrant males had higher odds of nephropathy[2.54(1.30–4.97)] and CAD[2.85(1.48–5.50)], but not PAD[1.81(0.32–10.29)],than their migrant peers. Interpretation: Macrovascular and renal microvascular complications were more prevalent in non-migrants than in migrant West Africans with IH. Further studies are needed to identify factors that increase the risk to aid preventive/treatment strategies.

Abstract Background Chronic diseases are the leading cause of death worldwide. Many of these diseases have modifiable risk factors, including physical activity and sleep, and may be preventable. This study investigated independent associations of physical activity and sleep with eight common chronic illnesses. Methods Data were from waves 1, 3 and 5 of The Irish Longitudinal Study on Ageing (n = 5,680). Inverse probability weighted general estimating equations were used to examine longitudinal lifetime prevalence and cumulative incidence of self-reported conditions. Results Sleep problems were significantly associated with increased odds of incident and prevalent arthritis and angina. Additionally sleep problems were associated with higher odds of lifetime prevalence of hypertension and diabetes. Physical activity was negatively associated incident osteoporosis and respiratory diseases and negatively associated with lifetime prevalence of hypertension, high cholesterol and diabetes. Conclusions Worse sleep quality and lower physical activity were associated with higher odds of chronic diseases. Interventions to improve sleep and physical activity may improve health outcomes.

Introduction: The role of community pharmacists has evolved in recent years with expansion in pharmacy services offered. The extent to which patients utilise such services in community pharmacies in Ireland is unclear. Objective: To assess pharmacy services use among adults aged ≥56 years in Ireland, and determine the demographic and clinical factors associated with pharmacy services use. Methods: This cross-sectional study included community-dwelling participants in wave 4 of The Irish Longitudinal Study on Ageing (TILDA), aged ≥56 years who were self-respondents. TILDA is a nationally representative cohort study, with wave 4 data collected during 2016. TILDA collects participant demographics and health data, in addition to information on the use of several services when visiting the pharmacy in the last 12 months. Characteristics and pharmacy services use were summarised. Multivariate logistic regression was used to examine the association of demographic and health factors with reporting (i) any pharmacy service use and (ii) requesting medicines advice. Results: Among 5782 participants (55.5% female, mean age 68 years), 96.6% (5587) reported visiting a pharmacy in the previous 12 months, and almost one fifth of these (1094) utilised at least one non-dispensing pharmacy service. The most common non-dispensing services reported were requesting advice about medications (786, 13.6%), blood pressure monitoring (184, 3.2%), and vaccination (166, 2.9%). Controlling for other factors, female sex (odds ratio (OR) 1.32, 95% CI 1.14–1.52), third-level education (OR 1.85, 95% CI 1.51–2.27), higher rates of GP visits, private health insurance (OR 1.29, 95% CI 1.07–1.56), higher number of medications, loneliness, and respiratory condition diagnosis (OR 1.42, 95% CI 1.14–1.74) were associated with higher likelihood of utilising pharmacy services. The relationship between these factors and requesting medicines advice was similar. Conclusion: A high proportion of middle-aged and older adults visit community pharmacy and a fifth utilise specified pharmacy services. Despite advances in the services offered in pharmacies, medicines advice remains at the core of pharmacists' practice.

Objectives To describe the characteristics of clinical study report (CSR) documents published by the European Medicines Agency (EMA), and for included pivotal trials, to quantify the timeliness of access to trial results from CSRs compared with conventional published sources.Design Cross-sectional analysis of CSR documents published by the EMA from 2016 to 2018.Methods CSR files and medication summary information were downloaded from the EMA. Individual trials in each submission were identified using document filenames. Number and length of documents and trials were determined. For pivotal trials, trial phase, dates of EMA document publication and matched journal and registry publications were obtained.Results The EMA published documents on 142 medications that were submitted for regulatory drug approval. Submissions were for initial marketing authorisations in 64.1%. There was a median of 15 (IQR 5–46) documents, 5 (IQR 2–14) trials and 9629 (IQR 2711–26,673) pages per submission, and a median of 1 (IQR 1–4) document and 336 (IQR 21–1192) pages per trial. Of all identified pivotal trials, 60.9% were phase 3 and 18.5% were phase 1. Of 119 unique submissions to the EMA, 46.2% were supported by a single pivotal trial, with 13.4% based on a single pivotal phase 1 trial. No trial registry results were identified for 26.1% trials, no journal publications for 16.7% and 13.5% of trials had neither. EMA publication was the earliest information source for 5.8% of pivotal trials, available a median 523 days (IQR 363–882 days) before the earliest publication.Conclusions The EMA Clinical Data website contains lengthy clinical trial documents. Almost half of submissions to the EMA were based on single pivotal trials, many of which were phase 1 trials. CSRs were the only source and a timelier source of information for many trials. Access to unpublished trial information should be open and timely to support decision-making for patients.

