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The paper aims to examine the differences and similarities between the Dutch Civil Code of 1838 and the Serbian Civil Code of 1844. Although the historical circumstances of the two countries, their legal culture and their legal systems at the time of codification were significantly different, the author points to some similarities between their private law codes. Based on that comparison he distinguishes a more general problem of early modern codifications in the 19th century, namely the issue of legal transfer's logic, causes and outcomes. Both in the cases of the Dutch and the Serbian codifications the predominant stereotype in literature are that they were more or less copies of the model codes (the French Code Civil of 1804 and the Austrian Civil Code of 1811, respectively). The author points out that only recently some diverse intonations started to appear on this matter, related to the two codifications. He stresses that in both cases legal borrowings were in many aspects inventive, innovative and influenced by a variety of other sources. The author based his conclusion on a comparative analysis of different legal identities present in the Dutch and Serbian codes. On that ground he revises the concept of mixed legal systems and suggests that mixture of legal identities should be more flexible, less demanding and open-ended notion.

The author analyzes characteristics, importance and impact of the celebrated book Rhetoric from 1933, written by a famous Serbian lawyer and comedy writer Branislav Nusic. The a. points to shortage of literature about rhetoric among the Serbs in Hungary, and afterwards in Serbia, pointing that the most important book about rhetoric in XIX century was written not before 1844, also by a comedy writer, lawyer and one of the first law professors Jovan Sterija Popovic (but it was saved as a manuscript, which was published after 150 years in 1995). He also points to the position of rhetoric and of the literature about rhetoric in the world in the last centuries. He delineates route from the time when rhetoric entered into a crisis due to its formal and infertile approach up to appearance of the 'new rhetoric' in a wider meaning (differing it from Perelman's 'new rhetoric' in the strict sense), namely until appearance of the modern 'public speaking' approach and impact of Dale Carnegie. The a. finds many examples where Nusic's Rhetoric reflects his commitment to classical rhetoric, but also recognizes important steps toward its modernization. His attempt to update classical rhetoric was performed cautiously and with a proper measure. Therefore the a. is of opinion that it was Nusic's most important advantage, virtue and contribution. The flow of time has shown that it was his specific contribution to the identity of this discipline among the Serbs, as many generations were educated on his book, until our times. It is due to excellent concept and harmonious compound of classical rhetoric and elements of rhetoric from the first half of XX century. The a. compares Nusic with a modern American scholar Edward Corbett who claimed that classical rhetoric is still useful and effective - perhaps more useful and effective than the various courses of study that replaced it. Finally the a. points to dangers of unrefined public speaking trends. He insists that, upon Nusic's identity trace, rhetoric should be based still our times upon proper combination of classical rhetoric values and experiences of the new, public speaking, applied rhetoric.

The author analyses types of religious education in European and Serbian state-run schools searching for an innovative approach to existing classifications. He suggests four criteria to differ and categorize types of religious education in public schools, claiming that the actual taxonomy is often insufficient, inconsistent or perplexed (having usually been based upon one or two elements). He proposes categorization which encompasses point of view and interests of tax payers, of the politics, of the pupils and of the religious teachers. More criteria could lead to a better assessment of particular system of religious education. He also suggests that, apart from usual categorization in confessional and non-confessional religious education, it would be useful to introduce categories like 'mostly confessional' and 'mostly non-confessional', as clear-cut models are very rare. In addition to this he offers arguments why 'cognitive' type of religious education would be more proper label instead of 'non-confessional'. Further on the author examines controversies, disputes and manner of reintroduction of religious instruction in Serbian legislation after the fall of the communist regime in 2000 and presents the current situation, including very recent changes considering curricula. He points to some very distinctive features of religious education model in Serbia which could be of interest in comparative perspective, particularly in the time when many states in Europe tend to improve their religious education system. Finally, he points to importance of religious education in building religious identity of young generations in post-communist countries, and differs two types of religious identity - perceptive (intuitive) and cognitive (rational). He concludes that 'educating into religion' has to exist for some time in post-communist countries due to historical circumstances (within more or less confessional model). Additionally, he finds that it should be only gradually transformed into 'educating about religion' and 'education from religion' pattern, fostering cognitive religious identity to strengthen parallel with the perceptive one.

The author examines different issues considering legal and social standing of mercenaries, mostly being focused upon the fourth court speech (On the Estate of Nicostratus) of the Athenian speech-writer Isaeus, teacher of Demosthenes. On the one hand, he reveals a number of neglected data about mercenaries in terms of their legal activities in and out of their native polis. On the other hand, based on those findings and on other sources, the author studies the issue of Athenian civic identity in the case of mercenaries who spent years or decades out of their city-state without participating in the political life of the polis. In that context he examines the question of whether a mercenary was regarded as 'politikos' or 'idiotes'. As civic identity was mostly based on the citizenship, the author claims that mercenaries enjoyed a kind of sub-identity or 'frozen civic identity'.

Background/Aim. Phacoemulsification is a modern surgical technique for cataract operations. Through minimal corneal wound (2.2-2.7 mm) lens nucleus is emulsificated and arteficial lens is implanted in capsular bag. Complications during operations are possible, and can vary from minor to very serious one, with consecutive visual loss. One of possible complications is rupture of posterior lens capsule, which could happen in any stage of operation. The aim of this study was to evaluate results of monoblock arteficial lens implantation in sulcus on the remains of anterior capsule and capsulorhexis after posterior capsule rupture during phacoemulsification. Methods. This prospective, non-comparative study included 19 patients with rupture of posterior capsule as a result of cataract operation with phacoemulsification method. Average monitoring time was 14 months (1-18). We analysed best corrected visual acuity, intraocular pressure, fundus findings, and implanted lens position with wawelight allegro oculizer (Scheimpflug camera). Results. Preoperative visual acuity was from L+P+ to 0.5. On first postoperative day visual acuity 0.02-0.08 was noted in 8 patients, from 0.1-0.4 also in 8 patients and 0.5 and more in 3 patients. After 12 months from the operation 15 patients had visual acuity better than 0.5. Among early complications corneal edema was noted in 6 cases, anterior chamber reaction with or without fibrin reaction in 8 cases and rise of intraocular pressure in 3 cases. All complications were reversibile. Conclusion. Posterior capsule rupture/break is a serious complication of phacoemulsification, hardly to prevent. Regarding size of posterior rupture, foldable monoblock arteficial lens can be implanted into the sulcus on the remains of anterior capsule in most of the cases, keeping the advantages of small corneal incision: smaller astigmatism, better postoperative visual acuity, faster wound healing and earlier visual rehabilitation.

