Search Results (118)

Medication-related harm remains a major patient-safety challenge, substantially driven by fragmented pharmacovigilance ecosystems, inconsistent drug nomenclature, heterogeneous interaction knowledge bases, and the absence of unified multimodal medication-safety infrastructures. Existing clinical decision-support systems frequently remain interaction-centered, with limited integration of complementary safety domains such as lactation risk assessment, intravenous compatibility evaluation, and regulatory toxicity overlays. This study aimed to develop and evaluate SafeRx, a provenance-aware pharmaceutical knowledge integration platform designed to harmonize heterogeneous medication-safety data within a unified canonical framework. SafeRx integrated Romanian regulatory product summaries, Danish drug–drug interaction repositories, OpenFDA boxed warning datasets, LactMed lactation safety records, and Stabilis intravenous compatibility data through automated extraction pipelines, ontology-aware canonical substance normalization, AI-assisted semantic enrichment, and pharmacist-supervised governance workflows. The platform consolidated 2190 canonical substances linked to 9463 validated identifier mappings, 9932 canonical interaction pairs enriched with tier-based prioritization and mechanism-aware annotations, 514 regulatory boxed warning records, 1895 lactation safety entries, and 9088 intravenous compatibility records. SafeRx demonstrates the feasibility of constructing an interoperable, explainable, and pharmacist-supervised medication-safety infrastructure capable of integrating heterogeneous regulatory, pharmacologic, reproductive, and physicochemical safety domains within a unified clinically navigable framework for research, pharmacovigilance, and clinical decision-support applications. Future studies should evaluate prospective clinical implementation, electronic health record interoperability, and the real-world impact of tier-based prioritization on prescribing workflows, alert fatigue, and medication-safety outcomes. Full article

Background: Voluntary Assisted Dying (VAD) legislation in Western Australia (WA) introduced new responsibilities for community pharmacists, including the safe disposal of unused VAD substances. Pharmacists may receive VAD-related enquiries; however, their preparedness, including their knowledge of VAD, remains largely unexplored. Aim: To explore Western Australian community pharmacists’ knowledge of VAD and their role as Authorised Disposers under the Voluntary Assisted Dying Act 2019 (WA). Methods: Community pharmacists in WA were invited to participate in an anonymous, online survey consisting of multiple choice and open-ended questions. Results: Of 143 respondents, 76% were aware that VAD is an end-of-life option; despite this, 64% were uncertain about its relevance to their role. Almost one-third had received VAD-related enquiries. Of these, 40% could not provide information, with half attributing this to insufficient knowledge. Among those yet to receive a VAD-related enquiry (n = 115), 75% felt ‘not confident’ to respond, with 76% attributing this to lack of knowledge. A total of 63% of participants were unaware that they may be requested to perform authorised disposal. Uncertainty surrounding the process and the legal and ethical aspects were frequently mentioned. Conclusion: WA Community pharmacists demonstrate awareness of VAD legislation but have gaps in knowledge, particularly regarding authorised disposal. Further training and resources are essential. Full article

Background/Objectives: Artificial intelligence (AI) is increasingly used in clinical decision-support systems, yet its adoption in low- and middle-income countries, including Jordan, remains limited and underexplored. Understanding how healthcare professionals perceive AI-assisted clinical decision-making is essential for safe and contextually appropriate implementation. This study explored healthcare professionals’ perceptions of AI-assisted clinical decision-making in Jordan, with particular attention to trust, accuracy, accountability, professional judgement, digital literacy, and health-system readiness. Medication-related safety and prescribing concerns were examined as secondary cross-cutting issues where they emerged from participants’ accounts. Methods: A qualitative study was conducted using semi-structured, in-depth interviews with 22 purposively sampled healthcare professionals from public, private, and university-affiliated healthcare institutions in Amman, Irbid, and Zarqa. Participants included physicians, nurses, pharmacists, and allied health professionals with varied specialties and levels of seniority. Data were analysed using Braun and Clarke’s reflexive thematic analysis. Member checking, peer debriefing, reflexive memos, and audit trails were used to enhance trustworthiness, and reporting followed the Consolidated Criteria for Reporting Qualitative Research (COREQ). Results: Eight overarching themes were identified: conditional trust in AI-assisted clinical decision-making; concerns regarding accuracy and confident algorithmic errors; accountability and professional responsibility; AI as an adjunct rather than a substitute for clinical judgement; the influence of experience, specialty, and digital literacy on AI acceptance; Jordanian health-system readiness; privacy, confidentiality, and algorithmic bias; and training requirements for safe AI use. Medication-related safety emerged as a cross-cutting concern, particularly in relation to dosing, polypharmacy, drug–drug and drug–herb interactions, and the risk of over-reliance on AI-generated recommendations. Conclusions: Healthcare professionals in Jordan expressed cautious but constructive views toward AI-assisted clinical decision-making. AI was perceived as potentially useful when used to support, rather than replace, professional judgement. Participants’ accounts suggest that safe implementation depends on local validation, clear accountability frameworks, ethical data governance, interprofessional training, and careful consideration of medication-safety expertise where AI tools influence prescribing or therapeutic decisions. These findings highlight the importance of context-sensitive AI governance strategies that support trustworthy, accountable, and professionally supervised AI adoption in healthcare. Full article

