Formal Guidelines Research Articles

Assessing Hybridization-Dependent Off-Target Risk for Therapeutic Oligonucleotides: Updated Industry Recommendations.

Hybridization-dependent off-target (OffT) effects, occurring when oligonucleotides bind via Watson-Crick-Franklin hybridization to unintended RNA transcripts, remain a critical safety concern for oligonucleotide therapeutics (ONTs). Despite the importance of OffT assessment of clinical trial ONT candidates, formal guidelines are lacking, with only brief mentions in Japanese regulatory documents (2020) and US Food and Drug Administration (FDA) recommendations for hepatitis B virus treatments (2022). This article presents updated industry recommendations for assessing OffTs of ONTs, building upon the 2012 Oligonucleotide Safety Working Group (OSWG) recommendations and accounting for recent technological advancements. A new OSWG subcommittee, comprising industry experts in RNase H-dependent and steric blocking antisense oligonucleotides and small interfering RNAs, has developed a comprehensive framework for OffT assessment. The proposed workflow encompasses five key steps: (1) OffT identification through in silico complementarity prediction and transcriptomics analysis, (2) focus on cell types with relevant ONT activity, (3) in vitro verification and margin assessment, (4) risk assessment based on the OffT biological role, and (5) management of unavoidable OffTs. The authors provide detailed considerations for various ONT classes, emphasizing the importance of ONT-specific factors such as chemistry, delivery systems, and tissue distribution in OffT evaluation. The article also explores the potential of machine learning models to enhance OffT prediction and discusses strategies for experimental verification and risk assessment. These updated recommendations aim to improve the safety profile of ONTs entering clinical trials and to manage unavoidable OffTs. The authors hope that these recommendations will serve as a valuable resource for ONT development and for the forthcoming finalization of the FDA draft guidance and the International Council for Harmonization S13 guidance on Nonclinical Safety Assessment of Oligonucleotide-Based Therapeutics.

Urban Parks in Permanent Preservation Areas as a Tool for Conservation and Environmental Education: a Bibliometric Study

Objective: This study investigated the scientific production on Urban Parks in Permanent Preservation Areas (APPs), focusing on their multifunctionality in environmental conservation and ecological education. Theoretical Framework: The study is based on the National Environmental Education Policy (Law nº 9.795/1999) and research highlighting Urban Parks as strategic spaces for environmental balance and collective awareness. Method: A bibliometric analysis was conducted using the Scopus database, covering 562 documents published between 1979 and 2023. The VOSviewer software was used to identify co-authorship networks, keywords, and thematic patterns. Results and Discussion: Urban Parks in APPs have great potential for sustainability and environmental education but are underutilized as pedagogical tools. Expanding the integration between conservation and education through public policies, experimental projects, and participatory management strategies is recommended. This study contributes to the formulation of guidelines to maximize the impact of these spaces on urban quality of life and environmental awareness. Originality/Value: This study provides a comprehensive overview of the scientific landscape on Urban Parks in APPs, identifying key trends, gaps, and opportunities for future research. It highlights the underexplored potential of these spaces as tools for environmental education and suggests strategic actions to enhance their multifunctionality. The findings offer valuable insights for researchers, policymakers, and practitioners in urban planning and environmental management.

Governance in Universities: the Mechanism of Leadership and the Experience of the Federal University of Sergipe

Objective: To analyze the need to consolidate governance systems in Federal Universities, highlighting leadership as an essential pillar and using the Federal University of Sergipe (UFS) as a reference. Theoretical Framework: The research is grounded in the concepts of public governance as described in Decree No. 9,203/2017 and the guidelines of the Federal Court of Accounts (TCU). Leadership is emphasized as a central element. Within the context of federal universities, the study examines the impact of governance on the interaction with institutional autonomy, while addressing challenges and innovations in the field, such as the experience of the Federal University of Sergipe (UFS). Method: A document analysis of key governance and management documents from Brazilian federal universities was conducted, with a focus on the Federal University of Sergipe. The UFS document analysis covered a time frame of eight years. The results were organized into categories. Results and Discussion: The research identified significant advances in the governance of the Federal University of Sergipe (UFS). The findings show improvements in performance indicators, aligned with the guidelines of Decree No. 9,203/2017 and the TCU. Nevertheless, challenges remain. The proposal of a research agenda underscores the need to deepen the discussion and explore new solutions. Research Implications: The practical and theoretical implications of this research include consolidating governance systems as a reference for strengthening public university management. Originality/Value: The research contributes to the formulation of guidelines and replicable models for other federal universities, fostering greater institutional cohesion and alignment with public policies.

