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The European Bioinformatics Institute (EMBL-EBI) maintains a comprehensive range of freely available and up-to-date molecular data resources, which includes over 40 resources covering every major data type in the life sciences. This year's service update for EMBL-EBI includes new resources, PGS Catalog and AlphaFold DB, and updates on existing resources, including the COVID-19 Data Platform, trRosetta and RoseTTAfold models introduced in Pfam and InterPro, and the launch of Genome Integrations with Function and Sequence by UniProt and Ensembl. Furthermore, we highlight projects through which EMBL-EBI has contributed to the development of community-driven data standards and guidelines, including the Recommended Metadata for Biological Images (REMBI), and the BioModels Reproducibility Scorecard. Training is one of EMBL-EBI's core missions and a key component of the provision of bioinformatics services to users: this year's update includes many of the improvements that have been developed to EMBL-EBI's online training offering., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Competing Interests: Competing interests The authors declare no competing or financial interests.

Background: Published studies evaluating the effect of robotic assistance on clinical outcomes and costs of care in diaphragmatic hernia repair (DHR) have been limited., Study Design: The Healthcare Cost and Utilization Project State Inpatient and State Ambulatory Surgery and Services Databases for Florida were queried to identify patients undergoing transabdominal DHR between 2011 and 2018 and associated inpatient and outpatient encounters within 12 months after the index operation. Patients undergoing robotic DHR were 1:1:1 propensity score-matched for age, sex, race, Elixhauser comorbidity score, case priority, payer, and facility volume with patients undergoing open and laparoscopic DHR., Results: There were 5,962 patients (67.3%) who underwent laparoscopic DHR, 1,520 (17.2%) who underwent open DHR, and 1,376 (15.5%) who underwent robotic DHR. On comparison of matched cohorts, median index length of stay (3 days; interquartile range [IQR] 2 to 5 days vs 2 days; IQR 1 to 4 days; p < 0.001) and index hospitalization costs ($17,236; IQR $13,231 to $22,183 vs $12,087; IQR $8,881 to $17,439; p < 0.001) for robotic DHR were greater than for laparoscopic DHR. Median length of stay for open DHR (6 days; IQR 4 to 10 days) was longer than that for both laparoscopic and robotic DHR. Median index hospitalization costs for open DHR ($16,470; IQR $11,152 to $23,768) were greater than those for laparoscopic DHR, but less than those for robotic DHR. There were no significant differences between cohorts in the overall rate of post-index care., Conclusions: Laparoscopic DHR is the most cost-effective approach to DHR. Robotic assistance provides clinical outcomes comparable with laparoscopic DHR, but is associated with increased index cost., (Copyright © 2021 American College of Surgeons. All rights reserved.)

Background: Total abdominal colectomy (TAC) is a treatment modality of last recourse for patients with severe and/or refractory ulcerative colitis (UC). The goal of this study is to evaluate temporal trends and treatment outcomes following TAC among hospitalized UC patients in the biologic era., Methods: We queried the National Inpatient Sample (NIS) to identify patients older than 18 years with a primary diagnosis of ulcerative colitis (UC) who underwent TAC between 2002 and 2013. We evaluated postoperative morbidity and mortality as outcomes of interest. Logistic regression was used to explore factors associated with postoperative morbidity and mortality after TAC., Results: A weighted total of 307,799 UC hospitalizations were identified. Of these, 27,853 (9%) resulted in TAC. Between 2002 and 2013, hospitalizations for UC increased by over 70%; however, TAC rates dropped significantly from 111.1 to 77.1 colectomies per 1000 UC admissions. Overall, 2.2% of patients died after TAC. Mortality rates after TAC decreased from 3.5% in 2002 to 1.4% in 2013. Conversely, morbidity rates were stable throughout the study period. UC patients with emergent admissions, higher comorbidity scores and who had TAC in low volume colectomy hospitals had poorer outcomes. Regardless of admission type, outcomes were worse if TAC was performed more than 24 h after admission., Conclusions: Despite increased hospitalizations for UC, rates of TAC have declined during the post-biologic era. For UC patients who undergo TAC, mortality has declined significantly while morbidity remains stable. Older age, race, emergent admissions and delayed surgery are predictive factors of both postoperative morbidity and mortality.

Objective: To summarize overall patterns of the impact of neighborhood socioeconomic status (nSES) on stroke incidence and uncover potential gaps in the literature, we conducted a systematic review of studies examining the association between nSES and stroke incidence, independent of individual SES., Methods: Four electronic databases and reference lists of included articles were searched, and corresponding authors were contacted to locate additional studies. A keyword search strategy included the 3 broad domains of neighborhood, SES, and stroke. Eight studies met our inclusion criteria (e.g., nSES as an exposure, individual SES as a covariate, and stroke incidence as an outcome). We coded study methodology and findings across the 8 studies., Results: The results provide evidence for the overall nSES and stroke incidence association in Sweden and Japan, but not within the United States. Findings were inconclusive when examining the nSES-stroke incidence association stratified by race. We found evidence for the mediating role of biological factors in the nSES-stroke incidence association., Conclusions: Higher neighborhood disadvantage was found to be associated with higher stroke risk, but it was not significant in all the studies. The relationship between nSES and stroke risk within different racial groups in the United States was inconclusive. Inconsistencies may be driven by differences in covariate adjustment (e.g., individual-level sociodemographic characteristics and neighborhood-level racial composition). Additional research is needed to investigate potential intermediate and modifiable factors of the association between nSES and stroke incidence, which could serve as intervention points., (© 2021 American Academy of Neurology.)