Background/Aim. Intensive epiphora (lacrimal apparatus disease) can make difficult daily routine and cause ocular refraction disturbances. In most cases ethiology is unknown, rarely occurs after nose surgical procedures, face fractures, in Wegener granulomatosis, sarcoidosis and malignancies. The aim of this study was to evaluate efficacy of endonasal endoscopic surgical procedure with the conventional surgical instruments in treatment of nasolacrimal obstructions. Methods. This retrospective study included 12 female patients with endonasal endoscopic surgical procedure from Otorhinological and Ophtalmological Departments of Military Medical Academy, Belgrade from September 2007 to April 2009. Preoperative nasal endoscopy was performed in order to reveal concomitant pathological conditions and anatomic anomalies which could make surgical procedure impossible. Computerized tomography was performed only in suspect nose diseases. Surgical endonasal endoscopic procedure was performed by otorhinolaryngologist and ophtalmologist in all patients. The patients had regular controls from 2 to 20 months. Results. A total of 12 female patients, age 34-83 years, were included in our study. Epiphora was a dominant symptom in all patients. In two patients deviation of nasal septum was found, and in other one conha bulosa at the same side as chronic dacryocystitis. All patients were subjected to endonasal dacryocystorhinostomy (DCR) by endoscopic surgical technique using conventional instruments. Concomitantly with DCR septoplastics in two patients and lateral lamictetomy in one patient were performed. There were no complications intraoperatively as well as in the immediate postoperative course. In two patients the need for reoperation occurred. Conclusion. Endoscopic DCR is minimally invasive and efficacious procedure for nasolacrymal obstructions performed by otorhinolaryngologist and ophtalmologist. Postoperative recovery is very fast.

INTRODUCTION Already in 1884, Knapp reported a successful cataract operation using 5% of cocaine in eyedrops. Today, different methods of local anesthesia in the operation of cataract are used, such as retrobulbary, peribulbary, subconjunctival, sub-tenon, topical and intracameral anesthesia. Phacoemulsification is a modern approach to the operation of cataract that is increasingly applied in our country. Aiming to eliminate the risk of severe complications caused by retrobulbary anesthesia, in our patients undergoing surgery to treat cataract we applied sub-tenon anesthesia. OBJECTIVE The aim of this work was to establish the efficacy and the safety of subtenal anesthesia in the operation of cataract using phacoemulsification technique. METHOD We examined 85 patients who were operated for cataract under sub-tenon anesthesia. The operation was performed using phacoemulsification technique. The surgeon injected about 2 ml of the mixture of lidocaine (2%) and bupivacaine (0.5%) in equal proportions into the bottom of the fornix at 11 o’clock or 1 o’clock position into one of the two upper eye quadrants. After phacoemulsification and the placement of intraocular lenses, the patients were asked to reply to the questions according to a standardized protocol. Priory, the patients were informed about the test and the pain scale ranging from 1 to 10, with 1 indicating the absence of pain and 10 unbearable pain. RESULTS Eighty-five patients underwent surgery for cataract using phacoemulsification technique and in whom posterior chamber intraocular lenses were placed under sub-tenon anesthesia. During the application of anesthesia, subjective pain experience was at the level of mild discomfort or non-existent in 3/4 of the patients. In relation to pain experience during surgery, it ranged from mild inconvenience to pain absence in 4/5 of the patients. The most frequent complication during surgery was eye rolling occurring in every 10th patient. In 4/5 patients the overall surgical course was assessed by the surgeon as excellent or outstanding. CONCLUSION Sub-tenon anesthesia applied at one point of the upper quadrant using during modern approach in the surgery of cataract, namely the phacoemulsification technique, offers good comfort to the patient during anesthesia introduction, as well as during surgery, with a relatively low complication rate occurring during the operation, and also offering good comfort to the surgeon.

Background/Aim. Esotropia is the most common manifestation form of strabism accompanied by refraction deviations and amblyopia. The aim of this prospective study was to present the outcomes of surgical treatment of esotropia in children and adolescents. Methods. Within the period from January 1st 2006 to February 1st 2007 at the Clinic for Ophtalmology, Military Medical Academy, Belgrade a total of 25 patients with esotropia (34 eyes) and previously corrected refraction anomaly and treated amblyopia were operated on. The patients were 4-19-year of age. All of the patients were submitted to a complete ophtalmologic and orthoptic examination prior to the surgery, and a month, three months and six months after the surgery. The surgery was performed under general anesthesia. Out of the total number of the patients nine were operated on both eyes, while 16 patients on one eye with amblyopia or frequent esodeviation. Nine patients were submitted to retroposition of the inner straight muscle, two to myectomy of the outer straight muscle, while in 14 of the patients a combination of retroposition and myectomy was performed. The patients were divided into three groups according to the preoperative angle at the distance and followed-up accordingly after the surgery. Deviation angle at the distance in the group I was 18-25 DP, in the group II 26-35 PD, while in the group III it was 36-60 PD. Results. The most numerous, group I (12 patients; 48%), a month following the surgery showed angle reduction by 55.58%, after three months 63.25%, and after six months 63.92%. The group II consisted of 8 patients (32%) showed angle reduction by 70.75% a month following the surgery, by 76% after three months, and by 79.12% after six months. The group III (5 patients; 20%) showed angle reduction by 72.20% a month following the surgery, 79.20 after three months, and 80.12% after six months following the surgery. Conclusion. The best postoperative outcomes after a month, three and six months were obtained in the group of patients with the highest esodeviation angle at the distance solved by the surgery on both eyes. Timely surgical treatment befell into major precondition for developing and maintaining the elements of binocular vision in the operated on patients. .