Expert consensus on the diagnosis and treatment of neurobrucellosis (2025 edition)

Neurobrucellosis is a neurological disorder caused by Brucella infection. It typically occurs as part of the multisystem involvement of brucellosis, or may also present as brucellosis. The existing clinical practice guidelines and expert consensus on human brucellosis are outdated and provide limited guidance specific to the diagnosis and management of neurobrucellosis, failing to meet the evolving needs of healthcare providers and patients. To comprehensively improve the diagnostic and therapeutic capabilities for neurobrucellosis in China, as well as to standardize clinical practice of diagnosis and treatment for neurobrucellosis, the Tuberculous Meningitis Subcommittee of the Tuberculosis Branch of the Chinese Medical Association established the Expert Consensus Development Working Group for Neurobrucellosis. Following rigorous methodologies for clinical practice guideline and consensus formulation, Expert consensus on the diagnosis and treatment of neurobrucellosis (2025 edition) was developed. This consensus outlines 12 recommendations in 9 aspects: epidemiological history, clinical manifestations, cerebrospinal fluid analysis, immunological testing, pathogen identification, imaging and electrophysiological assessments, diagnosis and differential diagnosis, therapeutic strategies, and prognostic evaluation. Based on these recommendations, the diagnostic criteria and diagnosis and treatment process for Chinese neuroblastoma have been developed.

A Comprehensive Review of Antinutrients in Plant-Based Foods and Their Key Ingredients.

In recent years, the growing popularity of vegan and vegetarian diets, along with the rising demand for plant-based foods, has led researchers to concentrate on examining the presence and effects of antinutrients. While there are existing literature reviews focusing on antinutritional compounds, particularly on their reduction, this review aims to provide a comprehensive description of antinutrients for producers, food scientists, professionals, legislators and consumers, emphasising the complexity of the subject and the necessity for diverse approaches while identifying aspects that still require further research. Antinutrients, including protease inhibitors, amylase inhibitors, phytic acid, lectins, saponins, tannins, cyanogenic glycosides, oxalic acid, polyphenols, goitrogens and pyrimidine glycosides, are described, encompassing various aspects such as their structural characteristics, analytical detection methods, distribution, physiological impacts and strategies for mitigation or elimination. Specifically, our review concentrates on assessing the presence of antinutrients in plant-based food products and the primary ingredients, categorised into five distinct groups, cereals, pseudocereals, pulses, seeds and nuts, which are commonly used in their production. Among these categories, legumes are identified as the richest source of anti-nutritional compounds, followed by cereal grains. However, certain pseudocereals, seeds and nuts also demonstrate high levels of specific antinutrients. While antinutrients are generally regarded as harmful to nutrient absorption, recent studies have revealed some potential health benefits associated with them. Therefore, further invivo research is essential to elucidate the behaviour of antinutritional compounds within the human body. Additionally, there is a significant lack of formal regulations and guidelines regarding antinutrients, and food products currently do not feature labelling related to these compounds.

Diagnosis, screening, and follow-up of patients with familial interstitial lung disease: Results from an international survey