Abstract Objective To address the gap in the literature and using a novel open-source intelligence web-scraping approach, this paper investigates the longitudinal relationships between availability, value, and disposability, and stealing counts of specific makes and models of gaming consoles. Methods Using data from Western Australia (2012–2019) and focusing on specific makes/models of gaming consoles, the relationships between product-specific stealing counts, availability, value, and disposability were examined using time series and cross-sectional analyses. Results Support was found for a positive relationship between the changing disposability of specific makes/models of gaming consoles over their lifecycle with corresponding stealing counts, above and beyond changes in availability and value. However, when these attributes were analysed statically, both disposability and value were important. Conclusions The results highlight the importance of measuring correlates of ‘hot products’ longitudinally to better understand offenders’ target selection preferences over time—with important implications for theft risk assessment and crime prevention policy and practice. These findings also provide support for the use of similar open-source intelligence web-scraping strategies as a suitable technique for capturing time-specific proxies for product-specific value and disposability.

Background: Reliable data on health care costs in Ireland are essential to support planning and evaluation of services. New unit costs and high-quality utilisation data offer the opportunity to estimate individual-level costs for research and policy. Methods: Our main dataset was The Irish Longitudinal Study on Ageing (TILDA). We used participant interviews with those aged 55+ years in Wave 5 (2018) and all available end-of-life interviews (EOLI) to February 2020. We weighted observations by age, sex and last year of life at the population level. We estimated total formal health care costs by combining reported usage in TILDA with unit costs (non-acute care) and public payer reimbursement data (acute hospital admissions, medications). All costs were adjusted for inflation to 2022, the year of analysis. We examined distribution of estimates across the population, and the composition of costs across categories of care, using descriptive statistics. We identified factors associated with total costs using generalised linear models. Results: There were 5,105 Wave 5 observations, equivalent at the population level to 1,207,660 people aged 55+ years and not in the last year of life, and 763 EOLI observations, equivalent to 28,466 people aged 55+ years in the last year of life. Mean formal health care costs in the weighted sample were EUR 8,053; EUR 6,624 not in the last year of life and EUR 68,654 in the last year of life. Overall, 90% of health care costs were accounted for by 20% of users. Multiple functional limitations and proximity to death were the largest predictors of costs. Other factors that were associated with outcome included educational attainment, entitlements to subsidised care and serious chronic diseases. Conclusions: Understanding the patterns of costs, and the factors associated with very high costs for some individuals, can inform efforts to improve patient experiences and optimise resource allocation.

IntroductionFor Streptococcus pneumoniae, β-lactam susceptibility can be predicted from the amino acid sequence of the penicillin-binding proteins PBP1a, PBP2b, and PBP2x. The combination of PBP-subtypes provides a PBP-profile, which correlates to a phenotypic minimal inhibitory concentration (MIC). The non-S. pneumoniae Mitis-group streptococci (MGS) have similar PBPs and exchange pbp-alleles with S. pneumoniae. We studied whether a simple BLAST analysis could be used to predict phenotypic susceptibility in Danish S. pneumoniae isolates and in internationally collected MGS.MethodIsolates with available WGS and phenotypic susceptibility data were included. For each isolate, the best matching PBP-profile was identified by BLAST analysis. The corresponding MICs for penicillin and ceftriaxone was retrieved. Category agreement (CA), minor-, major-, and very major discrepancy was calculated. Genotypic-phenotypic accuracy was examined with Deming regression.ResultsAmong 88 S. pneumoniae isolates, 55 isolates had a recognized PBP-profile, and CA was 100% for penicillin and 98.2% for ceftriaxone. In 33 S. pneumoniae isolates with a new PBP-profile, CA was 90.9% (penicillin) and 93.8% (ceftriaxone) using the nearest recognized PBP-profile. Applying the S. pneumoniae database to non-S. pneumoniae MGS revealed that none had a recognized PBP-profile. For Streptococcus pseudopneumoniae, CA was 100% for penicillin and ceftriaxone in 19 susceptible isolates. In 33 Streptococcus mitis isolates, CA was 75.8% (penicillin) and 86.2% (ceftriaxone) and in 25 Streptococcus oralis isolates CA was 8% (penicillin) and 100% (ceftriaxone).ConclusionUsing a simple BLAST analysis, genotypic susceptibility prediction was accurate in Danish S. pneumoniae isolates, particularly in isolates with recognized PBP-profiles. Susceptibility was poorly predicted in other MGS using the current database.

