Search Results (437)

Background/Objectives: The body mass index (BMI) is considered a key method for the classification of individuals’ weight status, according to cut-off points proposed by the World Health Organization (WHO); however, the use of this classification is still the subject of debate and criticism. We aimed to evaluate the accuracy of the WHO BMI classification in reflecting true adiposity in the Italian general population. Methods: This cross-sectional study included 1351 adults of mixed gender aged between 18 and 98 years, comprising 19 (1.4%) underweight individuals, 787 (58.3%) normal weight, 354 (26.2%) overweight, and 191 (14.1%) with obesity according to the WHO BMI. After that they were re-categorized according to adiposity based on body fat percentage (BF%) measured by dual-energy X-ray absorptiometry (DXA). The agreement between the two classification systems was tested using the kappa statistic (κ), with the system based on BF% being considered the gold standard. Results: According to the BMI classification, 78.1% of the individuals who were in the normal weight range were correctly classified. However, 53.4% of the overweight group and 68.4% of the underweight group were misclassified according to the BMI, as the majority of those misclassified fell within the normal weight range according to their BF%. Finally, regarding the obesity group, 34% who were classified as having obesity according to the BMI were misclassified, since they were revealed to be only affected by overweight according to adiposity status. Conclusions: Despite the fact that the BMI seems to be reliable in determining body weight status in the normal weight range, over a third of the general population was misclassified, as the current BMI classification appears to inflate the prevalence of underweight, overweight, and obesity among the general population. Accordingly, this may warrant consideration of revising the National Guidelines in Italy related to weight status classification. Healthcare practitioners should be advised not to rely solely on the BMI, and should integrate its use with adiposity measures (i.e., BF%) or alternative surrogate indicators (i.e., waist-based) in routine evaluations, especially in those with a BMI below or above 18.5 kg/m² or 25 kg/m². Full article

Background/Objectives: The maternal mortality ratio is one of the global health indicators, and cardiopathies are the leading indirect causes of maternal deaths. Proper management of pregnant women with heart disease is crucial, as the severity of these conditions can lead to complications during the perinatal period. This study aimed to evaluate the rate of severe maternal morbidity and associated factors in pregnant women with heart disease. Methods: A retrospective cohort study was conducted at a referral hospital in São Paulo from 2008 to 2017, including pregnant women with heart disease who underwent procedures in the obstetric center (n = 345). Sociodemographic, obstetric, and pre-existing conditions were analyzed, along with life-threatening conditions, near-miss events, and maternal deaths. Heart diseases were classified according to the World Health Organization (WHO) guidelines, and health indicators were calculated using WHO-recommended formulas. The Chi-square test or Likelihood Ratio test (p < 0.05) was used to compare severe maternal morbidity among women with heart disease. Results: The mean age of participants was 29.1 ± 7.29 years; most were white (58.8%), had completed high school (37.9%), and were married (71.6%). The most frequent pre-existing conditions were hypertension (9.6%) and diabetes mellitus (9.3%). The mean gestational age at admission/delivery was 37 weeks. According to the WHO classification, most women were classified as “II/III” (31.6%). Life-threatening conditions included hemorrhagic complications (13.9%), hypertensive complications (5.8%), clinical complications (19.7%), and severe management conditions (31.6%). Near-miss events occurred in 6.4% of patients, with clinical criteria in 2.9%, laboratory criteria in 4.3%, and management criteria in 3.5%. The cesarean section rate was 51%. Patients classified as WHO III and IV presented more severe management conditions (p < 0.0001), and those in WHO IV had a higher occurrence of near-miss events (p = 0.0001). Maternal mortality was 0.9% (n = 3). Conclusions: The incidence of severe maternal morbidity was 25 cases (22 near-miss events + 3 maternal deaths), equivalent to 2.86 per 1000 live births, and was significantly associated with WHO classifications III and IV. Full article