BackgroundAdvances in the field of genetics of interstitial lung diseases (ILDs) have led to the recent consensus statements made by expert groups. International standards for genetic testing in ILD have not yet been established. We aimed to examine current real-world strategies employed by pulmonologists working with familial ILD.MethodsA panel of pulmonologists with expertise in ILD developed an international survey aimed at clinicians working with ILD. The survey consisted of 74 questions divided into eight topics: characteristics of respondents, diagnosis, screening of first-degree relatives, screening tools, genetic testing methods, lung transplantation, ethical concerns, and future needs.ResultsOverall, 237 pulmonologists from 50 countries participated. A family history of ILD was asked for by 91% of respondents while fewer asked for symptoms related to telomere disorders. Respondents stated that 59% had access to genetic testing, and 30% to a genetic multidisciplinary team (MDT). Many respondents were unaware of specific genetic testing methods. Pathogenic genetic variants were seen as a potential contraindication for lung transplantation in 6–8% of respondents. Genetic screening of relatives was supported by 80% of respondents who indicated insufficient evidence and a lack of formal guidelines for genetics and ILD. Only 16% had a standardized program.ConclusionMost pulmonologists ask for a family history of ILD and recommend genetic testing for ILD and screening in relatives but have limited knowledge of specific tests and access to genetic MDT. Evidence-based guidelines to inform patients, relatives, and physicians are still warranted.

A Review of the Safety and Efficacy of Deucravacitinib for Plaque Psoriasis: An Expert Consensus Panel.

Psoriasis is a chronic, inflammatory disease associated with numerous negative physical and psychosocial impacts. Deucravacitinib is a novel, selective TYK2 inhibitor approved by the FDA for the treatment of moderate-to-severe plaque psoriasis in adults. Deucravacitinib has established efficacy and safety through several clinical trials, but many clinicians are unfamiliar with its safety profile given the lack of formal guidelines. Thus, this expert consensus panel aims to provide clinical recommendations on the efficacy, safety, and appropriate laboratory monitoring for deucravacitinib. A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the efficacy and safety of deucravacitinib. A panel of 10 dermatologists with expertise in managing psoriasis reviewed the relevant literature and crafted consensus statements regarding the efficacy, safety, and recommended laboratory monitoring for deucravacitinib. Using a modified Delphi process, each statement received supermajority approval and was assigned a strength of recommendation using the Strength of Recommendation Taxonomy (SORT) criteria. The literature search resulted in 101 articles that met search criteria. After screening the articles for relevance to the discussion topic, 14 articles were selected and distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 6 consensus statements and recommendations, 5 of which were given a strength of "A," 0 were given a strength of "B," and 1 was given a strength of "C." Deucravacitinib is an effective treatment for plaque psoriasis that is well-tolerated and has an excellent safety profile. The 6 consensus statements created by the panel provide expert recommendations regarding the efficacy, safety, and appropriate laboratory monitoring for deucravacitinib. The expert panel also concludes that deucravacitinib has a superior safety profile to traditional JAK inhibitors. After reviewing the clinical trials, the panel did not find evidence of a causal role for deucravacitinib in inducing laboratory abnormalities and did not recommend baseline and ongoing laboratory monitoring for patients treated with deucravacitinib. J Drugs Dermatol. 2025;24(2):147-155. doi:10.36849/JDD.8616.

Self-perceived knowledge, influencing factors and proposed educational interventions for diagnostic stewardship in the microbiology laboratory: The experience of Irish paediatric doctors.

Lab users should display an understanding of microbiology tests and avoid inappropriate requests which may yield negative clinical consequences. Our research addressed diagnostic stewardship education and the perspectives of paediatric hospital doctors on their (1) self-perceived knowledge, (2) motivators for test ordering, (3) proposed educational interventions and (4) preferred teaching modalities. An anonymous, mixed-methods, 34-item online questionnaire was distributed to paediatric doctors across three Irish hospital sites from March to May 2023. Descriptive statistics summarised Likert-scale responses and inductive thematic analysis was used to analyse open-ended items. Subgroup analyses examined differences between consultants and non-consultant hospital doctors (NCHDs). The analysis included 100 respondents (n = 45 consultants, n = 55 NCHDs, 24% response rate). Consultants scored higher than NCHDs in self-perceived knowledge (p < 0.001). Patient comorbidity, clinical status, local guidelines and accuracy of microbiological tests were the strongest motivators for test-ordering. Consultants were more likely to be influenced by accuracy (p = 0.03), costs (p = 0.01) and laboratory workload (p = 0.01). Only 27% reported formal teaching on diagnostic stewardship. NCHDs demonstrated increased willingness to engage in educational interventions (p = 0.024), and a comparatively higher interest in in-person teaching (p = 0.002) and gamification (p = 0.02). Respondents indicated a preference for formal guidelines on microbiology testing, in-person teaching, cost familiarisation and e-learning modules. Novel methods (peer-to-peer programmes, simulation and gamification) were less favoured. Dominant themes included; collaborative learning, increased microbiology presence, accessibility to education, barriers and administrative issues. Formal diagnostic stewardship educational programmes should be integrated into post-graduate curriculums for both NCHDs and consultants. Focuses for educational interventions include; development of local diagnostic stewardship guidelines, teaching on the cost and accuracy of microbiology tests, senior supervision and role-modelling.