Introduction Glare can be defined as unpleasant sensation caused by a relatively strong source of light, which results in unpleasantness, discomfort and the lowering of optimal vision characteristics. It has been demonstrated that different factors influence the glare in pseudophakic subjects: opacity in vision media, the brightness of the pupil and the design of intraocular lenses. Objective The aim was to examine the influence of shine duration on glare in pseudophakic persons. Method We studied 152 eyes of 98 pseudophakic persons, aged from 50 to 70 years, with good vision acuity (0.8 and more) after final correction for far and near vision. The examination was conducted on the device Niktomat (Rodenstock Instrumente GMBH, Munchen-Hamburg) under the conditions of short and long shine. The source of light of 0.35 lux intensity, under the angle of 3 degrees, lightened the pupil for ten seconds in the first test, and continually in the second test. Results In the observed group, during a direct short tensecond shine, the sign on the screen with the contrast of 30% was seen by 140 eyes (92.1%), and in the control group the sign was seen by 88 eyes (97.8%). Under the direct continuous shine, normal findings were confirmed in 40 eyes (26.3%) of the observed group, and in 83 eyes (92.2%) of the control group. Conclusion In the observed pseudophakic persons, the duration of shine was found to be in correlation with glare.

Background/Aim. Trabeculectomy is a filtering antiglaucoma surgery performed to facilitate the formation of a drainage channel for the aqueous humor from the anterior chamber of the eye to the subconjunctival space making a collector, filtering cushion of the eye liquid. The cause of unfavourable outcome of trabeculectomy is episcleral fibrosis which leads to the obstruction of the drainage channel. Inflammatory reaction is an initial, but, also, the key event in the process of fibrosis and directly proportional to it. A successful medicamentous suppression of inflammation could stop fibrosis. Arccordingly, the aim of this study was to comparatively evaluate suppressing effects of capecitabine and 5-fluoroaracil upon inflammation, an initial fibrosis process after trabeculectomy. Methods. This study was performed on an experimental animal model, namely 24 rabbits (48 eyes), which were exposed to artificial cause of the tissue changes analogous to human subclinical inflammation. During the trabeculectomy, a 5% solution of 5- fluoroaracil was applied to the right eye sclera of a rabbit, while 2% solution of kapecitabine was applied to the left eye sclera, thus making possible to evaluate the effects of different drugs to the same animal. Two weeks after the surgery the subconjunctival - episcleral tissue cuts were analyzed. Semiquantitative histologic test was used to compare the cellular elements of inflammatory (fibroblasts, mononuclears, plasmocytes, eosinophiles), as well as fibrosing (colagen, reticulin fibers) process, and, based on the differences in histopathologic score, suppressive efficacy of 5-fluoroaracil and kapecitabine was evaluated and compared between the groups of the treated tissues. The results were shown as mean values ± standard deviation. Results. A statistically significantly lower score was revealed in the initial inflammatory cells - mononuclears and plasmocytes in the group of the tissues treated with kapecitabine, while there was no differences between the groups in the score of fibroblasts and colagen fibers. Conclusion. The suppression of the initial episcleral fibrosis process obtained by kapecitabine was more significant as compared to the suppression obtained by 5-fluoroaracil, thus providing more favorable outcome of the trabeculectomy. .

Background/Aim. Although an extraordinary visual acuity is achieved following the extracapsular cataract extraction with the implantation of intraocular lens, all the problems of vision are not solved in so doing and many of them should be considered. The aim of this study was to establish the influence of age, dioptric power of intraocular lens, corneal astigmatism and optic diameter of intraocular lens on glare in pseudophakic subjects. Methods. We examined 152 patients who underwent final correction at least two weeks after the suture removing what was performed if the astigmatism more than 2.0 D was measured by the use of a Javal keratometer. Examination was performed by a Rodenstock Adaptometer Nyctomat. According to the recommendation of the manufacturer, healthy persons should notice 50% of contrast under the constant glare and in the given time. Statistical data processing was performed by χ2 test. Results. In the group of patients with the findings lower than normal at constant glare there were 112 of eyes (73.68%) as follows: 22 eyes (14.47%) at the age from 50-55 years; 15 eyes (9.87%) were at the age from 56-60 years; 18 eyes (11.84%) were at the age from 61-65 years, and 57 eyes (37.50%) were at the age from 66-70 years. Dioptric power of lenses up to 20.0 D had 37 eyes (24.3%), from 20.5-22.0 D 85 eyes (56.9%) and more than 22.5 D, 27 eyes (17.8%). Regarding the results of discomfort caused by glare and corneal astigmatism, measured by a Javal keratometer, in the observed group normal results were found in 112 eyes (73.68%), and out of that number 95 (62.50%) were with corneal astigmatism less than 20.0 D, and 17 (11.18%) had astigmatism of 20.0 D and more. Out of 112 eyes there were 58 of them (38.16%) with findings lower than normal in relation to the constant glare and with the lens diameter of 5.5 mm, 48 (31.58%) with the lens diameter of 6.0mm, and 6 of them (3.95%) with lens diameter of 6.5mm. Conclusion. The study determined a significant statistical correlation between the dioptric power of lenses and the glare. The obtained results did not find out a significant increase in glare in relation to the age of subjects, optic diameter and corneal astigmatism.