Gliomas are incurable, heterogeneous brain tumors, with rare forms often constituting diagnostic and treatment challenges. Molecular diagnostics, mainly implemented through the World Health Organization (WHO) 2021 guidelines, have refined the classification, but highlight difficulties in diagnosing rare gliomas remain. This case series analyzes four patients with rare gliomas treated at the University Hospital, Ulm, between 2002 and 2024. Patients were selected based on unique histopathological features and long-term clinical follow-up. Clinical records, imaging, and histological data were reviewed. Molecular diagnostics followed WHO 2021 guidelines. Quality of life was assessed using standardized tools including the EQ-5D-5L, EQ VAS, the Distress Thermometer, and the Montreal Cognitive Assessment (MoCA). In the first case, a 51-year-old male’s diagnosis evolved from pleomorphic xanthoastrocytoma to a high-grade glioma with pleomorphic and pseudopapillary features, later identified as a neuroepithelial tumor with a PATZ1 fusion over 12 years. Despite multiple recurrences, extensive surgical interventions led to excellent outcomes. The second case involved a young female with long-term survival of astroblastoma, demonstrating significant improvements in both longevity and quality of life through personalized care. The third case involved a patient with oligodendroglioma, later transforming into glioblastoma, emphasizing the importance of continuous diagnostic reevaluation and adaptive treatment strategies, contributing to prolonged survival and quality of life improvements. Remarkably, the patient has achieved over 20 years of survival, including 10 years of being both therapy- and progression-free. The fourth case presents a young woman with neurofibromatosis type 1, initially misdiagnosed with glioblastoma based on histopathological findings. Subsequent molecular diagnostics revealed a subependymal giant cell astrocytoma-like astrocytoma, highlighting the critical role of early advanced diagnostic techniques. These cases underscore the importance of precise molecular diagnostics, individualized treatments, and ongoing diagnostic reevaluation to optimize outcomes. They also address the psychological impact of evolving diagnoses, stressing the need for comprehensive patient support. Even in complex cases, extensive surgical interventions can yield favorable results, reinforcing the value of adaptive, multidisciplinary strategies based on evolving tumor characteristics. Full article

Nowadays, antimicrobial resistance (AMR) is a growing global health threat, with carbapenem-resistant Enterobacteriaceae (CRE) posing particular concern due to limited treatment options. In fact, CRE have been classified as a critical priority by the World Health Organization (WHO). Carbapenem resistance results from complex mechanisms, often combining the production of hydrolytic enzymes such as β-lactamases with reduced membrane permeability and efflux system induction. The Ambler classification is an effective tool for differentiating the characteristics of serine-β-lactamases (SβLs) and metallo-β-lactamases (MβLs), including ESβLs (different from carbapenemases), KPC, NDM, VIM, IMP, AmpC (different from carbapenemases), and OXA-48. Recently approved inhibitor drugs, such as diazabicyclooctanones and boronic acid derivatives, only partially address this problem, not least because of their ineffectiveness against MβLs. However, compared with taniborbactam, xeruborbactam is the first bicyclic boronate in clinical development with a pan-β-lactamase inhibition spectrum, including the IMP subfamily. Recent studies explore strategies such as chemical optimization of β-lactamase inhibitor scaffolds, novel β-lactam/β-lactamase inhibitor combinations, and siderophore–antibiotic conjugates to enhance bacterial uptake. A deeper understanding of the mechanistic properties of the active sites enables rational drug design principles to be established for inhibitors targeting both SβLs and MβLs. This review aims to provide a comprehensive overview of current therapeutic strategies and future perspectives for the development of carbapenemase inhibitor drug candidates. Full article

Background/Objectives: This study evaluates intratumoral susceptibility signals (ITSS) as imaging markers for glioma grade prediction and their association with molecular and histopathologic features, in the context of the fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5). Methods: We retrospectively analyzed patients with adult diffuse gliomas who underwent pretreatment magnetic resonance imaging. ITSS were semiquantitatively graded by two radiologists: grade 0 (no signal), grade 1 (1–5), grade 2 (6–10), and grade 3 (≥11). Relative cerebral blood volume (rCBV) and tumor volume were also obtained. Histopathologic features included tumor grade, Ki-67, mitotic count, necrosis, microvascular proliferation, and molecular alterations (isocitrate dehydrogenase [IDH], 1p/19q, cyclin-dependent kinase inhibitors 2A and 2B [CDKN2A/B], and p53). Regression models predicted tumor grade (low: 1–2, high: 3–4) using ITSS, tumor volume, and rCBV. ROC curves and diagnostic performance metrics were analyzed. Results: 99 patients were included. ITSS grading correlated with rCBV, tumor volume, mitotic count, Ki-67, and tumor grade (p < 0.001). ITSS grades 0–1 were associated with oligodendrogliomas and astrocytomas (p < 0.001), IDH mutations (p < 0.001), and 1p/19q co-deletions (p = 0.01). ITSS grades 2–3 were linked to glioblastomas (p < 0.001), necrosis (p < 0.001), microvascular proliferation (p < 0.001), and CDKN2A/B homozygous deletions (p = 0.02). Models combining ITSS with rCBV and volume showed AUC of 0.94 and 0.96 (p < 0.001), outperforming univariate models. Conclusions: Semiquantitative ITSS grading correlates with key histopathologic and molecular glioma features. Combined with perfusion and volumetric parameters, ITSS enhance non-invasive glioma grading, in alignment with WHO CNS5. Full article

