Establishing Standardization Guidelines For Finite-Element Optomechanical Simulations of Refractive Laser Surgeries: An Application to Photorefractive Keratectomy.

Purpose: Computational models can help clinicians plan surgeries by accounting for factors such as mechanical imbalances or testing different surgical techniques beforehand. Different levels of modeling complexity are found in the literature, and it is still not clear what aspects should be included to obtain accurate results in finite-element (FE) corneal models. This work presents a methodology to narrow down minimal requirements of modeling features to report clinical data for a refractive intervention such as PRK. Methods: A pipeline to create FE models of a refractive surgery is presented: It tests different geometries, boundary conditions, loading, and mesh size on the optomechanical simulation output. The mechanical model for the corneal tissue accounts for the collagen fiber distribution in human corneas. Both mechanical and optical outcome are analyzed for the different models. Finally, the methodology is applied to five patient-specific models to ensure accuracy. Results: To simulate the postsurgical corneal optomechanics, our results suggest that the most precise outcome is obtained with patient-specific models with a 100 µm mesh size, sliding boundary condition at the limbus, and intraocular pressure enforced as a distributed load. Conclusions: A methodology for laser surgery simulation has been developed that is able to reproduce the optical target of the laser intervention while also analyzing the mechanical outcome. Translational Relevance: The lack of standardization in modeling refractive interventions leads to different simulation strategies, making difficult to compare them against other publications. This work establishes the standardization guidelines to be followed when performing optomechanical simulations of refractive interventions.

Mapping the concept of health care integration: A lexicographic analysis of scientific literature.

BACKGROUND: Systems fragmentation is a major challenge for an efficient organization, integration being a potential solution also proposed in health care field, including pharmacy as a player. However, the use of different terms and definitions in the literature hinders the comparison of different integration initiatives. OBJECTIVE: To identify and map the terms used in scientific literature regarding integration in health care and to characterize each emerging topic. METHODS: A lexicographic analysis of the integration of healthcare systems literature indexed in PubMed was conducted. Ten different systematic searches, four using only Medical Subject Headings (MeSH) and six using text words, were conducted in March 2023. Journal scattering was analyzed following Bradford's distribution using the Leimkuhler model. An overall text corpus was created with titles and abstracts of all the records retrieved. The corpus was lemmatized, and the most used bigrams were tokenized as single strings. To perform a topic modeling, the lemmatized corpus text was analyzed using IRaMuTeQ, producing descending hierarchic classification and a correspondence analysis. The 50 words with higher chi-square statistics in each class were considered as representative of the class. RESULTS: A total of 42,479 articles published from 1943 to 2023 in 4469 different journals were retrieved. The MeSH "Delivery of Health Care, Integrated", created in the 1996 MeSH update, was the most productive retrieving 33.7 % of the total articles but also retrieving 22.6 % of articles not retrieved in any other search. The text word "Integration" appeared in 15,357 (36.2 %) records. The lexicographic analysis resulted in 7 classes, named as: Evidence and implementation, Quantitative research, Professional education, Qualitative research, Governance and leadership, Clinical research, and Financial resources. Association between the classes and the searches or the text-words used ranged from moderate to weak demonstrating the lack of a standard pattern of use of terms in literature regarding healthcare integration. CONCLUSIONS: The term "integration" and the MeSH "Delivery of Health Care, Integrated" are the most used to represent the concept of integration in healthcare and should be the preferred terms in the literature.

Improving early detection of keratoconus by Non Contact Tonometry. A computational study and new biomarkers proposal.