Adolescents comprise one fourth of the world's population, with about 90% of them living in low- and middle-income countries (LMICs). The incidence of depression markedly increases during adolescence, making the disorder a leading cause of disease-related disability in this age group. However, most research on adolescent depression has been performed in high-income countries (HICs). To ascertain the extent to which this disparity operates in neuroimaging research, a systematic review of the literature was performed. A total of 148 studies were identified, with neuroimaging data available for 4,729 adolescents with depression. When stratified by income group, 122 (82%) studies originated from HICs, while 26 (18%) were conducted in LMICs, for a total of 3,705 and 1,024 adolescents with depression respectively. A positive Spearman rank correlation was observed between country per capita income and sample size (r s =0.673, p = 0.023). Our results support the previous reports showing a large disparity between the number of studies and the adolescent population per world region. Future research comparing neuroimaging findings across populations from HICs and LMICs may provide unique insights to enhance our understanding of the neurobiological processes underlying the development of depression., Competing Interests: Declaration of Competing Interest Drs. Battel, Cunegatto, Viduani, Fisher, Kohrt, Swartz, and Kieling report no competing interests. Dr. Mondelli has received research funding from Johnson & Johnson, a pharmaceutical company interested in the development of anti-inflammatory strategies for depression, but the research described in this paper is unrelated to this funding., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Spinal meningiomas constitute the majority of primary spinal neoplasms, yet their pathogenesis remains elusive. By investigating the distribution of these tumors across sociodemographic variables can provide direction in etiology elucidation and healthcare disparity identification., Methods: To investigate benign and malignant spinal meningioma incidences (per 100,000) with respect to sex, age, income, residence, and race/ethnicity, we queried the largest American administrative dataset (1997-2016), the National (Nationwide) Inpatient Sample (NIS), which surveys 20% of United States (US) discharges., Results: Annual national incidence was 0.62 for benign tumors and 0.056 for malignant. For benign meningiomas, females had an incidence of 0.81, larger (P=0.000004) than males at 0.40; yet for malignant meningiomas, males had a larger (P=0.006) incidence at 0.062 than females at 0.053. Amongst age groups, peak incidence was largest for those 65-84 years old (2.03) in the benign group, but 45-64 years old (0.083) for the malignant group. For benign and malignant meningiomas respectively, individuals with middle/high income had an incidence of 0.67 and 0.060, larger (P=0.000008; P=0.04) than the 0.48 and 0.046 of low income patients. Incidences were statistically similar (P=0.2) across patient residence communities. Examining race/ethnicity (P=0.000003) for benign meningiomas, incidences for Whites, Asian/Pacific Islanders, Hispanics, and Blacks were as follows, respectively: 0.83, 0.42, 0.28, 0.15., Conclusions: Across sociodemographic strata, healthcare inequalities were identified with regards to spinal meningiomas. For benign spinal meningiomas, incidence was greatest for patients who were female, 65-84 years old, middle/high income, living in rural communities, White, and Asian/Pacific Islander. Meanwhile, for malignant spinal meningiomas incidence was greatest for males, those 45-65 years old, and middle/high income., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Occipitocervical fusion (OCF) procedures are increasing due to an aging population and the prevalence of trauma, rheumatoid arthritis, and tumors. Reoperation rates and readmission risk factors for cervical fusions have been established, but in relation to OCF they have not been explored. This study investigates the patterns of readmissions and complications following OCF using a national database., Methods: The 2016 U.S. Nationwide Readmissions Database was used for sample collection. Adults (>18 years) who underwent OCF were identified using the 2016 ICD-10 coding system, and we examined the readmission rates (30-day and 90-day) and reoperation rates., Results: Between January and September 2016, a total of 477 patients underwent OCF; the 30-day and 90-day readmission rates were 10.4% and 22.4%, respectively. The 90-day reoperation rate related to the index surgery was 5.7%. Mean age (68.58 years) was significantly greater in the readmitted group versus nonreadmitted group (61.76 years) (P < 0.001). The readmitted group had a significantly higher Charlson Comorbidity Index and Elixhauser Comorbidity Index (5.00 and 2.41, respectively) than the nonreadmitted group (3.25 and 1.15, respectively; P < 0.001). Nonelective OCF showed a higher readmission rate (29.18%) versus elective OCF (12.23%) (P < 0.001). Medicare and Medicaid patients showed the highest rates of readmission (27.27% and 20.41%, respectively). Readmitted patients had higher total health care costs., Conclusions: Nonelective OCF was found to have a readmission rate of almost 2½× that of elective OCF. Understanding risk factors associated with OCF will help with operative planning and patient optimization., (Copyright © 2020 Elsevier Inc. All rights reserved.)

International trade is one of the classic areas of study in economics. Its empirical analysis is a complex problem, given the amount of products, countries and years. Nowadays, given the availability of data, the tools used for the analysis can be complemented and enriched with new methodologies and techniques that go beyond the traditional approach. This new possibility opens a research gap, as new, data-driven, ways of understanding international trade, can help our understanding of the underlying phenomena. The present paper shows the application of the Latent Dirichlet allocation model, a well known technique in the area of Natural Language Processing, to search for latent dimensions in the product space of international trade, and their distribution across countries over time. We apply this technique to a dataset of countries' exports of goods from 1962 to 2016. The results show that this technique can encode the main specialisation patterns of international trade. On the country-level analysis, the findings show the changes in the specialisation patterns of countries over time. As traditional international trade analysis demands expert knowledge on a multiplicity of indicators, the possibility of encoding multiple known phenomena under a unique indicator is a powerful complement for traditional tools, as it allows top-down data-driven studies., Competing Interests: The authors have declared that no competing interests exist.

Background: While considered a safe operation, deep brain stimulation (DBS) has been associated with various morbidities. We assessed differences in postsurgical complication rates in patients undergoing the most common types of neurostimulation surgery., Methods: The National Readmission Database (NRD) was queried to identify patients undergoing neurostimulation placement with the diagnosis of Parkinson disease (PD), epilepsy, dystonia, or essential tremor (ET). Demographics and complications, including infection, pneumonia, and neurostimulator revision, were queried for each cohort and compiled. Readmissions were assessed in 30-, 90-, and 180-day intervals. We implemented nearest-neighbor propensity score matching to control for demographic and sample size differences between groups., Results: We identified 3230 patients with Parkinson disease, 1289 with essential tremor, 965 with epilepsy, and 221 with dystonia. Following propensity score matching, 221 patients remained in each cohort. Readmission rates 30-days after hospital discharge for PD patients (15.5 %) were significantly greater than those for ET (7.8 %) and seizure patients (4.4 %). Pneumonia was reported for PD (1.6 %), seizure (3.3 %) and dystonia (1.7 %) patients but not individuals ET. No PD patients were readmitted at 30-days due to dysphagia while individuals treated for ET (6.5 %), seizure (1.6 %) and dystonia (5.2 %) were. DBS-revision surgery was performed for 11.48 % of PD, 6.52 % of ET, 1.64 % of seizure and 6.90 % of dystonia patients within 30-days of hospital discharge., Conclusion: 30-day readmission rates vary significantly between indications, with patients receiving DBS for PD having the highest rates. Further longitudinal studies are required to describe drivers of variation in postoperative outcomes following DBS surgery for different indications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The objective of the study is to review the literature for studies that assessed the concordance of financial conflicts of interest disclosures with payments' databases and evaluate their methods., Study Design and Setting: We conducted a systematic survey of the health literature to identify eligible studies. We searched both Medline and EMBASE up to February 2017. We conducted study selection, data abstraction, and methodological quality assessment in duplicate and independently using standardized forms. We subcategorized 'nonconcordant disclosures' as either 'partially nonconcordant' or 'completely nonconcordant'. The main outcome was the percentage of authors with 'nonconcordant' disclosures. We summarized results by three levels of analysis: authors, companies, and studies., Results: We identified 27 eligible journal articles. The top two types of documents assessed were published articles (n = 13) and published guidelines (n = 9). The most commonly used payment database was the Open Payments Database (n = 16). The median percentage of authors with 'nonconcordant' disclosures was 81%; the median percentage was 43% for 'completely nonconcordant' disclosures. The percentage of 'nonconcordant' conflict of interest (COI) reporting by companies varied between 23% and 85%. The methods of concordance assessment, as well as the labeling and definitions of assessed outcomes varied widely across the included studies. We judged three of the included studies as high-quality studies., Conclusion: Underreporting of health science researchers' financial COIs is pervasive. Studies assessing COI underreporting suffer from a number of limitations that could have overestimated their findings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Every year, there are an estimated 22.6 million new neurosurgical consultative cases worldwide, of which 13.8 million require surgery. In 2016, the global neurosurgical workforce was estimated and mapped as open-access information to guide neurosurgeons, affiliates, and policy makers. We present a subsequent investigation for mapping the global neurosurgical workforce for 2018 to show the replicability of previous data collection methods as well as to show any changes in workforce density., Methods: We extracted data on the absolute number of neurosurgeons per low and middle-income countries (LMICs) in 2016 from the database of the global neurosurgical workforce mapping project. The estimated number of neurosurgeons in each LMIC during 2018 was obtained from collaborators. The median workforce densities were calculated for 2016 and 2018. Neurosurgical workforce density heat maps were generated., Results: We received data from 119 countries (response rate 86.2%) and imputed data for 19 countries (13.8%). Seventy-eight (56.5%, N = 138) countries had an increase in their number of neurosurgeons, 9 (6.5%) showed a decrease, whereas 51 (37.0%) had the same number of neurosurgeons in both years. The pooled median increased from 0.17 (interquartile range, 0.54) in 2016 to 0.18 (interquartile range, 0.59) in 2018., Conclusions: Overall, the density of the neurosurgical workforce has increased from 2016 to 2018. However, at the current rate, 80 LMICs (58.0%) will not meet the neurosurgical workforce density target by 2030., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Little is known about the economic burden of treatment-resistant depression (TRD) in patients with physical conditions., Objective: To assess health care resource utilization (HRU) and costs, work loss days, and related costs in patients with TRD and physical conditions versus patients with the same conditions and non-TRD major depressive disorder (MDD) or without MDD., Methods: Adults aged < 65 years with MDD treated with antidepressants were identified in the OptumHealth Care Solutions database (July 2009-March 2017). Patients who received a diagnosis of MDD and initiated a third antidepressant regimen (index date) after 2 regimens of adequate dose and duration were defined as having TRD. Patients with non-TRD MDD and without MDD were assigned a random index date. Patients with < 6 months of continuous health plan eligibility pre- or post-index; a diagnosis of psychosis, schizophrenia, bipolar disorder/mania, dementia, and developmental disorders; and/or no baseline physical conditions (cardiovascular, metabolic, and respiratory disease or cancer) were excluded. Patients with TRD were matched 1:1 to each of the non-TRD MDD and non-MDD cohorts based on propensity scores. Per patient per year HRU, costs, and work loss outcomes were compared up to 24 months post-index date using negative binominal and ordinary least square regressions., Results: A total of 2,317 patients with TRD (mean age, 47.6 years; 63.1%, female; mean follow-up, 19.7 months) had ≥ 1 co-occurring key physical condition (cardiovascular, 52.5%; metabolic, 48.2%; respiratory, 16.4%; and cancer, 9.5%). Relative to non-TRD MDD and non-MDD cohorts, respectively, patients with TRD had 46% and 235% more inpatient admissions, 28% and 128% more emergency department visits, and 53% and 155% more outpatient visits (all P < 0.05). Health care costs were $22,541 in the TRD cohort, $17,450 in the non-TRD MDD cohort, and $10,047 in the non-MDD cohort, yielding cost differences of $5,091 (vs. non-TRD MDD) and $12,494 (vs. non-MDD; all P < 0.01). In patients with work loss data available (n = 278/cohort), those with TRD had 2.0 and 2.9 times more work loss as well as $8,676 and $10,323 higher work loss costs relative to those with non-TRD MDD and without MDD, respectively (all P < 0.001)., Conclusions: In patients with physical conditions, those with TRD had higher HRU and health care costs, work loss days, and associated costs compared with non-TRD MDD and non-MDD cohorts., Disclosures: This study was sponsored by Janssen Scientific Affairs (JSA), which was involved in all aspects of the research, including the design of the study; the collection, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. Joshi and Daly are employed by JSA. Zhdanava, Pilon, Rossi, Morrison, and Lefebvre are employees of Analysis Group, which received funding from JSA for conducting this study and has received consulting fees from Novartis Pharmaceuticals and GSK, unrelated to this study. Kuvadia is employed by Integrated Resources, which has provided research services to JSA unrelated to this study; Joshi reports past employment by and stock ownership in Johnson & Johnson; Nelson reports advisory board, data and safety monitoring board, and consulting fees from Assurex, Eisai, FSV-7, JSA, Lundbeck, Otsuka, and Sunovion and royalties from UpToDate, unrelated to this study. This work was presented at AMCP Nexus 2019, held in National Harbor, MD, from October 29 to November 1, 2019.