Background/Objectives: Upper respiratory tract infections (URTIs), including common cold and influenza, remain a major global health burden, and their symptomatic management often includes the use of herbal medicines alongside conventional therapies. The aim of this study was to evaluate the real-world use of herbal medicines as drug candidates in the management of URTIs in Estonia, with a focus on differences between pharmacy customers and pharmacy professionals. Methods: A cross-sectional survey was conducted among 905 participants, including 400 pharmacy customers and 505 pharmacy professionals (pharmacists and pharmacy assistants). Standardized questionnaires were used to assess the frequency of use, perceived effectiveness, and safety considerations of commonly used herbal substances and home remedies in adults and children. Results: Herbal medicines and home remedies were widely used, reported by 68% (95% CI: 63.4–72.6%) of pharmacy customers and 71% (95% CI: 67.0–75.0%) of pharmacy professionals. The most commonly used herbal substances included lemon (79%), ginger (57%), garlic (56%), raspberry (55%), and chamomile (50%). While most respondents perceived these remedies as effective for symptom relief, notable discrepancies were observed between customer and professional assessments of efficacy. The use of several herbal substances in children did not consistently align with European Medicines Agency recommendations, highlighting potential safety concerns. The findings demonstrate that widely used herbal substances represent real-world candidates for supportive URTI management; however, their perceived effectiveness and patterns of use are not always supported by regulatory guidance or clinical evidence. These results underscore the need for further pharmacological and clinical studies, as well as improved evidence-based communication between healthcare professionals and patients. Conclusions: The results allow the identification and prioritization of herbal substances as real-world drug candidates for further pharmacological and clinical development. Full article

The usefulness of ChatGPT, a large language model, has recently been explored in medical research. However, no studies have examined its reproducibility or applicability to therapeutic drug monitoring (TDM), a core task of clinical pharmacists. In this simulation study, we evaluated the feasibility of using ChatGPT for vancomycin (VCM) TDM based on Bayesian estimation. A total of 1000 virtual patients were generated by Monte Carlo simulations using a population pharmacokinetic model of VCM. Bayesian-estimated pharmacokinetic parameters and predicted concentrations were input into ChatGPT, and dosage regimens were compared among the three conditions, using temperature as a hyperparameter (T = 0.1, 0.5, and 1.0). Reproducibility was evaluated using the mode percentage in repeated runs. The reproducibility of the ChatGPT output was higher at T = 0.1 than at T = 0.5 and T = 1.0. When ChatGPT simulated the mode-recommended regimen (T = 0.1), the target attainment rate of the area under the serum concentration (AUC) (400–600 mg·h/L) improved from 25.5% (pre-optimization AUC (fixed-dose regimen)) to 71.5% (post-optimization AUC (ChatGPT-guided regimen)). These findings demonstrate that ChatGPT-based TDM using Bayesian estimation can enhance dose optimization. Adjusting the hyperparameter temperature to 0.1 improved reproducibility, suggesting that a reliable ChatGPT-assisted TDM support system may be clinically useful. Full article