Keratoconus is a progressive ocular disorder affecting the corneal tissue, leading to irregular astigmatism and decreased visual acuity. The architectural organization of corneal tissue is altered in keratoconus, however, data from ex vivo testing of biomechanical properties of keratoconic corneas are limited and it is unclear how their results relate to true mechanical properties in vivo. This study explores the mechanical properties of keratoconic corneas through numerical simulations of non-contact tonometry (NCT) reproducing the clinical test of the Corvis ST device. Three sensitivity analyses were conducted to assess the impact of corneal material properties, size, and location of the pathological area on NCT results. Additionally, novel asymmetry-based indices were proposed to better characterize corneal deformations and improve the diagnosis of keratoconus. Our results show that the weakening of corneal material properties leads to increased deformation amplitude and altered biomechanical response. Furthermore, asymmetry indices offer valuable information for locating the pathological tissue. These findings suggest that adjusting the Corvis ST operation, such as a camera rotation, could enhance keratoconus detection and provide insights into the relative position of the affected area. Future research could explore the application of these indices in detecting early-stage keratoconus and assessing the fellow eye's risk for developing the pathology.

Evaluation of the mechanical stability of intraocular lenses using digital image correlation.

This study aimed to evaluate the mechanical stability of seven different intraocular lens (IOL) haptic designs by using digital image correlation to measure their mechanical biomarkers (axial displacement, tilt, and rotation) under quasi-static compression. The IOLs were compressed between two clamps from 11.00 up to 9.50 mm whilst a 3D deformation dataset was acquired every 0.04 mm. Results revealed that flexible and mixed IOL designs exhibited better mechanical response for smaller compression diameters compared to stiff designs. Conversely, stiff designs performed better for larger compression diameters. These findings may aid in the selection and development of more mechanically stable IOL designs.

Autoimmune Diabetes From Childhood to Adulthood: The Role of Pancreatic Autoantibodies and HLA-DRB1 Genotype.

CONTEXT: Autoimmune diabetes can develop at any age, but unlike early-onset diabetes, adult onset is less well documented. We aimed to compare, over a wide age range, the most reliable predictive biomarkers for this pathology: pancreatic-autoantibodies and HLA-DRB1 genotype. METHODS: A retrospective study of 802 patients with diabetes (aged 11 months to 66 years) was conducted. Pancreatic autoantibodies at diagnosis: insulin autoantibodies (IAA), glutamate decarboxylase autoantibodies (GADA), islet tyrosine phosphatase 2 autoantibodies (IA2A), and zinc transporter-8 autoantibodies (ZnT8A) and HLA-DRB1 genotype were analyzed. RESULTS: Compared with early-onset patients, adults had a lower frequency of multiple autoantibodies, with GADA being the most common. At early onset, IAA was the most frequent in those younger than 6 years and correlated inversely with age; GADA and ZnT8A correlated directly and IA2A remained stable.The absence of HLA-DRB1 risk genotype was associated with higher age at diabetes onset (27.5 years; interquartile range [IQR], 14.3-35.7), whereas the high-risk HLA-DR3/DR4 was significantly more common at lower age (11.9 years; IQR, 7.1-21.6). ZnT8A was associated with DR4/non-DR3 (odds ratio [OR], 1.91; 95% CI, 1.15-3.17), GADA with DR3/non-DR4 (OR, 2.97; 95% CI, 1.55-5.71), and IA2A with DR4/non-DR3 and DR3/DR4 (OR, 3.89; 95% CI, 2.28-6.64, and OR, 3.08; 95% CI, 1.83-5.18, respectively). No association of IAA with HLA-DRB1 was found. CONCLUSION: Autoimmunity and HLA-DRB1 genotype are age-dependent biomarkers. Adult-onset autoimmune diabetes is associated with lower genetic risk and lower immune response to pancreatic islet cells compared with early-onset diabetes.

Quantification of scleral changes during dynamic accommodation.