Background: Flow diverters (FDs) have marked the beginning of innovations in the endovascular treatment of large unruptured intracranial aneurysms, but no multi-institutional studies have been conducted on these devices from both the clinical and economic perspectives., Objective: To compare retreatment rates and healthcare expenditures between FDs and conventional coiling-based treatments in all eligible cases in Japan., Methods: We identified patients who had undergone endovascular treatments during the study period (October 2015-March 2018) from a national-level claims database. The outcome measures were retreatment rates and 1-yr total healthcare expenditures, which were compared among patients who had undergone FD, coiling, and stent-assisted coiling (SAC) treatments. The coiling and SAC groups were further categorized according to the number of coils used. Retreatment rates were analyzed using Cox proportional hazards models, and total expenditures were analyzed using multilevel mixed-effects generalized linear models., Results: The study sample comprised 512 FD patients, 1499 coiling patients, and 711 SAC patients. The coiling groups with ≥10 coils and ≥9 coils had significantly higher retreatment rates than the FD group with hazard ratios of 2.75 (1.30-5.82) and 2.52 (1.24-5.09), respectively. In addition, the coiling group with ≥10 coils and SAC group with ≥10 coils had significantly higher 1-year expenditures than the FD group with cost ratios (95% CI) of 1.30 (1.13-1.49) and 1.31 (1.15-1.50), respectively., Conclusion: In this national-level study, FDs demonstrated significantly lower retreatment rates and total expenditures than conventional coiling with ≥ 9 coils., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background: In the United States, the incidence of acute myeloid leukemia (AML) has steadily increased over the last decade; in 2019, it was estimated that AML would affect 21,450 new patients and lead to 10,920 deaths. Detailed real-world cost estimates and comparisons of key AML treatment episodes, such as in high-intensity chemotherapy (HIC), low-intensity chemotherapy (LIC), hematopoietic stem cell transplantation (HSCT), and relapsed/refractory (R/R), are scarce in the commercially insured U.S., Objective: To examine health resource utilization (HRU), clinical burden, and direct health care costs across various AML treatment episodes in a large sample of commercially insured U.S., Methods: A retrospective cohort analysis was conducted. Patients with newly diagnosed AML were followed to identify the key active treatment episodes across the course of their disease. Data were obtained from 2 sources: IQVIA's Real-World Data (RWD) Adjudicated Claims Database - U.S. (formerly known as PharMetrics Plus), which comprises adjudicated claims for more than 150 million unique enrollees across the United States, and IQVIA Charge Detail Master Hospital Database, which has detailed data regarding services received in an inpatient setting. Calculation of all-cause HRU was based on physician office visits, nonphysician office visits, emergency department visits, inpatient visits, and outpatient pharmacy utilization. Calculation of all-cause health care costs was based on total allowed costs and reported by the following cost components: physician office visits, nonphysician office visits, emergency department visits, inpatient visits, and outpatient pharmacy utilization. Symptom and toxicity events were estimated via proxies such as diagnosis codes, procedures, and treatments administered., Results: The final study sample consisted of 1,542 HIC-induction (HIC-I), 591 HIC-consolidation (HIC-C), 628 LIC, 1,000 patients with HSCT, and 707 patients with R/R AML. Total mean episode costs were highest in R/R episodes ($439,104), followed by HSCT ($329,621), HIC-I ($198,657), HIC-C ($73,428), and LIC ($53,081) episodes. Across all treatment episodes, hospitalization was the largest contributor to cost with mean hospitalization costs ranging from $308,978 in the R/R setting to $49,580 for patients receiving LIC; of these, costs related to intensive care unit admission were a noteworthy contributor. In patients with R/R AML and HSCT, expenditures related to pharmacy utilization averaged $24,640 and $12,203, respectively, and expenditures related to physician office visits averaged $10,926 and $6,090, respectively; these expenditures were much lower across other episodes. Across all categories of symptom and toxicity events, cardiovascular events was the only category of event that was a significant predictor of higher cost across all episodes. Symptom and toxicity events commonly associated with AML were associated with significantly increased costs, especially in R/R episodes., Conclusions: This resource utilization and direct health care cost analysis highlights the substantial economic burden associated with key AML treatment episodes in the United States, specifically during HIC-I, HSCT, and R/R episodes., Disclosures: This study was funded by Astellas Pharma. Astellas employees were involved in the study design, interpretation of data, writing of the manuscript, and the decision to submit the manuscript for publication. Pandya and Wilson are employees of Astellas Pharma U.S. Walsh was an employee of Astellas Pharma U.S. while the study was conducted. Chen, McGuiness, and Wade are employees of IQVIA, which received funding from Astellas Pharma U.S. Madeiros was employed at Stanford University while this study was conducted and received a consulting fee from Astellas for work on this study. Data discussed in this study were previously presented at the 59th Annual American Society for Hematology Meeting & Exposition, 2017; December 9-12, 2017; Atlanta, GA.