Background/Objectives: The purpose of this study was to determine the incidence of salivary gland tumors based on age, gender, histological type, and localization over an eleven-year period at the University Hospital of Split. Methods: The medical records of the Department of Otorhinolaryngology with Head and Neck Surgery and the Department of Maxillofacial Surgery at the University Hospital of Split regarding salivary gland tumors were searched from January 2012 to December 2022. The current fifth World Health Organization (WHO) Classification of Head and Neck Tumors and its criteria were considered during that process. Results: Out of 404 patients, 211 (52.20%) were female and 193 (47.77%) male. The mean age was 60. There were four pediatric patients. Six patients had a combination of two different histological types of salivary gland tumors present simultaneously at the exact localization. Therefore, there were 410 histological types in total, 214 related to females and 196 to males. A total of 361 (88.05%) benign and 49 (11.95%) malignant primary salivary gland tumors were detected. The parotid gland was the predominant location (N = 361, 87.8%). There were no cases affecting the sublingual gland. Pleomorphic adenoma was the most common benign histological type (N = 169, 41.2%). The most common malignant histological types were adenoid cystic carcinoma (N = 9, 2.2%) and mucoepidermoid carcinoma (N = 9, 2.2%). The average incidences of salivary gland tumors in the 11 years for the four Dalmatian counties and the Republic of Croatia were 4.45/100,000 and 0.9/100,000, respectively. Conclusions: The results of this study, primarily the ones concerning histological types and localization, do not deviate from general knowledge about salivary gland tumors. Simultaneous and ipsilateral occurrence of different histological types is a rare and extremely valuable finding. The average incidence for Dalmatian counties and the Republic of Croatia is within the range of the International Agency for Research on Cancer estimates. Full article

Background: Early detection of severe dengue (SD) is crucial in preventing life-threatening complications. Despite its importance, comprehensive knowledge about these early indicators is still limited. This study aimed to identify predictors of SD in a hyperendemic region of Colombia. Methods: A cross-sectional analysis was conducted using data from 2018 to 2022, encompassing 233 patients. By utilizing the 2009 World Health Organization dengue classifications, cases were differentiated between severe dengue (SD) and non-severe dengue (non-SD). Among these, 47 were confirmed as SD. Associations between clinical, demographic, and laboratory data and disease severity were examined using Fisher’s exact tests or the Mann–Whitney U test (p < 0.05). Profiles for SD and non-SD cases were established through multiple correspondence analysis, and a logistic regression-based predictive model was validated using training and test sets. The model’s performance was evaluated using the area under the receiver operating characteristic curve (AUC-ROC), accuracy, sensitivity, F1-score, and precision. Results: Differences in place of residence, comorbidities, type of infection, and signs and symptoms were observed between the severe dengue (SD) and non-severe dengue (non-SD) groups. Median levels of platelets, white blood cells (WBC), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were found to be higher in the SD group compared to the non-SD group. Neutrophils, leukocytes, platelets, AST, and primary infection were significant predictors of SD. The model demonstrated an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI, 0.85–0.96). Conclusions: The developed predictive model provides significant assistance to clinicians in assessing SD risk and optimizing triage, which is particularly crucial during dengue outbreaks. Full article