Este artículo recoge los principales resultados de un estudio que indagó los efectos formativos y socioemocionales provocados por la pandemia de la Covid-19 y la implementación de estrategias de educación remota en los estudiantes del programa de Licenciatura en Ciencias Sociales de la Universidad Distrital Francisco José de Caldas, en Bogotá (Colombia). A partir de una estrategia metodológica de encuesta aplicada en línea a una muestra de 297 estudiantes, se identificaron problemas menores de accesibilidad y conectividad. No obstante, se encontraron deficiencias en materia de capital digital e impactos importantes en el plano motivacional y emocional que afectaron la disposición estudiantil frente a los procesos formativos, y provocaron desconexión académica y agotamiento físico y psicológico. El análisis evidencia que, pasada la crisis sanitaria, los efectos de la misma en la educación superior van a tener consecuencias en materia de desempeño académico, bienestar estudiantil y en la construcción y reconstrucción de proyectos personales y profesionales vinculados con la experiencia universitaria.

ObjectiveTo analyze the impact of the COVID-19 pandemic on medical care and vaccination acceptance of vasculitis patients in Germany.MethodsA web-based national survey was developed by rheumatology centers and vasculitis patient advocacy groups. The survey was distributed nationwide by mail and flyers and could be accessed via a QR-code or weblink from December 2021 to April 2022. Descriptive statistics [mean, median, standard derivation (SD), 25%, 75% quantile] were calculated. 95% confidence intervals were presented for responses that were directly related to the impact of COVID-19 on parameters associated with vasculitis patient care.ResultsThe online survey was completed by 117 patients with small and large vessel vasculitis [granulomatosis with polyangiitis (n = 69), eosinophilic granulomatosis with polyangiitis (n = 16), microscopic polyangiitis (n = 12), giant cell arteritis (n = 17) and Takayasu's arteritis (n = 3)]. Prescheduled rheumatological appointments had been canceled due to the COVID-19 pandemic in 12.6% of the respondents [95% confidence interval (CI), 7.3–20.0%); in 9% (95% CI, 4.5–15.6%)] appointments had been replaced by digital services. Therapeutic regimens were changed (shifted, reduced, or discontinued) due to the pandemic in 15.5% (95% CI 9.5–22.2%). Vaccination coverages were generally high compared to patients with other rheumatic diseases and the general population. Highest vaccination coverage was observed against COVID-19 (98.1% 95% CI 93.9–99.6%).ConclusionVasculitis patients experienced changes in medical care during COVID-19 pandemic such as cancelation of prescheduled rheumatology appointments and modifications in therapeutic regimens. The overall acceptance rate for vaccination was comparatively high, particularly for vaccination against COVID-19.

Objective Reporting guidelines can improve dissemination and application of findings and help avoid research waste. Recent studies reveal opportunities to improve primary care (PC) reporting. Despite increasing numbers of guidelines, none exists for PC research. This study aims to prioritise candidate reporting items to inform a reporting guideline for PC research.Design Delphi study conducted by the Consensus Reporting Items for Studies in Primary Care (CRISP) Working Group.Setting International online survey.Participants Interdisciplinary PC researchers and research users.Main outcome measures We drew potential reporting items from literature review and a series of international, interdisciplinary surveys. Using an anonymous, online survey, we asked participants to vote on and whether each candidate item should be included, required or recommended in a PC research reporting guideline. Items advanced to the next Delphi round if they received>50% votes to include. Analysis used descriptive statistics plus synthesis of free-text responses.Results 98/116 respondents completed round 1 (84% response rate) and 89/98 completed round 2 (91%). Respondents included a variety of healthcare professions, research roles, levels of experience and all five world regions. Round 1 presented 29 potential items, and 25 moved into round 2 after rewording and combining items and adding 2 new items. A majority of round 2 respondents voted to include 23 items (90%–100% for 11 items, 80%–89% for 3 items, 70%–79% for 3 items, 60%–69% for 3 items and 50%–59% for 3 items).Conclusion Our Delphi study identified items to guide the reporting of PC research that has broad endorsement from the community of producers and users of PC research. We will now use these results to inform the final development of the CRISP guidance for reporting PC research.