Objectives: To evaluate the patterns of financial transaction between industry and urologists in the first 5 years of reporting in the Open Payments Program (OPP) by comparing transactions over time, between academic and nonacademic urologists, and by provider characteristics among academic urologists., Methods: The Center for Medicare & Medicaid Services OPP database was queried for General Payments to urologists from 2014-2018. Faculty at ACGME-accredited urology training programs were identified and characterized via publicly available websites. Industry transfers were analyzed by year, practice setting (academic vs nonacademic), provider characteristics, and AUA section. Payment nature and individual corporate contributions were also summarized., Results: A total of 12,521 urologists - representing 75% of the urology workforce in any given year - received $168 million from industry over the study period. There was no significant trend in payments by year (P = .162). Urologists received a median of $1602 over the study period, though 14% received >$10,000. Payment varied significantly by practice setting (P <.001), with nonacademic urologists receiving more but smaller payments than academic urologists. Among academic urologists, gender (P <.001), department chair status (P <.001), fellowship training (P <.001), and subspecialty (P <.001) were significantly associated with amount of payment from industry. Annual payments from industry varied significantly by AUA section., Conclusion: Reporting of physician-industry transactions has not led to a sustained decline in transactions with urologists. Significant differences in industry interaction exist between academic and nonacademic urologists, and values transferred to academic urologists varied by gender, chair status, subspecialty, and AUA section., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To identify whether institutions with strong conflicts of interest (COI) policies receive less industry payments than those with weaker policies. While industry-physician interactions can have collaborative benefits, financial COI can undermine preservation of the integrity of professional judgment and public trust. To address this concern, academic institutions have adopted COI policies. It is unclear whether the strength of COI policy correlates with industry payments in urology., Materials and Methods: 131 US academic urology programs were surveyed on their COI policies, and graded according to the American Medical Student Association (AMSA) criteria. Strength of COI policy was compared against industry payments in the Center for Medicare and Medicaid Services Open Payments database., Results: Fifty-seven programs responded to the survey, for a total response rate of 44%. There was no difference between COI policy groups on total hospital payments (P = .05), total department payments (P = .28), or dollars per payment (P = .57). On correlation analysis, there was a weak but statistically nonsignificant correlation between AMSA Industry Policy Survey Score and Open Payments payments (ρ = -0.14, P = .32)., Conclusion: Strength of conflicts of interest policy in academic urology did not correlate to industry payments within the Open Payments database. Establishment of strong COI policy may create offsetting factors that mitigate the intended effects of the policy. Further studies will be required to develop the evidence base for policy design and implementation across various specialties., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose of Review: The aim of this article is to characterize the present state-of-the-art on the topic of food allergies across Europe., Recent Findings: A systematic review and metaanalysis on the epidemiology of food allergy in Europe have been performed by the Food Allergy and Anaphylaxis Guidelines Group of the European Academy of Allergology and Clinical Immunology. The authors had made an extensive search of four different electronic databases which retrieved thousands of hits. A critical appraisal of the documents reduced their number to just over 100 articles covering the period 2000-2012, revealing striking methodological inhomogeneity and blank areas on the map of the continent, particularly for the adult population. A major new development intending to fill in the gaps in the field of food allergy is the launch and implementation of the European Union-funded project 'Prevalence, Cost and Basis of Food Allergy Across Europe,' acronym 'EuroPrevall.' Among the deliverable of the project are several seminal articles on food allergy in adults which are presented in this review., Summary: The EuroPrevall project confirmed much more reliably and in more detail the existing inhomogeneity in the prevalence of food allergy, which reflects environmental and climate differences between the separate countries, but possibly also the level of public awareness.

Background: Previous reports have suggested an increasing rate of utilization of spinal fusions, but contemporary data have not been analyzed, and there has been little investigation of putative drivers of increased utilization., Objective: To investigate whether there is an ongoing trend of increased utilization of spinal fusions in recent data, and if there may be associations with an increasing proportion of elderly in the population, changing patterns of payer-types, and changing reimbursement rates., Methods: We analyze 7.1 million cases from the National Inpatient Sample between 1998 and 2014. We measure annual utilization per 100 000 persons and conduct trend analyses with subgroup analysis of the senior (65 + ) population. Spine surgery utilization is compared with nonspine surgical procedures (coronary artery bypass grafting, hernia repair, hip, and knee replacement). We assess trends in charges, payer type, Medicare reimbursement rates, and hospital type., Results: There was an 88% increase in the utilization rate of spinal fusion procedures from 1998 to 2014 (from 74 to 139 cases per 100 000 persons) with a significant upward trend (P < .001) that persisted in the 65 + subgroup (P < .001). An increasing proportion of spinal fusions is paid for by public payers, but per-procedure reimbursement for spinal fusions by Medicare has decreased recently (5% reduction from 2014 to 2016)., Conclusion: Utilization of spinal fusions continues to increase and is not explained by increased proportion of elderly in the population, increased utilization of surgeries across specialties, or increased Medicare reimbursement. In fact, increased utilization of spinal fusions temporally correlated with decreasing per-procedure Medicare reimbursement., (Copyright © 2019 by the Congress of Neurological Surgeons.)

A trend towards charging for access to research findings, tools and databases is becoming more prominent globally. But charging for the use of research tools and databases that are vital to research supporting national and international policy development might be unjustified. Financial barriers to accessing these tools and databases disproportionately affect low- and middle-income countries, who may have greater need for information that fuels research in their areas of concern. However, changing this trend is potentially possible. One example is the experience with the EuroQol-five-dimensional questionnaire (EQ-5D), a generic measure of health status used in economic evaluations for resource allocation decisions. Increasingly, governments and health-care providers are using the EQ-5D tool in patient-reported outcome measures to monitor quality of health-care provision, diagnose and track disease progression, and involve patients in their health care. The EuroQol Group, which owns the intellectual property rights to the EQ-5D, recently terminated their policy of charging for noncommercial, nonresearch uses of the tool. We share a brief history of this development and examine these charging policies in the context of the EQ-5D's use in national health-care research and policies, reflecting the trends and developments in the use of survey instruments on population health., ((c) 2020 The authors; licensee World Health Organization.)

Introduction: Although the use of Reference Management Software (RMS) is increasing in developed countries, they seem to be unknown and less used in low-income countries., Aim: To discover the major trends in the use of RMS among researchers and Ph.D. students in Tunisia, as a low-income country., Methods: A hardcopy survey was filled out by researchers and Ph.D. students during an educational seminar at the faculty of medicine of Sfax in 2016 with the aim to collect qualitative data to determine the participants' knowledge and use of RMS., Results: The survey collected 121 participants, among them, 53.7% know RMS. Mendeley proved to be the best-known software (41.5%), followed by Zotero (35.3%) and Endnote (23%). Training sessions in RMS were taken by 5% of participants. Among the 121 participants, 26.5%of them use RMS., Mendeley was the most used (46.9%), followed by EndNote (28.1%) and Zotero (25%). The most commonly popular feature in RMS is inserting citations (66.9%). Therefore, the analysis, of the reasons behind the choice of RMS proves that the software was used because it is convenient (38.4%),  most known (38.4%),  easy (30.7%), or suggested by colleagues (30.7%). The free and open-source software was preferred by 81% of the participants. g. However, 50.4% ignore the fact that Zotero is free. Several types and sources of captured citations were unknown by 53.8% and 59% of the rest of the participants., Conclusion: The results clearly show that the lack of awareness about RMS in Tunisia is due to the absence of a formal training. As a result, the need for such training is highly important for researchers to be able to benefit from the different advantages of RMS while conducting their academic medical education.