The Impact of Selected Comorbidities on the Necessity for Physiotherapy in Patients Hospitalised with COVID-19

Abstract Data from 5173 patients hospitalized for COVID-19 at the University Hospital of Ostrava (UHO) between March 2020 and December 2021 were analysed in this retrospective study. The research aimed to find out whether the comorbidities being present increased the need for acute rehabilitation during COVID-19 hospitalization. Data were examined using descriptive statistics, Spearman's correlation coefficient, and binomial logistic regression. Among the total patient cohort (n = 5173), 27% required rehabilitation (RHB). The average age of patients was 64.9 ± 16.9 years, with rehabilitation durations ranging from 1 to 102 days. Of the rehabilitated patients, 92% (n = 1302) had hospital stays from 1 to 15 days, while 8% (n = 114) stayed more than 15 days. Patients had a median of 4 diagnoses each, with approximately one-fifth having more than six diagnoses. A weak but statistically significant positive association was observed for the length of rehabilitation and the number of diagnoses (Spearman’s correlation coefficient rs = 0.24). Adjusted statistical analysis revealed that patients with concomitant neurological conditions (G62, G81 according to ICD-10) (OR = 8.4; 95% CI 4.82–14.67) and certain respiratory diseases had the highest likelihood of requiring rehabilitation during their COVID-19 hospitalization. Additionally, patients with obesity were approximately 1.4 times more likely to need RHB than non-obese patients. The need for rehabilitation increased with the number of comorbidities, with the greatest need connected with neurological diagnosis. In light of these findings, more effective strategies for diagnosis, treatment and prevention can be developed for future epidemics or pandemics. It is imperative to reinforce health recommendations. The analysis of data enables the formulation of evidence-based public health guidelines that can serve as the foundation for a prompt and effective response in the event of another pandemic.

Subtitling the Sacred: Navigating Strategies and Challenges in Subtitling Religious Content

Subtitling religious content, particularly sacred texts, presents complex challenges within audiovisual translation, requiring a careful balance between linguistic fidelity, cultural sensitivity, and technical constraints. This study explores the hurdles faced by subtitlers when working with religious material and examines the strategies they employ to navigate these challenges. A survey was conducted to gather insights into the nuanced practices of subtitlers across various audiovisual genres. The survey was distributed via professional networks on Facebook, targeting specialised groups with memberships ranging from 10,000 to over 100,000, and through direct outreach on LinkedIn. Despite efforts to encourage participation through anonymity, the response rate was limited, with only 28 subtitlers completing the survey. The findings reveal that subtitlers prioritise linguistic accuracy while employing strategies such as literal translation, compensation, transposition, and omission to handle the complexities of religious content. Participants identified challenges in preserving meaning and addressing culturally or theologically sensitive material. These challenges are classified into intrinsic factors, such as the theological and linguistic nuances of the source text, and external influences, including technical constraints, media platforms, media genre, censorship policies, audience perspectives, and subtitlers’ own perspectives. Moreover, the study highlights a significant gap in formal guidelines for subtitling religious content, leaving subtitlers to rely heavily on their professional judgement, expertise, and personal discretion. This research offers valuable insights that can inform the development of specialised training and standardised practices in this critical yet underexplored field of audiovisual translation.