The Life Impact Burn Recovery Evaluation (LIBRE) Profile was developed to assess long-term social participation outcomes for adult burn survivors. Traditional clinical burn recovery outcomes focus on early physical complications and psychosocial issues, but there is a growing need for quantitative measures of long-term recovery that assess experiences deemed relevant to burn survivors. The LIBRE Profile, co-produced with input from burn survivors and clinicians and grounded in the World Health Organization’s International Classification of Functioning, Disability and Health (WHO-ICF) conceptual framework, addresses the measurement gap by focusing on six domains of social participation: social interactions, social activities, family and friends, work and employment, romantic relationships, and sexual relationships. The LIBRE Profile uses Item Response Theory (IRT) and computer adaptive tests (CAT) to minimize respondent burden while maintaining accuracy. Psychometric evaluations have validated the LIBRE Profile as a reliable and clinically useful tool that can help clinicians and burn survivors monitor recovery and inform personalized care. Future work includes LIBRE Profile development for pediatric populations, further international language translations, and the development of an APP for broader personal and clinical use. This paper provides a comprehensive overview of the LIBRE Profile’s development, psychometric foundations, and future directions, advocating for its adoption in clinical practice and burn survivor communities. Full article

Background: Although several studies investigated the efficacy of long-term adjuvant temozolomide (TMZ) therapy in glioblastomas (GBs), no univocal data are currently available, and this topic remains controversial. The present study on our ongoing experience aims to assess whether the extended STUPP protocol confers prognostic benefits with acceptable safety. Methods: From 2004 to 2018, 81 patients with a new diagnosis of GB according to the World Health Organization (WHO) 2021 classification, treated with gross total resection (GTR) or subtotal resection (STR), were enrolled. Patients were divided into Group A (long-term TMZ; N = 40) and Group B (standard STUPP protocol; N = 41). Results: In the extended STUPP group, compared with the standard STUPP group, progression-free survival (PFS) and overall survival (OS) were significantly improved (PFS: 27.8 vs. 7.5 months, p = 0.00001; OS: 35.9 vs. 11.3 months, p = 0.0001). To mitigate a potential survival bias, we focused on those in Group B who completed the recommended six cycles. Patients in Group A demonstrated a prolonged OS compared to Group B (27 vs. 10 months, p < 0.001). Similar findings were observed in a focused analysis of patients who had achieved a minimum survival of 12 months (27 vs. 15 months, p < 0.001) or 18 months (34 vs. 24 months, p = 0.044). Conclusions: Our analysis demonstrates a PFS and OS advantage with extended STUPP and suggests that young patients without corpus callosum invasion, with methylguanine-DNA methyltransferase (MGMT) promoter methylation, and treated with GTR are the best candidates. No significant safety difference emerged between extended and standard TMZ treatment. Full article

Background/Objectives: The World Health Organization’s (WHO) classification of tumors contains around 80 entities of soft tissue sarcomas (STSs). Currently, surgery is the standard treatment for patients with localized STS, but the adequacy of resection margins in soft tissue sarcomas (STSs) remains a topic of intense discussion. Methods: This single-center study retrospectively reviewed 203 patients with primary high-grade soft tissue sarcoma, including a follow-up period of at least 24 months. Patients with prior resection, secondary STS, metastasis at presentation, or those who required amputational surgery were excluded from the study. Patients were categorized based on their margin thickness: positive (n = 13, 6.4%), 0–1 mm (n = 67, 33.0%), 1–5 mm (n = 70, 34.5%), and >5 mm (n = 27, 13.3%). Results: A total of 64 out of 203 (31.5%) patients developed a local recurrence. The estimated 5-year local-recurrence-free survival (LRFS) was 11.5% (CI 4–25%) for positive margins, 58% (CI 51–64%) for margins 0–1 mm, 76% (CI 70–81%) for margins > 1–5 mm, and 93% (CI 88–98%) for margins > 5 mm. No local recurrences occurred in patients with margins > 5 mm and adjuvant radiotherapy. Margin status significantly influenced the development of distant metastasis and overall survival. Adjuvant radiotherapy improved both local control and overall survival. Conclusions: To minimize the risk of local recurrence (LR), a resection margin greater than 5 mm should be attained. When adjuvant radiotherapy is applied, the likelihood of LR decreases even more. In scenarios where preserving critical structures is essential, a resection margin of less than 5 mm can be acceptable for ensuring local control. Full article