Objective: Pharmaceuticals play an important role in clinical care. However, in community-based research, medication data are commonly collected as unstructured free-text, which is prohibitively expensive to code for large-scale studies. The ASPirin in Reducing Events in the Elderly (ASPREE) study developed a two-pronged framework to collect structured medication data for 19,114 individuals. ASPREE provides an opportunity to determine whether medication data can be cost-effectively collected and coded, en masse from the community using this framework., Methods: The ASPREE framework of type-to-search box with automated coding and linked free text entry was compared to traditional method of free-text only collection and post hoc coding. Reported medications were classified according to their method of collection and analysed by Anatomical Therapeutic Chemical (ATC) group. Relative cost of collecting medications was determined by calculating the time required for database set up and medication coding., Results: Overall, 122,910 participant structured medication reports were entered using the type-to-search box and 5,983 were entered as free-text. Free-text data contributed 211 unique medications not present in the type-to-search box. Spelling errors and unnecessary provision of additional information were among the top reasons why medications were reported as free-text. The cost per medication using the ASPREE method was approximately USD $0.03 compared with USD $0.20 per medication for the traditional method., Conclusion: Implementation of this two-pronged framework is a cost-effective alternative to free-text only data collection in community-based research. Higher initial set-up costs of this combined method are justified by long term cost effectiveness and the scientific potential for analysis and discovery gained through collection of detailed, structured medication data., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: Breast cancer is the second leading cause of cancer death worldwide. The economic burden of breast cancer is crucial for the sustainability of healthcare systems. The objective of this study was to estimate the burden of HR+/HER2- metastatic breast cancer (MBC) in Italy, in terms of incidence, prescription patterns, healthcare resource utilisation and costs for the National Health System (NHS)., Methods: A cohort study based on healthcare administrative data (ReS database), covering > 10 million Italians, was performed. Incident cases of HR+/HER2- MBC were identified among adult women in 2013. The cohort was followed-up for 2 years to describe healthcare utilisation and integrated costs (pharmaceuticals, hospitalisations and outpatient services) for NHS. Prescription patterns were described as first-line choice and therapeutic changes. Specific therapeutic changes were used as proxies of disease progression. A survival analysis was performed to estimate the time from diagnosis to first disease progression., Results: Of 5174,723 women, 355 cases of de novo HR+/HER2- MBC were selected (incidence: 6.9 per 100,000). During the 1st follow-up year, they generated an average cost of €7543, whereas €4834 in the 2nd year. The 85.9% received a monotherapy, while the 14.1% received a combination therapy. The most used monotherapy was nonsteroidal-aromatase-inhibitors (45.9%), while the most prescribed combination was tamoxifen + luteinizing hormone releasing hormone (LHRH) analogues (6.2%). Therapeutic changes occurred in 45.4% of patients, especially from chemotherapy to nonsteroidal-aromatase-inhibitors, after an average of 276.8 days from the first treatment. Disease progression was identified in 22.5% of patients occurring after a mean 13 ± 6 months from diagnosis., Conclusions: This detailed picture of HR+/HER2- MBC, based on real-world data, could be helpful in health technology assessment and expenditure forecasts of future therapeutic strategies for this condition in Italy.

Background: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in nondiabetic adults. Approximately one third of patients with MN progress to end-stage renal disease (ESRD), while others may be successfully treated to remission. Patients with MN represent a high-risk population for whom management strategies can alter and improve outcomes. Currently, there is little real-world evidence regarding the burden of MN on health plans., Objectives: To (a) characterize clinical and economic outcomes during a 1-year time frame among a prevalent cohort of patients with MN and (b) compare the 5% of patients incurring the highest cost with the remaining 95%., Methods: A retrospective analysis of commercially insured patients was conducted using MarketScan administrative health care claims data from January 1, 2012, to December 31, 2015. Patients were aged ≥ 18 years, enrolled In a fee-for-service plan, and had ≥ 2 medical claims for an MN diagnosis (ICD-9-CM codes 581.1, 582.1, and 583.1). Diagnoses indicating clear secondary causes were excluded wherever possible. Demographics were determined as of the first diagnosis date; clinical characteristics (e.g., MN-specific therapy, complications, and procedures), health care resource utilization (HCRU; inpatient, outpatient including other outpatient and emergency department [ED], and prescriptions), and costs were evaluated for 1 year following MN diagnosis. Total costs and cost distribution (2017 U.S. dollars) were examined using plan-paid and patient-paid amounts. The 95th percentile was used to categorize and compare the subcohorts: high-cost cohort (HCC) patients (top 5%) and non-high-cost cohort (NHCC) patients (the remaining 95%). Descriptive analyses, chi-square tests, and Wilcoxon rank-sum tests were conducted., Results: 2,689 patients were identified (60.0% male, mean age = 46.4 years). Severity and advanced disease were observed In a higher proportion of HCC patients (n = 134) versus NHC patients (n = 2,555) via adverse health outcomes, procedures, and immunosuppressant use. HCC patients used significantly more resources on average than NHCC patients (additional use): 1.7 inpatient, 1.2 ED, and 4.8 outpatient office visits; 15 prescriptions; and 64.8 other outpatient visits (i.e., outpatient, hospital, and ESRD facilities). Total MN-related cost and mean (SD) cost per patient were $123.2 million and $45,814 ($101,353); HCC patients accounted for 43.7% of total costs for a mean cost per patient of $401,608 versus NHCC patients at 56.3% and mean cost per patient of $27,154. The greatest costs for both groups were related to outpatient visits (HCC = 46.7%; NHCC = 52.8%), inpatient visits (HCC = 27.7%; NHCC = 28.6%), and prescriptions (HCC = 25.7%; NHCC = 18.6%)., Conclusions: Patients with MN are significantly burdened with high disease severity and adverse health outcomes, resulting In substantial HCRU and costs. Health plan cost drivers for MN (HCC and NHCC patients) occurred primarily In the outpatient setting, followed by the inpatient setting and prescriptions. Modifiable aspects preceding progression to advanced renal disease and worse outcomes should be explored to Identify effective interventions and improve resource allocation earlier In the disease pathway, before ESRD., Disclosures: This study was funded by Mallinckrodt Pharmaceuticals. Kirkemo, Pavlova-Wolf, and Bartels-Peculis are employees and stockholders of Mallinckrodt Pharmaceuticals. Nazareth was an employee of Mallinckrodt Pharmaceuticals at the time of this study. Kariburyo, Xie, and Vaidya are employees of STATinMED Research, a paid consultant to Mallinckrodt Pharmaceuticals. Sim received an investigator-initiated research grant from Mallinkcrodt Pharmaceuticals. A portion of the study results were previously presented at the American Society of Nephrology (ASN) Kidney Week 2017; November 2, 2017; New Orleans, LA.