The mechanics of accommodation is a complex process that involves multiple intraocular ocular structures. Recent studies suggest that there is deformation of the sclera during accommodation that may also play a role in accommodation, influencing ciliary muscle contraction and contributing to the accommodative response. However, the type and magnitude of the deformations measured varies significantly across studies. We present high-resolution synchronous OCT measurements of the anterior sclera contour and thickness and lens thickness acquired in real-time during accommodative responses to 4D step stimuli. The lens thickness was used as an assessment of objective accommodation. No changes in nasal and temporal anterior scleral contour and scleral thickness were found during accommodation within the precision of our measurements. Our results demonstrate that there are no significant scleral deformations during accommodation.

Community pharmacy and primary health care - Types of integration and their applicability: A narrative review.

BACKGROUND: There is an urgent need for health care systems to be more efficient and efficacious. An approach to integrate public and private provider organizations such as community pharmacies and public primary health care (PHC) merits consideration. The objective of this review was to identify the types of integration in health care settings and discuss their applicability to the potential integration of community pharmacy and PHC. METHODS: A narrative review using Medline, Scopus and SciELO databases was performed in which terms related to health were combined with terms related to integration. Levels and Types of integration: 14 types of integration were identified (two in breadth, seven as enablers and five in system levels). A model was created which classifies and assigns the types of integration to the different levels of the health system and to the breadth, intensity, and enablers of the integration process. Due to the nature of community pharmacy and PHC system, a horizontal integration at the micro level, supported by meso and macro levels policy, is suggested. The different elements of intensity and enablers can significantly influence the process. CONCLUSION: The application of principles, concepts and types of integration suggest that it might be feasible and practical to integrate community pharmacies and PHC. However, the conflictive historical context would need to be overcome with appropriate policy and incentives.

A detailed methodology to model the Non Contact Tonometry: a Fluid Structure Interaction study.

Understanding the corneal mechanical properties has great importance in the study of corneal pathologies and the prediction of refractive surgery outcomes. Non-Contact Tonometry (NCT) is a non-invasive diagnostic tool intended to characterize the corneal tissue response in vivo by applying a defined air-pulse. The biomarkers inferred from this test can only be considered as indicators of the global biomechanical behaviour rather than the intrinsic biomechanical properties of the corneal tissue. A possibility to isolate the mechanical response of the corneal tissue is the use of an inverse finite element method, which is based on accurate and reliable modelling. Since a detailed methodology is still missing in the literature, this paper aims to construct a high-fidelity finite-element model of an idealized 3D eye for in silico NCT. A fluid-structure interaction (FSI) simulation is developed to virtually apply a defined air-pulse to a 3D idealized eye model comprising cornea, limbus, sclera, lens and humors. Then, a sensitivity analysis is performed to examine the influence of the intraocular pressure (IOP) and the structural material parameters on three biomarkers associated with corneal deformation. The analysis reveals the requirements for the in silico study linked to the correct reproduction of three main aspects: the air pressure over the cornea, the biomechanical properties of the tissues, and the IOP. The adoption of an FSI simulation is crucial to capture the correct air pressure profile over the cornea as a consequence of the air-jet. Regarding the parts of the eye, an anisotropic material should be used for the cornea. An important component is the sclera: the stiffer the sclera, the lower the corneal deformation due to the air-puff. Finally, the fluid-like behavior of the humors should be considered in order to account for the correct variation of the IOP during the test which will, otherwise, remain constant. The development of a strong FSI tool amenable to model coupled structures and fluids provides the basis to find the biomechanical properties of the corneal tissue in vivo.

Automated segmentation of the ciliary muscle in OCT images using fully convolutional networks.

Quantifying shape changes in the ciliary muscle during accommodation is essential in understanding the potential role of the ciliary muscle in presbyopia. The ciliary muscle can be imaged in-vivo using OCT but quantifying the ciliary muscle shape from these images has been challenging both due to the low contrast of the images at the apex of the ciliary muscle and the tedious work of segmenting the ciliary muscle shape. We present an automatic-segmentation tool for OCT images of the ciliary muscle using fully convolutional networks. A study using a dataset of 1,039 images shows that the trained fully convolutional network can successfully segment ciliary muscle images and quantify ciliary muscle thickness changes during accommodation. The study also shows that EfficientNet outperforms other current backbones of the literature.