Associations between disease severity, depression, health-related quality of life, and physical activity in adults with sickle cell disease

BackgroundIndividuals with sickle cell disease (SCD) are faced with a plethora of challenges that affect their quality of life, mood, and physical and social participation. Physical activity (PA) is known to reduce inflammatory activity and enhance psychosocial health in individuals with chronic illnesses; however, there exist controversies on the role of PA in disease severity (DS), depression, and health-related quality of life (HRQoL) in SCD.ObjectiveThis study aimed to assess the role of PA in the level of DS, depression, and HRQoL in SCD and investigate mediation models among DS, depression, HRQoL, and PA in adults with SCD.MethodsA total of 385 patients with SCD (mean age 35.45 ± 12.01 years; 51.70% female) attending hematology clinics in two Nigerian tertiary hospitals participated in this cross-sectional study. Data on DS, depression, HRQoL, and PA were assessed through modified disease severity scoring protocol, patient health questionnaire-9, 12-item short-form health survey, and international physical activity questionnaire short-form, respectively. Multiple hierarchical regression and mediation analyses were applied.ResultsThe findings show that 53.5% are physically inactive, and PA accounts for 27.50%, 18.40%, 38.80%, and 8.50% of the variance observed in DS, depression, and physical component summary (PCS-12) and mental component summary (MCS-12) of HRQoL, respectively. There was a significant mediating role of DS in the relationship between PA and depression (β = − 0.0026; LLCI − 0.0031; ULCI − 0.0022), PCS-12 (β = 0.0019; LLCI 0.0013; ULCI 0.0024), and MCS-12 (β = 0.0009; LLCI 0.0001; ULCI 0.0018). The relationship between DS and depression was mediated only through PCS-12 (β = 0.2975; LLCI 0.1825; ULCI 0.4066). Similarly, only PCS-12 significantly mediated the relationship between PA and depression (β = − 0.0021; LLCI − 0.0026; ULCI − 0.0017).ConclusionIndividuals with SCD with high levels of PA have low levels of DS and symptoms of depression and reported better HRQoL. Furthermore, patients with better HRQoL, especially physical health showed low depressive symptoms in adults with SCD. Clinicians and policymakers should consider incorporating PA assessments and interventions into the care of patients with SCD. The formulation of specific PA guidelines for patients with SCD is also warranted.

Formal guidelines from an expert panel: intensive care unit medical staffing, organisation and working hours to improve quality of life at work in France

BackgroundIntensive care units (ICU) are characterized by high medical assistance costs and great complexity. Recommendations to determine the needs of medical staff are scarce, generating appreciable variability. The French Intensive Care Society (FICS) and the French National Council of Intensive Care Medicine (CNP MIR, Conseil National Professionel de Médecine Intensive Réanimation) have established a technical committee of experts, the purposes of which were to draft recommendations regarding staffing needs in ICUs and to propose optimal organisation of work hours, a key objective being improved workplace quality of life.ResultsLiterature analysis was conducted according to the GRADE methodology (Grade of Recommendation Assessment, Development and Evaluation). The synthesis work of the experts according to the GRADE method led to the development of 22 recommendations in 6 field. The experts issued a strong recommendation associated with a high level of evidence which is that work organization be given priority during periods of permanent care, with a maximum 16 h of consecutive work permitted. For 21 other recommendations, the level of evidence did not allow GRADE classification, and led to the formulation of expert opinions. All recommendations and expert opinions were validated (strong agreement).ConclusionThe work in the intensive care unit and in the intermediate intensive care unit is multifaceted, both clinical and non-clinical, and must include at least the following continuity and quality for patient safety. This document provides a detailed framework to propose an optimal medical staff.

Pentingnya SOP dalam Meningkatkan Kualitas Pelayanan Ketatausahaan di Sekolah Dasar

Standard Operating Procedures (SOPs) have an important role in creating information transparency, improving work efficiency, minimizing errors, and supporting the development of educators and education personnel's skills. This study uses a qualitative descriptive approach. The data used came from literature studies, direct observations, and interviews with administrative staff and teachers involved in school operations. The analysis process includes data reduction, data presentation, and conclusion drawing. The results of the analysis show that one of the components in managing administration in elementary schools to ensure the sustainability and quality of education is the Standard Operating Procedures or SOPs. Thus, a well-designed SOP is able to create information transparency, improve work efficiency, minimize errors, and support the development of the skills of educators and education personnel. The implementation of SOPs at SD IT Rocha Indonesia shows that although formal SOPs have not been fully implemented, initial steps such as digitization of archives, regular evaluations, staff training, and internal audits have supported more structured administrative management. Constraints such as technological limitations, manual attendance systems, and lack of formal guidelines can be overcome through the development of relevant SOPs and systematic implementation