Study Design: Retrospective, observational study., Objective: To examine the costs associated with nonoperative management (diagnosis and treatment) of cervical radiculopathy in the year prior to anterior cervical discectomy and fusion (ACDF)., Summary of Background Data: While the costs of operative treatment have been previously described, less is known about nonoperative management costs of cervical radiculopathy leading up to surgery., Methods: The Humana claims dataset (2007-2015) was queried to identify adult patients with cervical radiculopathy that underwent ACDF. Outcome endpoint was assessment of cumulative and per-capita costs for nonoperative diagnostic (x-rays, computed tomographic [CT], magnetic resonance imaging [MRI], electromyogram/nerve conduction studies [EMG/NCS]) and treatment modalities (injections, physical therapy [PT], braces, medications, chiropractic services) in the year preceding surgical intervention., Results: Overall 12,514 patients (52% female) with cervical radiculopathy underwent ACDF. Cumulative costs and per-capita costs for nonoperative management, during the year prior to ACDF was $14.3 million and $1143, respectively. All patients underwent at least one diagnostic test (MRI: 86.7%; x-ray: 57.5%; CT: 35.2%) while 73.3% patients received a nonoperative treatment. Diagnostic testing comprised of over 62% of total nonoperative costs ($8.9 million) with MRI constituting the highest total relative spend ($5.3 million; per-capita: $489) followed by CT ($2.6 million; per-capita: $606), x-rays ($0.54 million; per-capita: $76), and EMG/NCS ($0.39 million; per-capita: $467). Conservative treatments comprised of 37.7% of the total nonoperative costs ($5.4 million) with injections costs constituting the highest relative spend ($3.01 million; per-capita: $988) followed by PT ($1.13 million; per-capita: $510) and medications (narcotics: $0.51 million, per-capita $101; gabapentin: $0.21 million, per-capita $93; NSAIDs: 0.107 million, per-capita $47), bracing ($0.25 million; per-capita: $193), and chiropractic services ($0.137 million; per-capita: $193)., Conclusion: The study quantifies the cumulative and per-capital costs incurred 1-year prior to ACDF in patients with cervical radiculopathy for nonoperative diagnostic and treatment modalities. Approximately two-thirds of the costs associated with cervical radiculopathy are from diagnostic modalities. As institutions begin entering into bundled payments for cervical spine disease, understanding condition specific costs is a critical first step., Level of Evidence: 3.

Background: Kidney transplant (KT) patients presenting with cardiovascular (CVD) events are being managed increasingly in non-transplant facilities. We aimed to identify drivers of mortality and costs, including transplant hospital status., Methods: Data from the 2009-2011 Nationwide Inpatient Sample, the American Hospital Association, and Hospital Compare were used to evaluate post-KT patients hospitalized for MI, CHF, stroke, cardiac arrest, dysrhythmia, and malignant hypertension. We used generalized estimating equations to identify clinical, structural, and process factors associated with risk-adjusted mortality and high cost hospitalization (HCH)., Results: Data on 7803 admissions were abstracted from 275 hospitals. Transplant hospitals had lower crude mortality (3.0% vs. 3.8%, p = 0.06), and higher un-adjusted total episodic costs (Median $33,271 vs. $28,022, p < 0.0001). After risk-adjusting for clinical, structural, and process factors, mortality predictors included: age, CVD burden, CV destination hospital, diagnostic cardiac catheterization without intervention (all, p < 0.001). Female sex, race, documented co-morbidities, and hospital teaching status were protective (all, p < 0.05). Transplant and non-transplant hospitals had similar risk-adjusted mortality. HCH was associated with: age, CVD burden, CV procedures, and staffing patterns. Hospitalizations at transplant facilities had 37% lower risk-adjusted odds of HCH. Cardiovascular process measures were not associated with adverse outcomes., Conclusion: KT patients presenting with CVD events had similar risk-adjusted mortality at transplant and non-transplant hospitals, but high cost care was less likely in transplant hospitals. Transplant hospitals may provide better value in cardiovascular care for transplant patients. These data have significant implications for patients, transplant and non-transplant providers, and payers.

In July 2018, the National Guideline Clearinghouse lost funding, leaving fewer freely available online guideline collections. Based on the authors' experience of the 3 major guideline-focused databases that are currently available (Guidelines International Network, the Turning Research into Practice database, and Guideline Central) an easy to use resource with stringent inclusion criteria is currently lacking, though new resources are in development. These 3 resources vary in scope, and none stood out as an all-encompassing favorite. Regardless of the source used to find and access guidelines, clinicians must evaluate guideline quality and currency before using them in clinical practice.

Objectives: Surgical site infections (SSIs) result in significant negative clinical and economic outcomes. The objective of this study is to estimate annual health expenditures associated with spinal cord stimulation (SCS)-related infections., Materials and Methods: Data from the Truven MarketScan® databases were used to identify patients with an SCS implant (2009-2014) and a continuous health plan enrollment for at least 12-months before and after implant (index date). Annual expenditures were estimated for patients with a device-related infection vs. those without infection since index date. A generalized linear model estimated annual expenditures attributable to device-related infection. Multivariable expenditure models were conducted separately for patients in initial and replacement groups, controlling for demographics, comorbidities, and clinical characteristics., Results: The study included 6615 patients. Multivariable expenditure models revealed that patients with infection have higher annual expenditures than patients without infection. Estimated incremental annual healthcare expenditures for patients with an infection were $59,716 (95% CI: $48,965-$69,480) for initial implanted patients and $64,833 (95% CI: $37,377-$86,519) for replacement patients. Only 26% of patients who were explanted for infection underwent a reimplant., Conclusions: These results show the substantial expenditure burden associated with an SCS-related infection. Management of SCS-related infection is important from both clinical and economic standpoints. The economic and clinical data presented here reinforce the need for additional research and strategies for healthcare providers to minimize SCS infections. Future economic research is needed to further define the specific economic cost drivers associated with the extensive expenditure burden., (© 2019 International Neuromodulation Society.)

Background: Phenylketonuria is a well-known rare disease included in the neonatal screening of many countries. Therefore, there are few published data on the admissions and costs of phenylketonuria in Spain., Objective: The objective of this study was to assess the number of admissions and the economic burden of phenylketonuria in Spain., Methods: Patients with phenylketonuria were identified from a Spanish database containing data from public and private healthcare centres from 1997 to 2015. The parameters obtained were characteristics of the patients, type of admissions, readmissions, discharges, length of stay, medical service, annual number of visits, annual number of patients, visit-associated costs and patient-associated costs., Results: Five hundred and ninety-four patients with phenylketonuria were identified: 48.32% were male with a mean (standard deviation) age of 4.50 (10.23) years. The hospital admissions were divided into emergency visits (55.94%) and scheduled visits (43.92%). The majority of patients were discharged home (98.86%). The mean (standard deviation) duration of stay was 4.04 (4.98) days. The number of admissions per year ranged between 13 and 88, with an average of 1.18 admissions per patient per year. Finally, the mean cost per visit increased from €1064.91 to €3709.40, and the mean cost per patient increased from €1818.90 to €4239.32 from 1999 to 2015., Conclusions: The access to economic and social data on phenylketonuria in Spain has been updated. The number of admissions in Spain between 1997 and 2015 and healthcare costs between 1999 and 2015 were calculated. There were 24 admissions as a result of a phenylketonuria diagnosis in 2015 and the mean healthcare cost per patient was €4239.32. This information can help to adapt and improve each healthcare system to take into consideration rare diseases.

Emerging health care research paradigms such as comparative effectiveness research (CER), patient-centered outcome research (PCOR), and precision medicine (PM) share one ultimate goal: constructing evidence to provide the right treatment to the right patient at the right time. We argue that to succeed at this goal, it is crucial to have both timely access to individual-level data and fine geographic granularity in the data. Existing data will continue to be an important resource for observational studies as new data sources are developed. We examined widely used publicly funded health databases and population-based survey systems and found four ways they could be improved to better support the new research paradigms: (1) finer and more consistent geographic granularity, (2) more complete geographic coverage of the US population, (3) shorter time from data collection to data release, and (4) improved environments for restricted data access. We believe that existing data sources, if utilized optimally, and newly developed data infrastructures will both play a key role in expanding our insight into what treatments, at what time, work for each patient.