Introduction. Solar retinopathy refers to retinal injury induced by direct or indirect solar viewing. Case report. We presented a patient who had observed partial solar eclipse 51 year before. He had bilaterally decreased vision and scar of the macular region at the time of presentation. The basic diagnostic tool applied in the presented patient, optical coherence tomography, showed hyporeflexivity of the outer retina in the segment of retinal pigment epithelialphotoreceptors complex with atrophy and thinning of the foveolar region. Conclusion. Optical coherence tomography is a powerful, non-invasive diagnostic tool which can ease the diagnosis and estimate the level and nature of the macular region damage.

Background: The use of artificial intelligence-driven code completion tools, particularly the integration of GitHub Copilot with Visual Studio, has potential implications for Health Informatics education, particularly for students learning SQL and Python., Objectives: This study aims to evaluate the effectiveness of these tools in solving or assisting with the solution of problems found in Health Informatics coursework, ranging from simple to complex., Methods: The study assesses the performance of GitHub Copilot in generating code for Health Informatics coding assignments from graduate classes, with a focus on the impact of detailed explanations on the tool's effectiveness., Results: Findings reveal that GitHub Copilot can generate correct code for straightforward problems. The correctness and effectiveness of solutions decrease with problem complexity, and the tool struggles with the most challenging problems, although performance on complex problems improves with more detailed explanations., Conclusions: The study underscores the relevance of these tools to programming in Health Informatics education but also highlights the need for critical evaluation by students. It concludes with a call for educators to adapt swiftly to this rapidly evolving technology., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: The use of electronic health records (EHRs) for clinical risk prediction is on the rise. However, in many practical settings, the limited availability of task-specific EHR data can restrict the application of standard machine learning pipelines. In this study, we investigate the potential of leveraging language models (LMs) as a means to incorporate supplementary domain knowledge for improving the performance of various EHR-based risk prediction tasks., Methods: We propose two novel LM-based methods, namely "LLaMA2-EHR" and "Sent-e-Med." Our focus is on utilizing the textual descriptions within structured EHRs to make risk predictions about future diagnoses. We conduct a comprehensive comparison with previous approaches across various data types and sizes., Results: Experiments across 6 different methods and 3 separate risk prediction tasks reveal that employing LMs to represent structured EHRs, such as diagnostic histories, results in significant performance improvements when evaluated using standard metrics such as area under the receiver operating characteristic (ROC) curve and precision-recall (PR) curve. Additionally, they offer benefits such as few-shot learning, the ability to handle previously unseen medical concepts, and adaptability to various medical vocabularies. However, it is noteworthy that outcomes may exhibit sensitivity to a specific prompt., Conclusion: LMs encompass extensive embedded knowledge, making them valuable for the analysis of EHRs in the context of risk prediction. Nevertheless, it is important to exercise caution in their application, as ongoing safety concerns related to LMs persist and require continuous consideration., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hospice care facilities are required to provide prescription drugs related to a hospice patient's terminal illness. From October 2010 to present, the Center for Medicare and Medicaid Services (CMS) has issued a series of communications regarding Medicare paying for hospice patients' prescription drugs under Part D that should be covered under the hospice Medicare Part A benefit. On April 4, 2011, CMS issued specific policy guidance to providers aimed at preventing inappropriate billing. While CMS has documented Part D prescription decreases in hospice patients, no research exists that connects these decreases and the policy guidance. This study aims to evaluate the effect of the April 4, 2011, policy guidance on hospice patients' Part D prescriptions. This study employed generalized estimating equations to assess (1) total monthly average prescriptions of all medications and (2) four categories of commonly prescribed hospice medications in pre-and-post policy guidance. This research used the Medicare claims of 113,260 Part D-enrolled Medicare male patients aged 66 and older between April 2009 and March 2013, including 110,547 non-hospice patients and 2713 hospice patients. Hospice patients' monthly average total Part D prescriptions decreased from 7.3 pre-policy guidance to 6.5 medications following the issuing of the guidance, while the four categories of hospice-specific medications decreased from .57 to .49. The findings of this study show that CMS's guidance issued to providers to prevent the inappropriate billing of hospice patients' prescriptions to the Part D benefit may lead to Part D prescription decreases as observed in this sample., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Inequitable access to leisure-time physical activity (LTPA) resources may explain geographic disparities in type 2 diabetes (T2D). We evaluated whether the neighborhood socioeconomic environment (NSEE) affects T2D through the LTPA environment., Research Design and Methods: We conducted analyses in three study samples: the national Veterans Administration Diabetes Risk (VADR) cohort comprising electronic health records (EHR) of 4.1 million T2D-free veterans, the national prospective cohort REasons for Geographic and Racial Differences in Stroke (REGARDS) (11 208 T2D free), and a case-control study of Geisinger EHR in Pennsylvania (15 888 T2D cases). New-onset T2D was defined using diagnoses, laboratory and medication data. We harmonized neighborhood-level variables, including exposure, confounders, and effect modifiers. We measured NSEE with a summary index of six census tract indicators. The LTPA environment was measured by physical activity (PA) facility (gyms and other commercial facilities) density within street network buffers and population-weighted distance to parks. We estimated natural direct and indirect effects for each mediator stratified by community type., Results: The magnitudes of the indirect effects were generally small, and the direction of the indirect effects differed by community type and study sample. The most consistent findings were for mediation via PA facility density in rural communities, where we observed positive indirect effects (differences in T2D incidence rates (95% CI) comparing the highest versus lowest quartiles of NSEE, multiplied by 100) of 1.53 (0.25, 3.05) in REGARDS and 0.0066 (0.0038, 0.0099) in VADR. No mediation was evident in Geisinger., Conclusions: PA facility density and distance to parks did not substantially mediate the relation between NSEE and T2D. Our heterogeneous results suggest that approaches to reduce T2D through changes to the LTPA environment require local tailoring., Competing Interests: Competing interests: DLL received investigator-initiated research support from Amgen, Inc for work unrelated to this manuscript. All other authors declare that they have no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