Objectives: Medication adherence in elderly patients is shaped by cognitive, behavioral, systemic, and socioeconomic factors. This review aimed to identify determinants and effective strategies to improve adherence in older adults. Methods: A systematic search of PubMed, Scopus, and ScienceDirect (2015–2025) followed PRISMA 2020 guidelines. From 5116 records, 53 studies met inclusion criteria. Randomized controlled trials were meta-analyzed using standardized mean differences under a random-effects model. Risk of bias in the 10 pooled trials was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE framework. Results: Adherence ranged from 25.3% in institutionalized patients to 97.6% in pharmacist-led schizophrenia programs. Cognitive impairment and frailty reduced adherence (54.2%), while caregiver involvement improved rates, especially in dementia and schizophrenia (77.4–97.6%). Socioeconomic barriers, including medication cost, contributed to nonadherence but were mitigated by subsidies. Digital tools enhanced adherence in chronic disease, and machine learning models accurately predicted nonadherence (AUC up to 0.935). Effective interventions—caregiver support, digital platforms, and single-pill regimens—increased adherence by 25–59% and reduced cardiovascular events. The meta-analysis demonstrated a significant pooled effect (Standardized Mean Difference, SMD = 0.71, 95% CI: 0.11–1.54), although heterogeneity was high (I² = 99%). The RoB 2 assessment of the 10 pooled trials identified 2 at low risk, 4 with some concerns, and 4 at high risk of bias; the GRADE certainty of evidence was rated Very Low. Conclusions: Multiple factors, including frailty, cognitive deficits, socioeconomic barriers, regimen complexity, and the level of caregiver support, appear to be consistently associated with medication adherence in older adults. Strategies such as caregiver engagement, digital health tools, regimen simplification, and mental health support may contribute to improved adherence, although effect sizes vary considerably across study contexts. Given the substantial heterogeneity, Very Low certainty of evidence (GRADE), and variable study quality, findings should be interpreted with caution. System-level reforms, financial assistance programs, and culturally tailored approaches may further support adherence, while the successful implementation of digital health solutions will require addressing literacy, accessibility, and integration challenges. Full article

Background: Visual impairment (VI) describes decreased visual function that interferes with an individual’s ability to perform daily activities, such as reading, driving, and other executive tasks. Providing optimal pharmaceutical care for this population can be challenging for pharmacists, as individuals with VI face numerous obstacles in managing their medications. This study explores the challenges experienced by pharmacists and visually impaired patients and aims to compare their points of view to identify existing gaps and propose recommendations to optimize medication use among individuals with VI. Method: A cross-sectional study was conducted between September 2024 and January 2025 among pharmacists (n = 152) and visually impaired patients (n = 31) in the Qassim Region of Saudi Arabia. Pharmacists completed a self-administered questionnaire, while data from visually impaired patients were collected via structured face-to-face interviews. Data analysis was performed using IBM SPSS Version 21, with a significance level set at p < 0.05. Results: A total of 152 pharmacists and 31 visually impaired individuals participated in the study. Only 5.3% of pharmacists had received training related to VI care, and most counseling was directed to caregivers rather than patients (80.3%). pharmacists with additional training in VI were significantly more likely to employ unique or appropriate packaging methods (p < 0.001), and male pharmacists were more likely to rely on caregivers during OTC counseling (p = 0.014). Among the visually impaired participants, 77.5% reported difficulty reading medication packages and 67.7% faced challenges entering pharmacies. Braille literacy was significantly higher among males (p = 0.018) and those with higher education (p = 0.022). Overall, 90.3% expressed a need for improved accessibility tools and communication support in pharmacies. Conclusions: Pharmacists showed confidence in assisting visually impaired patients; however, most lacked formal training and relied heavily on caregivers for communication. Visually impaired individuals also reported difficulties accessing pharmacies, reading medication labels, and receiving complete information from pharmacists. Based on these findings, implementing specialized training programs, expanding Braille and tactile labeling, and integrating assistive technologies within pharmacies are recommended to improve safety and equitable medication use. Full article