Background: Despite increasing usage of endovascular treatments for intracranial aneurysms, few research studies have been conducted on the incidence of unruptured aneurysm (UA) and subarachnoid hemorrhage (SAH), and could not show a decrease in the incidence of SAH. Moreover, research on socioeconomic disparities with respect to the diagnosis and treatment of UA and SAH is lacking., Method: Trends in the incidences of newly detected UA and SAH and trends in the treatment modalities used were assessed from 2005 to 2015 using the nationwide database of the Korean National Health Insurance Service in South Korea. We also evaluated the influence of demographic characteristics including socioeconomic factors on the incidence and treatment of UA and SAH., Result: The rates of newly detected UA and SAH were 28.3 and 13.7 per 100 000 of the general population, respectively, in 2015. The incidence of UA increased markedly over the 11-year study period, whereas that of SAH decreased slightly. UA patients were more likely to be female, older, employee-insured, and to have high incomes than SAH patients. In 2015, coiling was the most common treatment modality for both UA and SAH patients. Those who were female, employee-insured, or self-employed, with high income were likely to have a higher probability to be treated for UA and SAH., Conclusion: The marked increase in the detection and treatment of UA might have contributed to the decreasing incidence of SAH, though levels of contribution depend on socioeconomic status despite universal medical insurance coverage., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: There is currently a paucity of literature evaluating procedural reimbursements and financial trends in neurosurgery. A comprehensive understanding of the economic trends and financial health of neurosurgery is important to ensure the sustained success and growth of the specialty moving forward. The purpose of this study was to evaluate monetary trends of the 10 most common spinal and cranial neurosurgical procedures in Medicare reimbursement rates from 2000 to 2018., Methods: The Physician Fee Schedule Look-Up Tool from the Centers for Medicare & Medicaid Services was queried for each of the top 10 most utilized Current Procedural Terminology codes in both spinal and cranial neurosurgery, and comprehensive reimbursement data were extracted. The raw percent change in Medicare reimbursement rate from 2000 to 2018 was calculated for each procedure and averaged. This was then compared to the percent change in consumer price index over the same time. Using data adjusted for inflation, trend analysis was performed for all included procedures. Adjusted R-squared and both the average annual and the total percent change in reimbursement were calculated based on these adjusted trends for all included procedures. Likewise, the compound annual growth rate was calculated for all procedures., Results: When all reimbursement data were adjusted for inflation, the average reimbursement for all procedures decreased by an average of 25.80% from 2000 to 2018. From 2000 to 2018, the adjusted reimbursement rate for all included procedures decreased by an average of 1.59% each year and experienced an average compound annual growth rate of -1.66%, indicating a steady annual decline in reimbursement when adjusted for inflation., Conclusions: This is the first study to evaluate comprehensive trends in Medicare reimbursement in neurosurgery. When adjusted for inflation, Medicare reimbursement for all included procedures has steadily decreased from 2000 to 2018, with similar rates of decline observed between cranial and spinal neurosurgery procedures. Increased awareness and consideration of these trends will be important moving forward for policy makers, hospitals, and neurosurgeons as continued progress is made to advance agreeable reimbursement models that allow for the sustained growth of neurosurgery in the United States.

Background: Merging United Network for Organ Sharing (UNOS) and Pediatric Health Information Systems databases has enabled a more granular analysis of pediatric heart transplant outcomes and resource utilization. We evaluated whether transplant indication at time of transplantation was associated with mortality, resource utilization, and inpatient costs during the first year after transplantation., Methods and Results: We analyzed transplant outcomes and resource utilization from 2004 to 2015. Patients were categorized as congenital (CHD), myocarditis, or cardiomyopathy based on UNOS-defined primary indication. CHD complexity subgroup analyses (single-ventricle, complex, and simple biventricular CHD) were also performed. Of 2251 transplants (49% CHD, 5% myocarditis, 46% cardiomyopathy), CHD recipients were younger (2 [IQR 0-10], 6 [IQR 0-12], and 7 [IQR 1-14] years, respectively; P < .001) and less likely to have a ventricular assist device (VAD) at transplantation (3%, 27%, and 13%, respectively; P < .001). Patients with single-ventricle CHD had the longest time on the waitlist and were least likely to receive a VAD before transplantation. After adjusting for patient-level factors, transplant recipients with single-ventricle CHD had the greatest mortality during transplantation admission and within 1 year (odds ratio [OR] 11.8 [95% confidence interval (CI) 5.9-23.6] and OR 6.0 [95% CI 3.6-10.2], respectively, vs cardiomyopathy). Mortality was similar between patients with myocarditis and cardiomyopathy. Post-transplantation length of stay (LOS) was longer in transplant recipients with CHD than myocarditis or cardiomyopathy (25 [interquartile range [IQR] 15-45] vs 21 [IQR 12-35] vs 16 [IQR 12-25] days; P < .001), related in part to longer duration of intensive care unit-level care (ICU LOS 8 [IQR 4-20] vs 6 [IQR 4-13] vs 5 [IQR 3-8] days; P < .001). Similarly, patients with CHD had higher median post-transplantation costs than myocarditis or cardiomyopathy ($415K [IQR $201K-503K] vs $354K [IQR $179K-390K] vs $284K [IQR $145K-319K]; P < .001) that persisted after adjusting for patient-level factors (adjusted cost ratio 1.4 [95% CI 1.4-1.5], CHD vs cardiomyopathy) and was primarily driven by longer LOS. More than 50% were readmitted during the first year after transplantation, although readmission rates were similar across transplant indications (P = .42)., Conclusions: Children with CHD, particularly single-ventricle patients, require substantially greater hospital resource utilization and have significantly worse outcomes during the first year after heart transplantation compared with other indications. Further work is aimed at identifying modifiable pre-transplantation risk factors, such as pre-transplantation conditioning with VAD support and cardiac rehabilitation, to improve post-transplantation outcomes and reduce resource utilization in this complex population., (Copyright © 2018. Published by Elsevier Inc.)

Background and Objectives: A new oral antidiabetic drug class, sodium-glucose co-transporter-2 inhibitors (SGLT-2 inhibitors), has been covered by national health insurance in Taiwan since May 2016. This study estimated the impacts of insurance coverage for SGLT-2 inhibitors on the replacement effects of antidiabetic drug use and the overall budget for antidiabetic drugs in Taiwan., Methods: Antidiabetic drugs were divided into nine categories based on the American Diabetes Association guidelines. We retrieved claims data from 2015 to 2017 for all patients diagnosed with diabetes mellitus from the National Health Insurance Research Database. An interrupted time series design and segmented regression were used to estimate the budget impact of insurance coverage for SGLT-2 inhibitors. Three scenarios were designed for the prescribing pattern for SGLT-2 inhibitors: (1) monotherapy, (2) metformin-based (m-based) drug prescriptions, and (3) metformin and sulfonylurea-based (m-s-based) drug prescriptions., Results: From May 2016 to April 2017, the prescription rate for m-based SGLT-2 inhibitors increased from 0.43 to 3.50%, and the expenditure rate increased from 0.82 to 6.58%. We found that the prescription rates of m-based and m-s-based dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) decreased by 6.23 and 11.51% following the initiation of insurance coverage for SGLT-2 inhibitors, respectively. Furthermore, there was a 5.95% increase in the overall budget impact of antidiabetic drugs 1 year following the initiation of insurance coverage for SGLT-2 inhibitors., Conclusions: Both the prescription rates and expenditure rates for SGLT-2 inhibitors have increased since they have been covered by national health insurance in Taiwan, which significantly reduced usage of DPP-4 inhibitors but caused the positive growth of overall antidiabetic drug expenditures.