A novel tool for assessing pediatric emergency care in low- and middle-income countries: a pilot study

BackgroundGlobally, most children seek emergency care at general rather than specialized pediatric emergency departments. There remains significant variation in the provision of pediatric emergency care, particularly in resource-constrained settings. The objective of this study is to pilot a self-assessment tool to evaluate pediatric emergency care capabilities in low- and middle-income country (LMIC) hospitals on the African Continent.MethodsThis was a prospective cross-sectional descriptive study using a convenience sample of sub-Saharan African hospitals. The assessment tool was developed by operationalizing the technical contents of existing standards and guidelines from international bodies including the World Health Organization and International Federation of Emergency Medicine. The pilot was conducted at emergency departments located across different regions on the African continent. Descriptive statistics were used to evaluate different domains of pediatric emergency care capabilities including pediatric triage, protocols, staffing, training, equipment, consumables, and medicines.ResultsSixteen hospitals with emergency departments completed the assessment tool (participation rate of 76%). The hospitals were in nine different countries across four regions of sub-Saharan Africa. National/academic hospitals comprised 56.3% of the participating hospitals. The majority, 44%, of these hospitals saw pediatric patient volumes of 2,000–4,999 patients per year. Dedicated pediatric triage spaces and resuscitation spaces were available at 37.5% and 56.3%, respectively. Formal pediatric resuscitation guidelines were used at 62.5%. Doctors on the self-assessment teams came from primarily pediatrics and general practitioner training backgrounds (both 68.8%). Basic respiratory and airway support equipment (e.g. oxygen, bag-valve mask devices) were available in all participating hospitals, whereas advanced airway equipment (e.g. pediatric intubation equipment) was available in 37.5% of hospitals. Most medicines from the World Health Organization Essential Medicines list were available at participating hospitals.ConclusionsTo date, this is the first assessment tool dedicated to the comprehensive evaluation of pediatric emergency care in LMICs. This pilot provides a first approach to evaluate pediatric emergency healthcare capabilities in the hospital setting with future directions to improve the tool based on qualitative feedback.

Quadratic Forms in Random Matrices with Applications in Spectrum Sensing.

Quadratic forms with random kernel matrices are ubiquitous in applications of multivariate statistics, ranging from signal processing to time series analysis, biomedical systems design, wireless communications performance analysis, and other fields. Their statistical characterization is crucial to both design guideline formulation and efficient computation of performance indices. To this end, random matrix theory can be successfully exploited. In particular, recent advancements in spectral characterization of finite-dimensional random matrices from the so-called polynomial ensembles allow for the analysis of several scenarios of interest in wireless communications and signal processing. In this work, we focus on the characterization of quadratic forms in unit-norm vectors, with unitarily invariant random kernel matrices, and we also provide some approximate but numerically accurate results concerning a non-unitarily invariant kernel matrix. Simulations are run with reference to a peculiar application scenario, the so-called spectrum sensing for wireless communications. Closed-form expressions for the moment generating function of the quadratic forms of interest are provided; this will pave the way to an analytical performance analysis of some spectrum sensing schemes, and will potentially assist in the rate analysis of some multi-antenna systems.

Development of an Adaptable Qualification Test Set for Personnel Involved in Visual Inspection Procedures of Parenteral Drug Products Manufactured Under Good Manufacturing Practice Conditions in Hospital Pharmacy Compounding Facilities.