While every disease could affect a patient's prognosis, published studies continue to use indices that include a selective list of diseases to predict prognosis, which may limit its accuracy. This paper compares 6-month mortality predicted by a multimorbidity index (MMI) that relies on all diagnoses to the Deyo version of the Charlson index (DCI), a popular index that utilizes a selective set of diagnoses. In this retrospective cohort study, we used data from the Veterans Administration Diabetes Risk national cohort that included 6,082,018 diabetes-free veterans receiving primary care from January 1, 2008 to December 31, 2016. For the MMI, 7805 diagnoses were assigned into 19 body systems, using the likelihood that the disease will increase risk of mortality. The DCI used 17 categories of diseases, classified by clinicians as severe diseases. In predicting 6-month mortality, the cross-validated area under the receiver operating curve for the MMI was 0.828 (95% confidence interval of 0.826-0.829) and for the DCI was 0.749 (95% confidence interval of 0.748-0.750). Using all available diagnoses (MMI) led to a large improvement in accuracy of predicting prognosis of patients than using a selected list of diagnosis (DCI)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This prospective phase II clinical trial (Side Out 2) explored the clinical benefits of treatment selection informed by multi-omic molecular profiling (MoMP) in refractory metastatic breast cancers (MBCs). Core needle biopsies were collected from 32 patients with MBC at trial enrollment. Patients had received an average of 3.94 previous lines of treatment in the metastatic setting before enrollment in this study. Samples underwent MoMP, including exome sequencing, RNA sequencing (RNA-Seq), immunohistochemistry, and quantitative protein pathway activation mapping by Reverse Phase Protein Microarray (RPPA). Clinical benefit was assessed using the previously published growth modulation index (GMI) under the hypothesis that MoMP-selected therapy would warrant further investigation for GMI ≥ 1.3 in ≥ 35% of the patients. Of the 32 patients enrolled, 29 received treatment based on their MoMP and 25 met the follow-up criteria established by the trial protocol. Molecular information was delivered to the tumor board in a median time frame of 14 days (11-22 days), and targetable alterations for commercially available agents were found in 23/25 patients (92%). Of the 25 patients, 14 (56%) reached GMI ≥ 1.3. A high level of DNA topoisomerase I (TOPO1) led to the selection of irinotecan-based treatments in 48% (12/25) of the patients. A pooled analysis suggested clinical benefit in patients with high TOPO1 expression receiving irinotecan-based regimens (GMI ≥ 1.3 in 66.7% of cases). These results confirmed previous observations that MoMP increases the frequency of identifiable actionable alterations (92% of patients). The MoMP proposed allows the identification of biomarkers that are frequently expressed in MBCs and the evaluation of their role as predictors of response to commercially available agents. Lastly, this study confirmed the role of MoMP for informing treatment selection in refractory MBC patients: more than half of the enrolled patients reached a GMI ≥ 1.3 even after multiple lines of previous therapies for metastatic disease., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Importance: Diabetes causes substantial morbidity and mortality among adults in the US, yet its incidence varies across the country, suggesting that neighborhood factors are associated with geographical disparities in diabetes., Objective: To examine the association between neighborhood food environment and risk of incident type 2 diabetes across different community types (high-density urban, low-density urban, suburban, and rural)., Design, Setting, and Participants: This is a national cohort study of 4 100 650 US veterans without type 2 diabetes. Participants entered the cohort between 2008 and 2016 and were followed up through 2018. The median (IQR) duration of follow-up was 5.5 (2.6-9.8) person-years. Data were obtained from Veterans Affairs electronic health records. Incident type 2 diabetes was defined as 2 encounters with type 2 diabetes International Classification of Diseases, Ninth Revision or Tenth Revision codes, a prescription for diabetes medication other than metformin or acarbose alone, or 1 encounter with type 2 diabetes International Classification of Diseases Ninth Revision or Tenth Revision codes and 2 instances of elevated hemoglobin A1c (≥6.5%). Data analysis was performed from October 2020 to March 2021., Exposures: Five-year mean counts of fast-food restaurants and supermarkets relative to other food outlets at baseline were used to generate neighborhood food environment measures. The association between food environment and time to incident diabetes was examined using piecewise exponential models with 2-year interval of person-time and county-level random effects stratifying by community types., Results: The mean (SD) age of cohort participants was 59.4 (17.2) years. Most of the participants were non-Hispanic White (2 783 756 participants [76.3%]) and male (3 779 555 participants [92.2%]). The relative density of fast-food restaurants was positively associated with a modestly increased risk of type 2 diabetes in all community types. The adjusted hazard ratio (aHR) was 1.01 (95% CI, 1.00-1.02) in high-density urban communities, 1.01 (95% CI, 1.01-1.01) in low-density urban communities, 1.02 (95% CI, 1.01-1.03) in suburban communities, and 1.01 (95% CI, 1.01-1.02) in rural communities. The relative density of supermarkets was associated with lower type 2 diabetes risk only in suburban (aHR, 0.97; 95% CI, 0.96-0.99) and rural (aHR, 0.99; 95% CI, 0.98-0.99) communities., Conclusions and Relevance: These findings suggest that neighborhood food environment measures are associated with type 2 diabetes among US veterans in multiple community types and that food environments are potential avenues for action to address the burden of diabetes. Tailored interventions targeting the availability of supermarkets may be associated with reduced diabetes risk, particularly in suburban and rural communities, whereas restrictions on fast-food restaurants may help in all community types.