Smart textiles are an evolving field, but challenges in durability, washing, interfacing, and sustainability persist. Widespread adoption requires robust, lightweight, fully integrated fiber-based conductors. This paper proposes using ultralong carbon nanotube (UCNT) yarns with a width-to-length ratio of several orders of magnitude larger than typical carbon nanotube fibers. These yarns enable the manufacturing of stable, workable structures, composed of a network of twisted fibers (tows), which are suitable for fabric integration. Our research includes the creation of textile prototype demonstrators integrated with coated and non-coated UCNT yarns, tested under military-grade standards for both mechanical durability and electric functionality. The demonstrators were evaluated for their electrical and mechanical properties under washability, abrasion, and weathering. Notably, polymer-coated UCNT yarns demonstrated improved mechanical durability and electrical performance, showing promising results. However, washing tests revealed the presence of UCNT nanofibers in the residue, raising concerns due to their classification as hazards by the World Health Organization. This paper examines the sources of fiber release and discusses necessary improvements to coating formulations and testing protocols to mitigate fiber loss and enhance their practical viability. These findings underscore both the potential and limitations of UCNT yarns in military textile applications. Full article

Background: The discovery of antibiotics revolutionized healthcare by significantly reducing morbidity and mortality. However, excessive and inappropriate use has led to a global surge in antimicrobial resistance, particularly in low- and middle-income countries. This study aimed to evaluate antibiotic use patterns among inpatients at Jimma Medical Center (JMC) in Southwest Ethiopia. Methods: A longitudinal observational study was conducted in February and March 2019 at JMC, focusing on patients admitted for over 24 h who received antibiotics. Data on patient demographics, clinical indications, and antibiotics prescribed were systematically collected. Antibiotic consumption rates were measured as days of therapy (DOTs) per 100 patient-days, and utilization was classified according to the World Health Organization (WHO) AWaRe (Access, Watch, and Reserve) framework. Results: A total of 384 inpatients were included, with a male predominance (53.9%) and a median age of 24 years (IQR: 5–37). In total, 634 antibiotic regimens were prescribed. According to the WHO AWaRe classification, 48.3% (306/634) were “Access” and 51.7% (328/634) were “Watch” antibiotics. Patients were treated with antibiotics for a median duration of 4 days (IQR: 2–7), leading to a total of 2880 days of antibiotic therapy. Ceftriaxone was the most commonly prescribed antibiotic, with a usage rate of 44.65 DOTs per 100 patient-days. Substantial variability was observed in empirical antibiotic regimens among treating physicians and across wards. Culture and antibiotic susceptibility testing (AST) were performed for only 4.2% of patients, and none of the treatments were modified based on susceptibility data. Conclusions: The study highlights critical issues in antibiotic prescribing at JMC, including over-reliance on “Watch” antibiotics, predominantly ceftriaxone, limited use of AST results, and deviations from standard treatment guidelines. Addressing these challenges requires implementing antimicrobial stewardship programs, developing evidence-based local treatment guidelines, and strengthening and encouraging the use of microbiology services to improve rational antibiotic use. Full article

Background/Objectives: Primary cutaneous B-cell lymphomas (PCBCL) are a rare and heterogeneous group of non-Hodgkin lymphomas that are confined to the skin at diagnosis and exhibit a tendency for cutaneous recurrence. The 5th edition of the World Health Organization and the 2022 International Consensus Classification recognize three main subtypes: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma/lymphoproliferative disorder (PCMZL/LPD), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL,LT). These subtypes differ in clinical behavior, histopathologic features, immunophenotype, and molecular alterations. Diagnosis and management remain challenging for clinicians. This review aims to provide a comprehensive overview of the defining features and current treatment strategies for PCBCL. Methods: This narrative review synthesizes current literature on the clinical, morphologic, immunohistochemical, and molecular characteristics of PCBCL. It also evaluates the diagnostic utility of immunohistochemistry, gene expression profiling, and molecular assays, particularly in distinguishing primary cutaneous disease from secondary cutaneous involvement by systemic lymphomas. Results: PCFCL arises from germinal center B-cells and must be differentiated from nodal follicular lymphoma. PCMZL/LPD is derived from post-germinal center B-cells and is often linked to chronic antigenic stimulation. Both PCFCL and PCMZL/LPD are indolent and associated with favorable outcomes. By contrast, PCDLBCL,LT is an aggressive lymphoma characterized by genetic alterations activating the NF-κB pathway, commonly including mutations to MYD88 and CD79B. Treatment strategies vary by subtype, ranging from localized therapies for indolent lymphomas to systemic chemoimmunotherapy for aggressive PCBCL. Emerging therapies, such as Bruton tyrosine kinase inhibitors and immunoregulatory agents, are being investigated for relapsed/refractory disease. Conclusions: PCBCL encompass distinct clinicopathologic entities with subtype-specific diagnostic and therapeutic considerations. While current management is guided by clinical behavior, significant knowledge gaps remain regarding the molecular mechanisms underlying skin tropism, immune evasion, and disease progression. Future research could focus on improving molecular characterization and developing personalized and immune-based therapies to enhance outcomes. This review consolidates current knowledge and highlights innovations aimed at advancing the diagnosis and treatment of PCBCL in clinical practice. Full article