Integration of community pharmacy in primary health care: The challenge.

Community pharmacies and pharmacists predominantly operate in a retail environment independently of other health care providers, and they are not often viewed as an integral member of the healthcare team. Thus, they remain overlooked or excluded during integration processes of health care systems. At the same time, there are calls by the profession at national and international levels for community pharmacy to be integrated within primary care systems. The COVID-19 pandemic appears to have further stimulated this desire. When pressing for integration, various terms, such as integration, integrated care, or interprofessional collaboration, are used in an interchangeable manner leading to lack of clarity, ambiguity and confusion for health care policy makers, planners, and other healthcare professionals. The literature was reviewed to identify critical components for community pharmacy to consider for integration. From the five selected articles describing integration of community pharmacies, four different constructs were identified: consensus, connectivity, communication and trust. The integration of community pharmacy into the health system may translate into better access for patients to primary care services, contribute to cost effectiveness, and promulgate the sustainability of the system. However significant political, economic, social, and practice change would be required by all stakeholders. Further research is needed to underpin a consensus for a definition, the type of integration, and the model optimally suited to integrate community pharmacy into primary care. These models, specific and adaptable to each national health care system and political environment, would need to be consensus-based by principal stakeholders to overcome a variety of barriers, including government resistance. Mere calls or demands by the pharmaceutical profession, although laudable, will not be sufficient to overcome the historical, cultural, and economic challenges.

Self-adhesive hydrogel meshes reduce tissue incorporation and mechanical behavior versus microgrips self-fixation: a preclinical study.

PURPOSE: Atraumatic mesh fixation for abdominal hernia repair has been developed to avoid the disadvantages of classical fixation with sutures, which is considered a cause of chronic pain and discomfort. This study was designed to analyze, in the short and medium term, the biological and mechanical behavior of two self-fixing meshes compared to that of a polypropylene (PP) mesh fixed with a cyanoacrylate (CA) tissue adhesive. METHODS: Partial abdominal wall defects (6 × 4 cm) were created in New Zealand rabbits (n = 36) and repaired using a self-adhesive hydrogel mesh (Adhesix™), a self-gripping mesh (ProGrip™) or a PP mesh fixed with CA (Surgipro™ CA). After 14 and 90 days, the host tissue incorporation, macrophage response and biomechanical strength were examined. RESULTS: At 14 and 90 days, the ProGrip and Surgipro CA meshes showed good host tissue incorporation; however, the Adhesix implants presented poor integration, seroma formation and a higher degree of shrinkage. The Adhesix hydrogel was completely reabsorbed at 14 days, whereas ProGrip microhooks were observed at all study times. The macrophage response was higher in the ProGrip and Surgipro CA groups at 14 and 90 days, respectively, and decreased over time. At 90 days, the ProGrip implants showed the highest tensile strength values and the Adhesix implants showed the highest failure stretch. CONCLUSION: Meshes with mechanical microgrip self-fixation (ProGrip) show better biological and mechanical behavior than those with adhesive hydrogel (Adhesix) in a preclinical model of abdominal hernia repair in rabbits.

A validated finite element model to reproduce Helmholtz's theory of accommodation: a powerful tool to investigate presbyopia.

PURPOSE: To reproduce human in vivo accommodation numerically. For that purpose, a finite element model specific for a 29-year-old subject was designed. Once the proposed numerical model was validated, the decrease in accommodative amplitude with age was simulated according to data available in the literature. METHODS: In contrast with previous studies, the non-accommodated eye condition was the reference configuration. Consequently, two aspects were specifically highlighted: contraction of the ciliary muscle, which was simulated by a continuum electro-mechanical model and incorporation of initial lens capsule stresses, which allowed the lens to become accommodated after releasing the resting zonular tension. RESULTS: The morphological changes and contraction of the ciliary muscle were calibrated accurately according to the experimental data from the literature. All dynamic optical and biometric lens measurements validated the model. With the proposed numerical model, presbyopia was successfully simulated. CONCLUSIONS: The most widespread theory of accommodation, proposed by Helmholtz, was simulated accurately. Assuming the same initial stresses in the lens capsule over time, stiffening of the lens nucleus is the main cause of presbyopia.