Purpose: The veterans administration diabetes risk (VADR) cohort facilitates studies on temporal and geographic patterns of pre-diabetes and diabetes, as well as targeted studies of their predictors. The cohort provides an infrastructure for examination of novel individual and community-level risk factors for diabetes and their consequences among veterans. This cohort also establishes a baseline against which to assess the impact of national or regional strategies to prevent diabetes in veterans., Participants: The VADR cohort includes all 6 082 018 veterans in the USA enrolled in the veteran administration (VA) for primary care who were diabetes-free as of 1 January 2008 and who had at least two diabetes-free visits to a VA primary care service at least 30 days apart within any 5-year period since 1 January 2003, or veterans subsequently enrolled and were diabetes-free at cohort entry through 31 December 2016. Cohort subjects were followed from the date of cohort entry until censure defined as date of incident diabetes, loss to follow-up of 2 years, death or until 31 December 2018., Findings to Date: The incidence rate of type 2 diabetes in this cohort of over 6 million veterans followed for a median of 5.5 years (over 35 million person-years (PY)) was 26 per 1000 PY. During the study period, 8.5% of the cohort were lost to follow-up and 17.7% died. Many demographic, comorbidity and other clinical variables were more prevalent among patients with incident diabetes., Future Plans: This cohort will be used to study community-level risk factors for diabetes, such as attributes of the food environment and neighbourhood socioeconomic status via geospatial linkage to residence address information., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This paper compares the accuracy of predicting suicide from Social Determinants of Health (SDoH) or history of illness., Population Studied: 5 313 965 Veterans who at least had two primary care visits between 2008 and 2016., Study Design: The dependent variable was suicide or intentional self-injury. The independent variables were 10 495 International Classification of Disease (ICD) Version 9 codes, age, and gender. The ICD codes included 40 V-codes used for measuring SDoH, such as family disruption, family history of substance abuse, lack of education, legal impediments, social isolation, unemployment, and homelessness. The sample was randomly divided into training (90 percent) and validation (10 percent) sets. Area under the receiver operating characteristic (AROC) was used to measure accuracy of predictions in the validation set., Principal Findings: Separate analyses were done for inpatient and outpatient codes; the results were similar. In the hospitalized group, the mean age was 67.2 years, and 92.1 percent were male. The mean number of medical diagnostic codes during the study period was 37; and 12.9 percent had at least one SDoH V-code. At least one episode of suicide or intentional self-injury occurred in 1.89 percent of cases. SDoH V-codes, on average, elevated the risk of suicide or intentional self-injury by 24-fold (ranging from 4- to 86-fold). An index of 40 SDoH codes predicted suicide or intentional self-injury with an AROC of 0.64. An index of 10 445 medical diagnoses, without SDoH V-codes, had AROC of 0.77. The combined SDoH and medical diagnoses codes also had AROC of 0.77., Conclusion: In predicting suicide or intentional self-harm, SDoH V-codes add negligible information beyond what is already available in medical diagnosis codes., Implications for Practice: Policies that affect SDoH (eg, housing policies, resilience training) may not have an impact on suicide rates, if they do not change the underlying medical causes of SDoH., (© 2020 The Authors. Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

Purpose: The greatest challenge in treating Clostridioides difficile infection (CDI) is disease recurrence, which occurs in about 20% of patients, usually within 30 days of treatment cessation. We sought to identify independent predictors of first recurrence among a national cohort of veterans with CDI., Methods: We conducted a case-control study among acute and long-term care Veterans Affairs (VA) inpatients and outpatients with a first CDI episode (positive stool sample for C. difficile toxin[s] and receipt of at least 2 days of CDI treatment) between 2010 and 2014. Cases experienced first recurrence within 30 days from the end of treatment. Controls were those without first recurrence matched 4:1 to cases on year, facility, and severity. Multivariable conditional logistic regression was used to identify predictors of first recurrence., Results: We identified 32 predictors of first recurrence among 974 cases and 3,896 matched controls. Significant predictors included medication use prior to (probiotics, fluoroquinolones, laxatives, third- or fourth-generation cephalosporins), during (first- or second-generation cephalosporins, penicillin/amoxicillin/ampicillin, third- and fourth-generation cephalosporins), and after CDI treatment (probiotics, any antibiotic, proton pump inhibitors [PPIs], and immunosuppressants). Other predictors included current biliary tract disease, malaise/fatigue, cellulitis/abscess, solid organ cancer, medical history of HIV, multiple myeloma, abdominal pain, and ulcerative colitis., Conclusion: In a large national cohort of outpatient and acute and long-term care inpatients, treatment with certain antibiotics, PPIs, immunosuppressants, and underlying disease were among the most important risk factors for first CDI recurrence., (Published by Oxford University Press on behalf of the American Society of Health-System Pharmacists 2019.)

Background: Exposure to antibiotics may increase the risk of type 2 diabetes. Veterans are at increased risk for diabetes and for exposure to antibiotics., Objective: To determine the impact of antibiotic exposure for risk of diabetes., Design: Retrospective cohort study., Participants: Veterans at the New York Harbor Healthcare System enrolled in primary care, 2004-2014, with ≥2 glycosylated hemoglobin test results <6.5%., Main Measures: The primary exposure was any antimicrobial prescribed >6 months prior to the date of diabetes diagnosis, loss to follow-up, death, or the end of the study, measured as the number of courses of antimicrobial prescriptions filled and the mean daily dose (MDD). The primary outcome was incident diagnosis of diabetes through 2014, defined ≥2 ICD-9 codes for diabetes or ≥2 prescriptions of diabetes medications, other than metformin. Cox proportional hazards regression was used to model antimicrobial medications, demographic and anthropometric measures, and comorbid cardiovascular conditions to incident diabetes. Models incorporated time varying covariates of antimicrobial medication and MDD to analyze associations by antimicrobial class., Key Results: Among 14,361 Veterans, 9922 (69.1%) were prescribed any antimicrobial medication during the study period. 1413 (9.8%) individuals developed type 2 diabetes. Increased risk of diabetes was associated with >1 prescription (HR 1.13 [1.01-1.26]) compared to none. Time varying analysis of the total number of cumulative courses prescribed showed increased diabetes risk for cephalosporin (HR 1.17 [1.04-1.31]), macrolide (HR 1.08 [1.03-1.13]) and penicillin (HR 1.05 [1.02-1.07]). MDD showed increased risk per 100-unit (mg) increase in antibiotic exposure from (HR 1.05 [1.02-1.08]) for sulfonamide to (HR 1.70 [1.51-1.92]) for cephalosporin., Conclusion: Any and repeated exposure to certain antibiotics may increase diabetes risk among Veterans. Results from this study add to the growing evidence suggesting that antibiotic exposure increases risk for diabetes. Antibiotic stewardship may be enhanced by better understanding this risk, and may lower the incidence of diabetes in populations at risk., (Published by Elsevier Ltd.)