Internet Gaming Disorder (IGD) has been recognized by the World Health Organization (WHO) in the International Classification of Diseases (ICD-11) and as an emerging condition in the DSM-5. IGD is increasingly prevalent, with various negative effects on individuals’ development and adaptation. To address this issue, different therapeutic interventions, like CBT, virtual reality, mindfulness, or family therapy, have been explored. This systematic review aimed to answer the following research question: What is the effectiveness of therapeutic interventions in reducing IGD symptoms in adolescents and young adults diagnosed with this disorder? Following PRISMA guidelines, 22 studies published between 2014 and 2025 were included. Results show that cognitive behavioral therapy (CBT) is the most effective intervention, significantly reducing IGD severity, anxiety, and depression. Combining CBT with physical exercise or mindfulness further enhanced outcomes. Other promising approaches include virtual reality (VR), transcranial direct current stimulation (tDCS), and family-based interventions. Additionally, treatments involving mindfulness and animal-assisted therapy showed potential in improving emotional regulation and interpersonal relationships. However, further research is needed to evaluate long-term efficacy and explore emerging therapies. Full article

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced non-small cell lung cancer (NSCLC). Emerging evidence suggests a potential association between elevated body mass index (BMI) and enhanced ICI efficacy, yet this relationship remains inconclusive and warrants further investigation. This study aims to evaluate the impact of BMI on treatment efficacy and survival outcomes in advanced NSCLC patients treated with first-line ICI therapy. Methods: A retrospective study was conducted at a multi-center registry to evaluate the impact of baseline BMI on overall survival (OS) and progression-free survival (PFS) in patients with stage IV NSCLC who received first-line ICI therapies. Treatment regimens included pembrolizumab or the combination of ipilimumab and nivolumab, administered either as monotherapy or in combination with chemotherapy, at the oncology department between January 2018 and December 2023. BMI was categorized according to the World Health Organization (WHO) classification, and OS and PFS were evaluated using Kaplan–Meier survival analysis and the Cox proportional hazards regression model. Results: Among 346 patients, 12.72% were underweight, 45.38% normal weight, 29.19% overweight, and 12.72% obese. Overweight and obese patients were more likely to receive pembrolizumab (p = 0.039) and less likely to undergo chemotherapy (p = 0.012). No significant differences in median overall survival (OS, log-rank: p = 0.155) or progression-free survival (PFS, log-rank: p = 0.370) were observed across BMI categories. However, differences emerged upon further analysis of PD-L1 levels (OS, log-rank: p = 0.029; PFS, log-rank: p = 0.044), additional chemotherapy (OS, log-rank: p = 0.009; PFS, log-rank: p = 0.021), type of immune checkpoint inhibitor (OS, log-rank: p < 0.001; PFS, log-rank: p < 0.001), and histologic diagnosis (OS, log-rank: p = 0.011; PFS, log-rank: p = 0.003). Conclusions: BMI was not an independent predictor of survival outcomes in advanced NSCLC treated with ICI. Incorporating BMI with other patient-specific factors into personalized immunotherapy strategies highlights the importance of tailored approaches to improve patient care and clinical outcomes. Full article