Objectives: Parenteral drug products manufactured under GMP conditions should be visually inspected for defects and particulate contamination by trained and qualified personnel. Although personnel qualification is required, no practical protocols or formal guidelines are available for the development of qualification test sets (QTSs) used for qualification procedures. The current practice is to either procure a standardized QTS from a commercial supplier or amass sufficient manufacturing rejects during visual inspection procedures to compile in-house QTSs. However, both strategies inherently possess disadvantages and limitations. The objective of this study was to develop a manufacturing protocol for an optimal and adaptable QTS for training and qualification procedures. Methods: We combined the results of a literature search, survey of five Dutch hospital pharmacy compounding facilities, semi-structured personnel interviews, and extensive pre-GMP formulation studies to develop an optimal and adaptable QTS manufacturing protocol. Results: The literature search did not identify a manufacturing protocol for an optimal and adaptable QTS, but did identify specifications and requirements for optimal QTSs. The survey among hospital pharmacy compounding facilities revealed considerable variability in the qualification procedures and used QTSs. Semi-structured personnel interviews and pre-GMP formulation studies demonstrated that defects encountered during routine productions could be realistically simulated with pharmaceutical-grade excipients. As a proof-of-concept, we manufactured two different QTSs under GMP conditions and assessed these for formal GMP training and qualification purposes, which were considered a significant improvement compared to using manufacturing rejects. Conclusions: To the best of our knowledge, this is the first study presenting these data and our adaptable protocol, which is provided in the Supplemental Materials, may aid compounding facilities in the standardization, training, and qualification of personnel involved in visual inspection procedures.

Pipeline esophageal varices: Insights from clinical cases and models.

While esophageal varices (EVs) are typically treated endoscopically, other options such as interventional radiology or surgical treatment are considered when endoscopic treatment is challenging. Pipeline EVs are difficult to treat endoscopically due to their large diameter, and currently, no specific treatment guidelines have been established. We reviewed cases of pipeline EVs treated at our hospital and analyzed previously reported cases to collect evidence for the formulation of treatment guidelines. Additionally, we created EV simple models to evaluate the safety margin of endoscopic variceal ligation for varices. Our analysis included 14 cases of pipeline EVs (four cases treated at our hospital from 2013 to 2024 and 10 previously reported cases from 1990 to 2024). Endoscopic treatment alone was insufficient in six cases (42.9%), and five cases (35.7%) required interventional radiology or surgical intervention. Using EV simple models with varying diameters, EVL was inadequate for varices with diameters of 20mm or larger. There are few reported cases of pipeline EVs, making it difficult to determine a treatment algorithm. In our study using an EV simple model, it was suggested that endoscopic variceal ligation is effective in blocking blood flow for EVs with a diameter of 15mm or less. It is important that we understand there are EVs, such as pipeline EVs, for which there are limitations to safely occluding blood flow with endoscopic variceal ligation, and it may be necessary to develop treatment strategies that include methods other than endoscopic therapy.

Home intravenous diuretic administration for heart failure management: A scoping review.

Heart failure (HF) significantly impacts healthcare systems due to high rates of hospital bed utilization and readmission rates. Chronic HF often leads to frequent hospitalizations due to recurrent exacerbations and a decline in patient health status. Intravenous (IV) diuretic administration is essential for treating worsening HF. Emerging strategies include home-based IV diuretic therapy administration; however, limited practical implementation guidance is available. This scoping review aims to summarize the literature on home IV diuretic administration for HF patients, focusing on the interventions' characteristics, and facilitators and barriers to its implementation. This review followed the scoping review framework proposed by Arksey and O'Malley and PRIMSA-ScR. A comprehensive search was conducted across six databases (CINAHL, the Cochrane Library, EMBASE, MEDLINE, PsychINFO and Scopus) and grey literature to identify English studies from inception to April 13, 2024. Two independent reviewers screened articles and resources for inclusion and data was extracted using a form created by the authors in Covidence. The search yielded 2,049 results, with nine studies meeting the inclusion criteria. Studies varied in design, including feasibility, pilot, observational, and pre/post-intervention evaluations. The majority were conducted in European countries, with sample sizes ranging from 12 to 96 patients receiving home IV diuretics for HF. Key implementation challenges include appropriate patient selection, IV cannulation competency of healthcare providers, and multi-disciplinary and multi-agency collaboration. Evidence on home IV diuretic administration practices for HF management remains limited. However, this scoping review suggests that commonalities across studies could form the basis for developing standard protocols in outpatient settings. Despite the lack of formal evidence-based guidelines, the findings also suggest that tailored, community-specific approaches and safe infusion guidance documents could enhance the efficacy and scalability of home IV diuretic therapy. Future research should focus on refining these strategies and exploring diuretic escalation methods beyond traditional acute care administration to optimize patient outcomes.