United States Veterans are at excess risk for type 2 diabetes, but population differentials in risk have not been characterized. We determined risk of type 2 diabetes in relation to prediabetes and dyslipidemic profiles in Veterans at the VA New York Harbor (VA NYHHS) during 2004-2014. Prediabetes was based on American Diabetes Association hemoglobin A1c (HbA1c) testing cut-points, one of several possible criteria used to define prediabetes. We evaluated transition to type 2 diabetes in 4,297 normoglycemic Veterans and 7,060 Veterans with prediabetes. Cox proportional hazards regression was used to relate HbA1c levels, lipid profiles, demographic, anthropometric and comorbid cardiovascular factors to incident diabetes (Hazard Ratio [HR] and 95% confidence intervals). Compared to normoglycemic Veterans (HbA1c: 5.0-5.6%; 31-38 mmol/mol), risks for diabetes were >2-fold in the moderate prediabetes risk group (HbA1c: 5.7-5.9%; 39-41 mmol/mol) (HR 2.37 [1.98-2.85]) and >5-fold in the high risk prediabetes group (HbA1c: 6.0-6.4%; 42-46 mmol/mol) (HR 5.59 [4.75-6.58]). Risks for diabetes were increased with elevated VLDL (≥40mg/dl; HR 1.31 [1.09-1.58]) and TG/HDL (≥1.5mg/dl; HR 1.34 [1.12-1.59]), and decreased with elevated HDL (≥35mg/dl; HR 0.80 [0.67-0.96]). Transition to diabetes in Veterans was related in age-stratified risk score analyses to HbA1c, VLDL, HDL and TG/HDL, BMI, hypertension and race, with 5-year risk differentials of 62% for the lowest (5-year risk, 13.5%) vs. the highest quartile (5-year risk, 21.9%) of the risk score. This investigation identified substantial differentials in risk of diabetes in Veterans, based on a readily-derived risk score suitable for risk stratification for type 2 diabetes prevention., Competing Interests: The authors have declared that no competing interests exist.

Existing methods of screening for substance abuse (standardized questionnaires or clinician's simply asking) have proven difficult to initiate and maintain in primary care settings. This article reports on how predictive modeling can be used to screen for substance abuse using extant data in electronic health records (EHRs). We relied on data available through Veterans Affairs Informatics and Computing Infrastructure (VINCI) for the years 2006 through 2016. We focused on 4,681,809 veterans who had at least two primary care visits; 829,827 of whom had a hospitalization. Data included 699 million outpatient and 17 million inpatient records. The dependent variable was substance abuse as identified from 89 diagnostic codes using the Agency for Healthcare Quality and Research classification of diseases. In addition, we included the diagnostic codes used for identification of prescription abuse. The independent variables were 10,292 inpatient and 13,512 outpatient diagnoses, plus 71 dummy variables measuring age at different years between 20 and 90 years. A modified naive Bayes model was used to aggregate the risk across predictors. The accuracy of the predictions was examined using area under the receiver operating characteristic (AROC) curve in 20% of data, randomly set aside for the evaluation. Many physical/mental illnesses were associated with substance abuse. These associations supported findings reported in the literature regarding the impact of substance abuse on various diseases and vice versa. In randomly set-aside validation data, the model accurately predicted substance abuse for inpatient (AROC = 0.884), outpatient (AROC = 0.825), and combined inpatient and outpatient (AROC = 0.840) data. If one excludes information available after substance abuse is known, the cross-validated AROC remained high, 0.822 for inpatient and 0.817 for outpatient data. Data within EHRs can be used to detect existing or predict potential future substance abuse., Competing Interests: No competing financial interests exist.

Background: Though recurrent Clostridium difficile infection (CDI) is common and poses a major clinical concern, data are lacking regarding mortality among patients who survive their initial CDI and have subsequent recurrences. Risk factors for mortality in patients with recurrent CDI are largely unknown., Methods: Veterans Affairs patients with a first CDI (stool sample with positive C. difficile toxin(s) and ≥2 days CDI treatment) were included (2010-2014). Subsequent recurrences were defined as additional CDI episodes ≥14 days after the stool test date and within 30 days of the end of treatment. A matched (1:4) case-control analysis was conducted using multivariable conditional logistic regression to identify predictors of all-cause mortality within 30 days of the first recurrence., Results: Crude 30-day all-cause mortality rates were 10.6% for the initial CDI episode, 8.3% for the first recurrence, 4.2% for the second recurrence, and 5.9% for the third recurrence. Among 110 cases and 440 controls, 6 predictors of mortality were identified: use of proton pump inhibitors (PPIs; odds ratio [OR], 3.86; 95% confidence interval [CI], 2.14-6.96), any antibiotic (OR, 3.33; 95% CI, 1.79-6.17), respiratory failure (OR, 8.26; 95% CI, 1.71-39.92), congitive dysfunction (OR, 2.41; 95% CI, 1.02-5.72), nutrition deficiency (OR, 2.91; 95% CI, 1.37-6.21), and age (OR, 1.04; 95% CI, 1.01-1.07)., Conclusions: In our national cohort of Veterans, crude mortality decreased by 44% from the initial episode to the third recurrence. Treatment with antibiotics, use of PPIs, and underlying comorbidities were important predictors of mortality in recurrent CDI. Our study assists health care providers in identifying patients at high risk of death after CDI recurrence.