Introduction: A number of significant changes designed to reduce the spread of COVID-19 were introduced in primary care during the COVID-19 pandemic. In Ireland, these included fundamental legislative and practice changes such as permitting electronic transfer of prescriptions, extending duration of prescription validity, and encouraging virtual consultations. Although such interventions served an important role in preventing the spread of infection, their impact on practice and patient care is not yet clear. The aim of this study was to investigate patient and healthcare professional (pharmacist and general practitioner) experiences to understand the impact of COVID-19 on primary care and medication safety during the first two years of the COVID-19 pandemic in Ireland. Methods: A qualitative study using semi-structured interviews was undertaken between October 2021 and January 2022. Participants included twelve patients, ten community pharmacists, and one general practitioner. Interviews were transcribed verbatim and analysed using thematic analysis. Only patient and pharmacist interviews were included. Findings: Themes from the interviews included: 1) Access to care, 2) Technological changes, 3) Experiences of care, and 4) Patient safety. Particular challenges identified included the difficulty faced by patients when accessing care, impacts on experiences of patient care, and extensive changes to pharmacy practice during the pandemic. Conclusions: This study found that COVID-19 countermeasures considerably impacted patient and pharmacist experiences of primary care in terms of care and medication safety. While many changes were welcomed, others such as virtual consultations were received more cautiously likely due to the rapid and unplanned nature of their introduction. Further research is needed to identify how to optimise these changes to improve pharmacist and patient experience, and to understand the impact on patient safety.

Despite the availability of an effective prophylactic vaccine, 820,000 people die annually of hepatitis B virus (HBV)-related liver disease according to WHO. Since current antiviral therapies do not provide a curative treatment for the 296 million HBV carriers around the globe, novel strategies to cure HBV are urgently needed. A promising approach is the redirection of T cells towards HBV-infected hepatocytes employing chimeric antigen receptors or T-cell engager antibodies. We recently described the effective redirection of T cells employing a second-generation chimeric antigen receptor directed against the envelope protein of hepatitis B virus on the surface of infected cells (S-CAR) as well as bispecific antibodies that engage CD3 or CD28 on T cells employing the identical HBV envelope protein (HBVenv) binder. In this study, we added a trispecific antibody comprising all three moieties to the tool-box. Cytotoxic and non-cytolytic antiviral activities of these bi- and trispecific T-cell engager antibodies were assessed in co-cultures of human PBMC with HBV-positive hepatoma cells, and compared to that of S-CAR-grafted T cells. Activation of T cells via the S-CAR or by either a combination of the CD3- and CD28-targeting bispecific antibodies or the trispecific antibody allowed for specific elimination of HBV-positive target cells. While S-CAR-grafted effector T cells displayed faster killing kinetics, combinatory treatment with the bispecific antibodies or single treatment with the trispecific antibody was associated with a more pronounced cytokine release. Clearance of viral antigens and elimination of the HBV persistence form, the covalently closed circular (ccc) DNA, through cytolytic as well as cytokine-mediated activity was observed in all three settings with the combination of bispecific antibodies showing the strongest non-cytolytic, cytokine-mediated antiviral effect. Taken together, we demonstrate that bi- and trispecific T-cell engager antibodies can serve as a potent, off-the-shelf alternative to S-CAR-grafted T cells to cure HBV.

Background: In Ireland, the means tested General Medical Services (GMS) scheme provides access to a range of healthcare services at no or low cost to approximately one third of the population. Individuals eligible for the GMS scheme are often a focus of research, as a population that account for a large proportion of healthcare services use. The aim of this study is to describe the eligibility rates and representativeness of the GMS scheme population over time, with respect to age group, sex, and geographical area in Ireland. Methods: Population data was obtained from the Central Statistics Office (CSO), using 2016 Census figures and projected population figures for 2017-2021. GMS eligibility figures for 2016-2021 were obtained from the HSE Primary Care Reimbursement Service (PCRS). GMS eligibility rates and relative rates of eligibility were calculated for 2016-2021 by age group and sex. Additionally, 2016 eligibility rates were calculated by geographical area. Results: The crude eligibility rate decreased from 36.4% in 2016 to 31.2% in 2020, with a slight increase to 31.6% in 2021. In the 75+ years age group, 78.2% of the total population were eligible for the GMS scheme in 2021. The age group with the lowest rate of eligible individuals was the 25-34 age group, with 19.5% eligible in 2021. The eligibility rate was higher among females compared to males throughout the study period. The highest eligibility rate was seen in Donegal, with a crude rate of 52.8%. Dublin had the lowest rate, with a crude rate of 29.3%. Conclusions: GMS eligibility varies greatly depending on age, sex, and geographical area, and decreased between 2016 and 2021. This study uses the most up-to-date data available to provide age group, sex and area-based figures for GMS eligibility which may inform planning and conduct of research focusing on GMS-eligible individuals.