Muscular and Tendon Degeneration after Achilles Rupture: New Insights into Future Repair Strategies.

Achilles tendon rupture is a frequent injury with an increasing incidence. After clinical surgical repair, aimed at suturing the tendon stumps back into their original position, the repaired Achilles tendon is often plastically deformed and mechanically less strong than the pre-injured tissue, with muscle fatty degeneration contributing to function loss. Despite clinical outcomes, pre-clinical research has mainly focused on tendon structural repair, with a lack of knowledge regarding injury progression from tendon to muscle and its consequences on muscle degenerative/regenerative processes and function. Here, we characterize the morphological changes in the tendon, the myotendinous junction and muscle belly in a mouse model of Achilles tendon complete rupture, finding cellular and fatty infiltration, fibrotic tissue accumulation, muscle stem cell decline and collagen fiber disorganization. We use novel imaging technologies to accurately relate structural alterations in tendon fibers to pathological changes, which further explain the loss of muscle mechanical function after tendon rupture. The treatment of tendon injuries remains a challenge for orthopedics. Thus, the main goal of this study is to bridge the gap between clinicians' knowledge and research to address the underlying pathophysiology of ruptured Achilles tendon and its consequences in the gastrocnemius. Such studies are necessary if current practices in regenerative medicine for Achilles tendon ruptures are to be improved.

Community pharmacist interventions to improve adherence to lipid lowering medication and their influence on clinical outcomes: A systematic review and meta-analysis.

INTRODUCTION: Non-adherence is a major problem among patients with chronic diseases. Community pharmacists are ideally positioned to detect non-adherence and to provide patient-centred interventions. OBJECTIVE: To conduct a systematic review of the impact of community pharmacist interventions on patient adherence to lipid lowering medication (LLM) prescriptions and clinical outcomes. SEARCH METHOD: Five databases (MEDLINE, Cochrane Library, Science Direct, Scopus, and Web of Knowledge) were searched systematically to identify relevant reports published by December 2019. Study quality was assessed with the Cochrane risk of bias (RoB 2.0) tool. SELECTION CRITERIA: Controlled trials in which community pharmacists conducted an intervention to improve patient adherence to LLM and clinical outcomes were evaluated. MAIN RESULTS: Five studies (2408 participants) were included in the qualitative analysis. Four studies (n = 2266) were pooled in the meta-analysis. Participants in the intervention group (IG) had better adherence than those in the control group (CG) [odds ratio (OR) = 1.67; 95% confidence interval (CI) 1.38-2.02; P < 0.001; I2 = 54%]. Better adherence rates were obtained when adherence was measured with validated questionnaires than when medication-possession ratio (MPR) measurements were used. Total cholesterol (TC) levels were not included in the meta-analysis due to data variability among the studies. CONCLUSIONS: Pharmacist-led intervention can improve LLM adherence, but its influence on clinical outcomes, including lipid level control, remains to be clarified.

The medication discrepancy detection service: A cost-effective multidisciplinary clinical approach.