Background: Bio-ontologies are becoming increasingly important in knowledge representation and in the machine learning (ML) fields. This paper presents a ML approach that incorporates bio-ontologies and its application to the SEER-MHOS dataset to discover patterns of patient characteristics that impact the ability to perform activities of daily living (ADLs). Bio-ontologies are used to provide computable knowledge for ML methods to "understand" biomedical data., Results: This retrospective study included 723 cancer patients from the SEER-MHOS dataset. Two ML methods were applied to create predictive models for ADL disabilities for the first year after a patient's cancer diagnosis. The first method is a standard rule learning algorithm; the second is that same algorithm additionally equipped with methods for reasoning with ontologies. The models showed that a patient's race, ethnicity, smoking preference, treatment plan and tumor characteristics including histology, staging, cancer site, and morphology were predictors for ADL performance levels one year after cancer diagnosis. The ontology-guided ML method was more accurate at predicting ADL performance levels (P < 0.1) than methods without ontologies., Conclusions: This study demonstrated that bio-ontologies can be harnessed to provide medical knowledge for ML algorithms. The presented method demonstrates that encoding specific types of hierarchical relationships to guide rule learning is possible, and can be extended to other types of semantic relationships present in biomedical ontologies. The ontology-guided ML method achieved better performance than the method without ontologies. The presented method can also be used to promote the effectiveness and efficiency of ML in healthcare, in which use of background knowledge and consistency with existing clinical expertise is critical.

This article demonstrates how time-dependent, interacting, and repeating risk factors can be used to create more accurate predictive medicine. In particular, we show how emergence of anemia can be predicted from medical history within electronic health records. We used the Veterans Affairs Informatics and Computing Infrastructure database to examine a retrospective cohort of 9,738,838 veterans over an 11-year period. Using International Clinical Diagnoses Version 9 codes organized into 25 major diagnostic categories, we measured progression of disease by examining changes in risk over time, interactions in risk of combination of diseases, and elevated risk associated with repeated hospitalization for the same diagnostic category. The maximum risk associated with each diagnostic category was used to predict anemia. The accuracy of the model was assessed using a validation cohort. Age and several diagnostic categories significantly contributed to the prediction of anemia. The largest contributors were health status ([Formula: see text] = -1075, t = -92, p < 0.000), diseases of the endocrine ([Formula: see text] = -1046, t = -87, p < 0.000), hepatobiliary ([Formula: see text] = -1043, t = -72, p < 0.000), kidney ([Formula: see text] = -1125, t = -111, p < 0.000), and respiratory systems ([Formula: see text] = -1151, t = -89, p < 0.000). The AUC for the additive model was 0.751 (confidence interval 74.95%-75.26%). The magnitude of AUC suggests that the model may assist clinicians in determining which patients are likely to develop anemia. The procedures used for examining changes in risk factors over time may also be helpful in other predictive medicine projects.

Background: Accurate prediction of mortality for patients admitted to the intensive care units (ICUs) is an important component of medical care. However, little is known about the role of multimorbidity in predicting end of life for high-risk and vulnerable patients., Objective: The aim of the study was to derive and validate a multimorbidity risk model in an attempt to predict all-cause mortality at 6 and 12 months posthospital discharge., Methods: This is a retrospective, observational, clinical cohort study. Data were collected on 442,692 ICU patients who received care through the Veterans Administration between January 2003 and December 2013. The primary outcome was all-cause mortality at 6 and 12 months posthospital discharge. We divided the data into derivation (80%) and validation (20%) sets. Using multivariable logistic regression models, we compared prognostic models based on age, principal diagnosis groups, physiological markers, immunosuppressants, comorbidity categories, and a newly developed multimorbidity index (MMI) based on 5695 comorbidities. The cross-validated area under the receiver operating characteristic curve (AUC) was used to report the accuracy of predicting all-cause mortality at 6 and 12 months of hospital discharge., Results: The average age of patients was 68.87 years (standard deviation = 12.1), 95.9% were males, 44.9% were widowed, divorced, or separated. The relative order of accuracy in predicting mortality was the MMI (AUC = 0.84, CI = 0.83-0.84), VA Inpatient Evaluation Center index (AUC = 0.80, CI = 0.79-0.81), principal diagnosis groups (AUC = 0.74, CI = 0.73-0.74), comorbidities (AUC = 0.69, CI = 0.68-0.70), physiological markers (AUC = 0.65, CI = 0.64-0.65), age (AUC = 0.60, CI = 0.60-0.61),and immunosuppressant use (AUC = 0.59, CI = 0.58-0.59)., Conclusions: The MMI improved the accuracy of predicting short- and long-term all-cause mortality for ICU patients. Further prospective studies are needed to validate the index in different clinical settings and test generalizability of results in patients outside the VA system of care.

Problems/objectives: Septoplasty is a frequently performed ENT surgical procedure and anatomical reference points are well established. Nevertheless, it can be associated with serious complications., Methodology: We report on a 27-year-old female patient, who was admitted to our hospital 16 days after septoplasty in another institution. She complained of vision loss in her left eye and yellowish discharge from the nose. The MSCT scan revealed fracture of the upper and lateral walls of the left sphenoid sinus with the bone fragment penetrating the left optic canal and signs of left maxillary, ethmoid, and sphenoid sinusitis. During functional endoscopic sinus surgery, a lesion of the left optic canal was clearly seen., Results: Despite many treatments, the patient was released from our hospital without any residual sight in her left eye., Conclusion: Unilateral blindness is a rare, but devastating complication following septoplasty.