Clinical Outcomes in Diabetic Females Presenting with STEMI: A Cohort Study

Introduction: Although the incidence of Acute Coronary Syndrome (ACS) is lower in women, outcomes are worse, particularly in diabetic females. Despite advances in revascularisation and treatment, mortality rates among diabetic females remain higher, with poorer postpercutaneous coronary intervention outcomes. Studies have rarely addressed the differences in the course of myocardial infarction in diabetic females and this underrepresentation has influenced the formulation of guidelines. Aim: To evaluate the in-hospital composite outcomes of death, non fatal myocardial infarction, emergency revascularisation, heart failure and cerebrovascular accident in diabetic women presenting with ST Elevation Myocardial Infarction (STEMI), as well as the individual in-hospital outcomes and outcomes at one and three months follow-up. Materials and Methods: This was a prospective single-centre cohort study conducted between November 2017 and October 2018 on 204 patients with STEMI and followed-up for three months. Data were collected from patients using a semistructured questionnaire-based interview, clinical examination, laboratory investigations, echocardiography and angiography. In-hospital outcomes—death, non fatal MI, emergency revascularisation, heart failure and cerebrovascular accident—were studied. Telephonic follow-up was conducted at one and three months. The comparison of variables was carried out using the Independent Student’s t-test or Chi-square test, and regression analysis was performed to identify predictors of mortality. Results: The mean age was 64±11 years; 60.3% were hypertensive and 26% had dyslipidaemia. A total of 12.3% were newly diagnosed diabetics. The mean prehospital delay was 201.9±156.8 minutes. Primary angioplasty was performed in 77%, while thrombolysis was done in 16.7%. The composite outcome was observed in 26.3% of the patients, with heart failure occurring in 19%, cardiogenic shock in 27.9% and death in 16.2%. Cerebrovascular accidents were noted in 0.5% and renal dysfunction was present in 13.2%. At one and three months, heart failure occurred in 7.6% and 5.8%, respectively. Among those with in-hospital mortality, a higher proportion had Anterior Wall Myocardial Infarction (AWMI) (p=0.043), were in Killip class&gt;II (p-value &lt;0.0001), and had qRBBB (Right Bundle Branch Block) (p-value &lt;0.0001). They presented later, with higher blood sugar (p-value &lt;0.0001) and creatinine values (p-value=0.009) and had a lower Ejection Fraction (EF) (p-value=0.003). Killip class (OR=16.0), presence of Ventricular Septal Rupture (VSR) (OR=23.4), no-reflow phenomenon (OR=23.4) and development of renal dysfunction (OR=9.0) were identified as predictors of mortality. Conclusion: Despite a high rate of revascularisation and fewer procedure-related complications, outcomes remain grim, with a higher incidence of heart failure, cardiogenic shock, renal dysfunction and mortality. A worse clinical profile, left ventricular dysfunction and renal dysfunction were significant predictors of mortality

A roadmap for assessing the diagnostic usefulness of neurosensory testing and an updated method for exposure assessment among vibration-exposed workers in northern Sweden

ABSTRACT Workers who use handheld vibrating machines such as grinders, hammers and chainsaws expose themselves to hand-arm vibration (HAV). Exposure to HAV may cause injuries to both the neurological and the vascular system. The occupational health services (OHS) in Sweden use a formal guideline for secondary prevention focusing on early detection of vibration-related injuries. The guide includes several screening tools, such as a screening questionnaire, clinical examinations, and laboratory tests. There are no studies, to our knowledge, on the diagnostic value of the separate items on symptoms in the screening questionnaire in relation to the laboratory tests or the clinical examinations performed during a medical examination among patients exposed to HAV. Furthermore, the recently presented ISO standard for HAV measurements (ISO/TR 18,750) has only been tested for vascular injuries and not neurological injuries. This research roadmap aims to evaluate separate items in a screening questionnaire on neurological symptoms in relation to laboratory and clinical tests among HAV exposed workers in the Arctic region of Northern Sweden. It also covers a comparison of the dose-response of the current ISO 5349–1 measurement standard and the new suggested standard ISO/TR 18,750 with the neurosensory outcomes. This manuscript describes the study rationale, design, methods, and significance.