OBJECTIVE: To estimate the effectiveness of a Medication Discrepancy Detection Service (MDDS), a collaborative service between the community pharmacy and Primary Care. DESIGN: Non-controlled before-and-after study. SETTING: Bidasoa Integrated Healthcare Organisation, Gipuzkoa, Spain. PARTICIPANTS: The service was provided by a multidisciplinary group of community pharmacists (CPs), general practitioners (GPs), and primary care pharmacists, to patients with discrepancies between their active medical charts and medicines that they were actually taking. OUTCOMES: The primary outcomes were the number of medicines, the type of discrepancy, and GPs' decisions. Secondary outcomes were time spent by CPs, emergency department (ED) visits, hospital admissions, and costs. RESULTS: The MDDS was provided to 143 patients, and GPs resolved discrepancies for 126 patients. CPs identified 259 discrepancies, among which the main one was patients not taking medicines listed on their active medical charts (66.7%, n=152). The main GPs' decision was to withdraw the treatment (54.8%, n=125), which meant that the number of medicines per patient was reduced by 0.92 (9.12±3.82 vs. 8.20±3.81; p<.0001). The number of ED visits and hospital admissions per patient were reduced by 0.10 (0.61±.13 vs 0.52±0.91; p=.405 and 0.17 (0.33±0.66 vs. 0.16±0.42; p=.007), respectively. The cost per patient was reduced by €444.9 (€1003.3±2165.3 vs. €558.4±1273.0; p=.018). CONCLUSION: The MDDS resulted in a reduction in the number of medicines per patients and number of hospital admissions, and the service was associated with affordable, cost-effective ratios.

Corneal Biomechanics After Intrastromal Ring Surgery: Optomechanical In Silico Assessment.

Purpose: To provide a biomechanical framework to better understand the postsurgical optomechanical behavior of the cornea after ring implantation. Methods: Calibrated in silico models were used to determine the corneal shape and stresses after ring implantation. After mechanical simulations, geometric ray-tracing was used to determine the change in spherical equivalent. The effect of the surgical procedure, circadian variation of intraocular pressure, or the biomechanical weakening introduced by keratoconus (KC) were evaluated for each intrastromal ring. Results: Models predicted the postsurgical optomechanical response of the cornea at a population level. The localized mechanical effect of the additional intrastromal volume introduced by the implants (size and diameter) drives the postsurgical corneal response. However, central corneal stresses did not increase more than 50%, and thus implants did not strengthen the cornea globally. Because of the biomechanical weakening introduced by laser pocketing, continuous implants in a pocket resulted in higher refractive corrections and in the relaxation of the anterior stroma, which could slow down KC progression. Implants can move within the stroma, acting as a dynamic pivot point that modifies corneal kinematics and flattens the corneal center. Changes in stromal mechanical properties did not impact on refraction for normal or pathological corneas. Conclusions: Implants do not stiffen the cornea but create a local bulkening effect that regularizes the corneal shape by modifying corneal kinematics without canceling corneal motion. Translational Relevance: In silico models can help to understand corneal biomechanics, to plan patient-specific interventions, or to create biomechanically driven nomograms.

Biomechanical Stability of Three Intraocular Lenses With Different Haptic Designs: In Silico and In Vivo Evaluation.

PURPOSE: To assess the biomechanical stability of three different marketed intraocular lenses (IOLs) with different haptic designs (four-loop IOL [Micro F FineVision model] and double C-loop IOL [POD F and POD FT models], all manufactured by PhysIOL), in silico (computer simulation) and in vivo (in the context of lens surgery). METHODS: An in silico simulation investigation was performed using finite element modeling (FEM) software to reproduce the compression test defined by the International Organization for Standardization and in vivo implantation in patients in the context of lens surgery was evaluated 1 day and 3 months postoperatively. IOL decentration and rotation were tested. In addition, the stress and strains were analyzed with the finite element method. RESULTS: In the in silico evaluation, the compression force for the POD F IOL was slightly lower than for the POD FT IOL and Micro F IOL for all compression diameters. The axial displacement was maximum for the POD FT IOL and the tilt, rotation, and lateral decentration were substantially lower than the acceptable tolerance limits established in ISO 11979-2. In the in vivo evaluation, a total of 45 eyes from 45 patients were selected, 15 eyes for each IOL model under assessment. Statistically significant differences were found between the Micro F and POD F IOLs for lateral decentration in x-direction (in absolute value) at 3 months postoperatively (P = .03). CONCLUSIONS: Although statistically significant differences have been found when comparing the displacement, tilt, and rotation between the different lenses, these differences cannot be considered clinically relevant, which would suggest that all three IOL models yield excellent stability in those terms. FEM appears to be a powerful tool for numerical studies of the biomechanical properties of IOLs. [J Refract Surg. 2020;36(9):617-624.].