Background: Burnout is a significant occupational risk among healthcare professionals, including community pharmacy staff, whose differing roles and responsibilities may influence burnout determinants. This study aimed to compare burnout levels and associated work characteristics between master pharmacists (MPs) and assistant pharmacists (APs) working in community pharmacies in Northeastern Bulgaria. Methods: A cross-sectional observational survey was conducted between November 2023 and December 2024 using an anonymous, self-administered online questionnaire completed by 221 MPs and 151 APs. Burnout was assessed using the Maslach Burnout Inventory—Human Services Survey for Medical Personnel, measuring emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). Work characteristics were evaluated using items adapted from an internationally recognized European Commission guideline on occupational health and safety risks in the healthcare sector. Results: High levels of EE and DP were observed in both groups, with no statistically significant differences in mean burnout scores. Age and years of professional experience were not significantly associated with burnout. However, work environment factors differed: poor team communication and a negative workplace climate affected both groups, whereas lack of recognition and support was more influential for MPs, and physical workload and frequent interruptions were more prominent stressors for APs. Conclusions: Burnout is prevalent among community pharmacy professionals, with role-specific organizational factors shaping its determinants and highlighting the need for targeted preventive strategies. Full article

Background/Objectives: Antimicrobial resistance (AMR) is considered a major threat by the healthcare community. In this context, the AWaRe (Access, Watch, Reserve) classification of antibiotics is a valuable tool that can assist physicians during the clinical decision process and pharmacists in promoting the rational use of antibiotics. Pharmacovigilance studies based on real-world evidence offer valuable insight into the AMR phenomenon. The aim of this study was the assessment of the resistance, ineffectiveness, and off-label use signals of all five cephalosporins belonging to the Reserve group (ceftazidime/avibactam, ceftaroline, cetolozane/tazobactam, ceftobiprole, and cefiderocol). Methods: The study was conducted using descriptive approaches on EudraVigilance data and disproportionality analyses comparing each of the fourteen cephalosporins in the Watch group. Results: Ceftazidime/avibactam (n = 904, 38.6%) topped the reports, followed by ceftaroline (n = 559, 23.9%) and ceftolazane/tazobactam (n = 560, 23.9%). The lowest number of reports was submitted for cefiderocol (n = 176, 7.5%) and ceftobiprole (n = 146, 6.2%). The resistance to ceftazidime/avibactam, cefiderocol, and ceftolozane/tazobactam was reported with a higher probability than all others, the strongest signal being observed for cefiderocol against cefixime (ROR: 171.25, 95% CI 79.64–368.27). All cephalosporins from the Reserve group (except ceftobiprole) have higher probability for reporting ineffectiveness than cephalosporins from the Watch group; the strongest signal was observed for cefiderocol–cefditoren (ROR: 14.70, 95% CI 6.73–32.11). All cephalosporines from the Reserve group had a higher probability of reporting off-label use by comparison with the ones from the Watch group, except for two cases of no disproportionate signal between cefiderocol–cefoperazone and cefiderocol–ceftizoxime; the strongest signal was observed for ceftolozane/tazobactam–cefotaxim (ROR: 43.61, 95% CI 30.14–63.09). Conclusions: This analysis supplements information from clinical trials and current clinical practice, underscoring the critical need for rigorous antibiotic stewardship programs. Notably, even restricted use of cephalosporins demonstrated therapeutic failure and inappropriate utilization. Full article

Opioid overdoses in the United States remain a significant public health concern. Opioid use disorder (OUD) is stigmatized, exacerbating negative health outcomes. Reducing stigma in healthcare, including in pharmacies, is critical. The “Let’s Talk Stigma” program was collaboratively developed with two schools of pharmacy, a local health department, and individuals with lived drug use experience. It aimed to reduce OUD-related stigma among pharmacists, pharmacy technicians, student pharmacists, and other allied health professionals. The program included six core components: a podcast, continuing education, a standardized curriculum for student pharmacists, training for pharmacy technicians and medical assistants, pharmacy outreach by student pharmacists, and partnerships with chain pharmacies. The anti-stigma podcast reached a global audience with nearly 22,000 listens, while local sessions engaged over 5000 individuals. These initiatives were integrated into Doctor of Pharmacy curricula, with student pharmacists distributing stigma-reduction kits in local pharmacies. A mixed-methods approach, incorporating qualitative data from participant reflections and quantitative data from surveys, podcast analytics, and attendance records, was used for program evaluation. Participants reported increased awareness of stigma, improved attitudes, and greater professional responsibility to reduce stigma. The program successfully leveraged partnerships, flexible delivery methods, and inclusion of people with lived drug use experience in its design. Full article

Background/Objectives: According to recent literature, the prevalence and incidence of long-term illnesses such as asthma and diabetes in young people have substantially risen over the past 13 years. Recent figures indicate that, in England, 4.10% of all prescriptions were prescribed for young people. The aim of this study was to investigate young people’s perspectives of pharmaceutical services provided by primary care pharmacists relating to medication. Methods: A cross-sectional survey using both online and paper-based tools was conducted from March to November 2019. The population for this survey was young people from 18 to 24 years old registered as students at one of the universities in England. The survey consisted of twenty-four questions, and they were a mix of closed-ended questions, such as multiple-choice and Likert scales, and open-ended questions. Results: A total of 210 out of 800 survey responses were completed from different recruitment sources, achieving a response rate of 26.25%. Most participants were female (62.38%), and the most frequent age was 18 years (35.24%). Among participants, 15.70% were diagnosed with long-term illnesses, of which 33.33% were reported as the respiratory disease, asthma. Pharmacists were not utilised as a source of information for young people, with the majority (60.60%) obtaining information from their doctors. Most of the participants (96.97%) had not taken part in a Medicines Use Review (MUR) or New Medicine Service (NMS), and 78.79% were not aware of any services or support groups by their pharmacist. Among different healthcare professionals, GPs and hospital doctors were the most frequently reported to discuss with young people about their illnesses. Conclusions: There is an opportunity to further develop pharmaceutical services and support by primary care pharmacists for young people with long-term illnesses. Policymakers and primary care pharmacists in the future could utilise the perceptions and opinions of young people found in the current study to inform the development of primary care pharmacy services to meet young people’s needs and perceptions. These results are of benefit to policymakers in assisting in the development of pharmacy services. Further research will enhance understanding of the perceptions of young people about the pharmaceutical services offered by primary care pharmacists with respect to medications. Full article

Background: Burnout is a common occupational health risk among healthcare professionals. While the phenomenon has been studied in physicians and nurses, limited evidence exists regarding pharmacists and public health inspectors despite their critical role in ensuring safe medication use and protecting population health. The study aims to identify and analyze the influence of work environment characteristics on the level of professional burnout among master pharmacists, assistant pharmacists, and public health inspectors. Methods: A cross-sectional anonymous survey was conducted among 491 healthcare professionals (221 master pharmacists, 151 assistant pharmacists, and 119 public health inspectors). Burnout was assessed using the validated Maslach Burnout Inventory–Human Services Survey (MBI-HSS (MP)), covering three dimensions: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). Work environment characteristics were examined across four domains: work tasks, stressors, occupational risks, and social environment. Data were analyzed using descriptive statistics and chi-square tests with IBM SPSS. Results: High levels of EE (66.6%) and DP (53%) were reported, while low PA was less frequent (6.7%). Significant factors associated with EE included time constraints (χ² = 9.985; p < 0.01), workflow disruptions (χ² = 23.987; p < 0.001), insufficient information (χ² = 22.890; p < 0.001), and lack of recognition (χ² = 16.498; p < 0.001). The social environment demonstrated the broadest impact, influencing all three burnout dimensions. Conclusions: The study found a risk of professional burnout among the surveyed groups which is associated with modifiable work environment characteristics. Preventive interventions aimed at promoting a supportive work environment could help mitigate this risk. Full article