Effect of health professional intervention on adherence to statin use according to the cause of patient non-adherence.

Background Non-adherence is a problem that particularly affects those with chronic diseases. Studying causes for not following the treatment is necessary to choose the best intervention to improve non-adherence. Objective Analyze how the intentionality of non-adherence modulates the effects of professional intervention in patients with hypercholesterolemia. Setting: Community pharmacies and primary care centres in Spain. Methods A 6-month randomized controlled trial was conducted in 46 community pharmacies and 50 primary care centres in Spain. Adherence to statin therapy was measured with the Morisky-Green-Levine test. Non-adherence was classified based on the intentionality. Results 746 Patients were recruited for the study (465 non-adherent and 281 adherent). Of those, 237 were randomly assigned to the intervention group and 228 to the non-intervention group. The 56.5% of non-adherent patients were classified as unintentional non-adherents and 43.5% as intentional non-adherents. More patients in the intervention group finished being adherent compared with the non-intervention group (+ 17.2% for intentional non-adherents and + 27.4% for unintentional non-adherence). The percentage of patients in the intervention group who completed the study as adherent was higher among those who previously had unintentional non-adherence (66.4%) compared to those with intentional non- adherence (55.3%) (p < 0.001). Conclusion Intervention provided to patients with unintentional non-adherence was more effective than intervention provided to patients with intentional non- adherence.

Negative autoimmunity in a Spanish pediatric cohort suspected of type 1 diabetes, could it be monogenic diabetes?

OBJECTIVE: Monogenic diabetes can be misdiagnosed as type 1 or type 2 diabetes in children. The right diagnosis is crucial for both therapeutic choice and prognosis and influences genetic counseling. The main objective of this study was to search for monogenic diabetes in Spanish pediatric patients suspected of type 1 diabetes with lack of autoimmunity at the onset of the disease. We also evaluated the extra value of ZnT8A in addition to the classical IAA, GADA and IA2A autoantibodies to improve the accuracy of type 1 diabetes diagnosis. METHODS: Four hundred Spanish pediatric patients with recent-onset diabetes (mean age 8.9 ± 3.9 years) were analyzed for IAA, GADA, IA2A and ZnT8A pancreatic-autoantibodies and HLA-DRB1 alleles. Patients without autoimmunity and those with only ZnT8A positive were screened for 12 monogenic diabetes genes by next generation sequencing. RESULTS: ZnT8A testing increased the number of autoantibody-positive patients from 373 (93.3%) to 377 (94.3%). An isolated positivity for ZnT8A allowed diagnosing autoimmune diabetes in 14.8% (4/27) of pediatric patients negative for the rest of the antibodies tested. At least 2 of the 23 patients with no detectable autoimmunity (8%) carried heterozygous pathogenic variants: one previously reported missense variant in the INS gene (p.Gly32Ser) and one novel frameshift variant (p.Val264fs) in the HNF1A gene. One variant of uncertain significance was also found. Carriers of pathogenic variants had HLA-DRB1 risk alleles for autoimmune diabetes and clinical characteristics compatible with type 1 diabetes except for the absence of autoimmunity. CONCLUSION: ZnT8A determination improves the diagnosis of autoimmune diabetes in pediatrics. At least 8% of pediatric patients suspected of type 1 diabetes and with undetectable autoimmunity have monogenic diabetes and can benefit from the correct diagnosis of the disease by genetic study.