Introduction: Tuberculosis (TB) remains a public health concern, and people at risk for TB are hesitant to seek care. The first South African National TB prevalence survey, conducted in 2017–2019, found that most participants with TB symptoms did not seek care for TB. In 2022, an estimated 23% of people with TB in South Africa were undiagnosed, contributing to the country’s burden of “missing” TB cases. This study explores health-seeking behaviour among people with TB (PwTB) in South Africa, focussing on barriers and facilitators to care-seeking and the quantification of TB-related stigma from a patient and community perspective. Methods: We conducted a mixed-method study in the City of Johannesburg (COJ) Metropolitan Municipality from February to March 2022. PwTB aged 18 and older initiating TB treatment for microbiologically confirmed pulmonary TB were recruited from three primary healthcare facilities in the COJ. After providing written informed consent, they participated in a one-time, in-depth, face-to-face interview. The interviews were digitally recorded and conducted by trained facilitators. We used thematic analysis with deductive approaches to develop themes. We used the Van Rie TB stigma assessment scale to quantify perceived stigma. Results: We interviewed 23 PwTB with an overall median age of 39 years and 14 (61%) males. Patient-level barriers to accessing TB care included visiting traditional healers and pharmacists before their TB diagnosis; wrong or missed diagnosis by private doctors; work commitments; scarcity of resources to attend the clinic or walk long distances; perceived and experienced stigma; and a lack of TB knowledge. Facility-level barriers included long clinic queues and uncertainty about where to receive TB care in the clinic. Facilitators for TB care-seeking included being in contact with someone who had TB, receiving encouragement from family, or having knowledge about TB transmission and early diagnosis. The overall median total stigma score among 21 PwTB was 53 (IQR: 46–63), with median community and patient stigma scores of 25 (IQR: 22–30) and 31 (IQR: 21–36), respectively. Conclusions: We found important considerations for the TB programme to improve the uptake of services. Since PwTB consult elsewhere before visiting a facility for TB care, TB programmes could establish private–public partnerships. TB programmes could also increase TB awareness in the community, especially among males, and mobile clinics could be considered to assist with TB case detection and treatment provision. Applying behavioural design techniques and co-designing interventions with patients and providers could improve TB health-seeking behaviours. Full article

Background/Objectives: Smart Formulation is an artificial intelligence-based platform designed to predict the Beyond Use Dates (BUDs) of compounded oral solid dosage forms. The study aims to develop a decision-support tool for pharmacists by integrating molecular, formulation, and environmental parameters to assist in optimizing the stability of extemporaneous preparations. Methods: A tree ensemble regression model was trained using a curated dataset of 55 experimental BUD values collected from the Stabilis database. Each formulation was encoded with molecular descriptors, excipient composition, packaging type, and storage conditions. The model was implemented using the KNIME platform, allowing the integration of cheminformatics and machine learning workflows. After training, the model was used to predict BUDs for 3166 APIs under various formulation and storage scenarios. Results: The analysis revealed a significant impact of excipient type, number, and environmental conditions on API stability. APIs with lower LogP values generally exhibited greater stability, particularly when formulated with a single excipient. Excipients such as cellulose, silica, sucrose, and mannitol were associated with improved stability, whereas HPMC and lactose contributed to faster degradation. The use of two excipients instead of one frequently resulted in reduced BUDs, possibly due to moisture redistribution or phase separation effects. Conclusions: Smart Formulation represents a valuable contribution to computational pharmaceutics, bridging theoretical formulation design with practical compounding needs. The platform offers a scalable, cost-effective alternative to traditional stability testing and is already available for use by healthcare professionals. Its implementation in hospital and community pharmacies may help mitigate drug shortages, support formulation standardization, and improve patient care. Future developments will focus on real-time stability monitoring and adaptive learning for enhanced precision. Full article

Seronegative sicca syndrome encompasses patients who present with xerostomia and/or keratoconjunctivitis sicca but lack anti-SSA/SSB antibodies and do not fulfill current classification criteria for primary Sjögren’s syndrome (pSS). Despite symptom overlap with pSS, these individuals remain diagnostically and therapeutically unclassified. This review studies the clinical, immunological, and pathological spectrum of seronegative sicca, highlighting its heterogeneity and the limitations of antibody-centric diagnostic frameworks. Histopathologic findings in some seronegative patients—including focal lymphocytic sialadenitis—mirror those seen in pSS, suggesting underlying immune-mediated glandular damage. In others, nonspecific or normal biopsy findings suggest non-immune mechanisms. New evidence of immune activity, such as elevated cytokines (BAFF, IFN-α), and novel autoantibodies (SP-1, CA-VI), further supports the concept of subclinical autoimmunity in a subset of these patients. Clinically, they often face significant burden, including dryness, fatigue, and pain, yet remain excluded from most research cohorts, therapeutic trials, and clinical guidelines. Their management is often individualized, relying on symptomatic therapies rather than immunomodulatory agents. The lack of validated diagnostic criteria and prognostic markers compounds the uncertainty surrounding disease evolution, as some patients may later seroconvert or develop systemic features. To address these gaps, a paradigm shift is needed—one that embraces the spectrum of sicca syndromes, incorporates advanced immunophenotyping, and allows inclusion of seronegative patients in research and care algorithms. Full article