Background: The financial relationship between physicians and industries has become a hotly debated issue globally. The Physician Payments Sunshine Act of the US Affordable Care Act (2010) promoted transparency of the transactions between industries and physicians by making remuneration data publicly accessible in the Open Payments Program database. Meanwhile, according to the World Health Organization, the majority of all noncommunicable disease deaths were caused by cardiovascular disease., Objective: This study aimed to investigate the distribution of non-research and non-ownership payments made to thoracic surgeons, to explore the regularity of financial relationships between industries and thoracic surgeons., Methods: Annual statistical data were obtained from the Open Payments Program general payment dataset from 2014-2016. We characterized the distribution of annual payments with single payment transactions greater than US $10,000, quantified the major expense categories (eg, Compensation, Consulting Fees, Travel and Lodging), and identified the 30 highest-paying industries. Moreover, we drew out the financial relations between industries to thoracic surgeons using chord diagram visualization., Results: The three highest categories with single payments greater than US $10,000 were Royalty or License, Compensation, and Consulting Fees. Payments related to Royalty or License transferred from only 5.38% of industries to 0.75% of surgeons with the highest median (US $13,753, $11,992, and $10,614 respectively) in 3-year period. In contrast, payments related to Food and Beverage transferred from 93.50% of industries to 98.48% of surgeons with the lowest median (US $28, $27, and $27). The top 30 highest-paying industries made up approximately 90% of the total payments (US $21,036,972, $23,304,996, and $28,116,336). Furthermore, just under 9% of surgeons received approximately 80% of the total payments in each of the 3 years. Specifically, the 100 highest cumulative payments, accounting for 52.69% of the total, transferred from 27 (6.05%) pharmaceutical industries to 86 (1.89%) thoracic surgeons from 2014-2016; 7 surgeons received payments greater than US $1,000,000; 12 surgeons received payments greater than US $400,000. The majority (90%) of these surgeons received tremendous value from only one industry., Conclusions: There exists a great discrepancy in the distribution of payments by categories. Royalty or License Fees, Compensation, and Consulting Fees are the primary transferring channels of single large payments. The massive transfer from industries to surgeons has a strong "apical dominance" and excludability. Further research should focus on discovering the fundamental driving factors for the strong concentration of certain medical devices and how these payments will affect the industry itself., (©Xu Na, Haihong Guo, Yu Zhang, Liu Shen, Sizhu Wu, Jiao Li. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 30.11.2018.)

Introduction: A study in 2011 by (Doody et al. Ir Med J 106(10):300-302, 2013) looked at comparing inpatient adverse events recorded prospectively at the point of care, with adverse events recorded by the national Hospital In-Patient Enquiry (HIPE) System., Methods: In the study, a single-centre University Hospital in Ireland treating acute hip fractures in an orthopaedic unit recorded 39 patients over a 2-month (August-September 2011) period, with 55 adverse events recorded prospectively in contrast to the HIPE record of 13 (23.6%) adverse events. With the recent change in the Irish hospital funding model from block grant to an 'activity-based funding' on the basis of case load and case complexity, the hospital financial allocation is dependent on accurate case complexity coding. A retrospective assessment of the financial implications of the two methods of adverse incident recording was carried out., Results: A total of €39,899 in 'missed funding' for 2 months was calculated when the ward-based, prospectively collected data was compared to the national HIPE data. Accurate data collection is paramount in facilitating activity-based funding, to improve patient care and ensure the appropriate allocation of resources.

Background: The objective of this study was to examine patient characteristics and health care resource utilization (HCRU) in the 36 months prior to a confirmatory diagnosis of Alzheimer's disease (AD) compared to a matched cohort without dementia during the same time interval., Methods: Patients newly diagnosed with AD (with ≥2 claims) were identified between January 1, 2013 to September 31, 2015, and the date of the second claim for AD was defined as the index date. Patients were enrolled for at least 36 months prior to index date. The AD cohort was matched to a cohort with no AD or dementia codes (1:3) on age, gender, race/ethnicity, and enrollment duration prior to the index date. Descriptive analyses were used to summarize patient characteristics, HCRU, and healthcare costs prior to the confirmatory AD diagnosis. The classification and regression tree analysis and logistic regression were used to identify factors associated with the AD diagnosis., Results: The AD cohort (N = 16,494) had significantly higher comorbidity indices and greater odds of comorbid mental and behavioral diagnoses, including mild cognitive impairment, mood and anxiety disorders, behavioral disturbances, and cerebrovascular disease, heart disease, urinary tract infections, and pneumonia than the matched non-AD or dementia cohort (N = 49,482). During the six-month period before the confirmatory AD diagnosis, AD medication use and diagnosis of mild cognitive impairment, Parkinson's disease, or mood disorder were the strongest predictors of a subsequent confirmatory diagnosis of AD. Greater HCRU and healthcare costs were observed for the AD cohort primarily during the six-month period before the confirmatory AD diagnosis., Conclusion: The results of this study demonstrated a higher comorbidity burden and higher costs for patients prior to a diagnosis of AD in comparison to the matched cohort. Several comorbidities were associated with a subsequent diagnosis of AD.

Objectives: To describe all published articles that have conducted comparisons of model-based effectiveness and cost-effectiveness results in the field of vaccination. Specific objectives were to 1) describe the methodologies used and 2) identify the strengths and limitations of the studies., Methods: We systematically searched MEDLINE and Embase databases for studies that compared predictions of effectiveness and cost-effectiveness of vaccination of two or more mathematical models. We categorized studies into two groups on the basis of their data source for comparison (previously published results or new simulation results) and performed a qualitative synthesis of study conclusions., Results: We identified 115 eligible articles (only 5% generated new simulations from the reviewed models) examining the effectiveness and cost-effectiveness of vaccination against 14 pathogens (69% of studies examined human papillomavirus, influenza, and/or pneumococcal vaccines). The goal of most of studies was to summarize evidence for vaccination policy decisions, and cost-effectiveness was the most frequent outcome examined. Only 33%, 25%, and 3% of studies followed a systematic approach to identify eligible studies, assessed the quality of studies, and performed a quantitative synthesis of results, respectively. A greater proportion of model comparisons using published studies followed a systematic approach to identify eligible studies and to assess their quality, whereas more studies using new simulations performed quantitative synthesis of results and identified drivers of model conclusions. Most comparative modeling studies concluded that vaccination was cost-effective., Conclusions: Given the variability in methods used to conduct/report comparative modeling studies, guidelines are required to enhance their quality and transparency and to provide better tools for decision making., (Copyright © 2018 ISPOR--The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: Efficient allocation of resources in the healthcare system enables providers to care for more and needier patients. Identifying drivers of total charges for transsphenoidal surgery (TSS) for pituitary tumors, which are poorly understood, represents an opportunity for neurosurgeons to reduce waste and provide higher-quality care for their patients. In this study the authors used a large, national database to build machine learning (ML) ensembles that directly predict total charges in this patient population. They then interrogated the ensembles to identify variables that predict high charges., Methods: The authors created a training data set of 15,487 patients who underwent TSS between 2002 and 2011 and were registered in the National Inpatient Sample. Thirty-two ML algorithms were trained to predict total charges from 71 collected variables, and the most predictive algorithms combined to form an ensemble model. The model was internally and externally validated to demonstrate generalizability. Permutation importance and partial dependence analyses were performed to identify the strongest drivers of total charges. Given the overwhelming influence of length of stay (LOS), a second ensemble excluding LOS as a predictor was built to identify additional drivers of total charges., Results: An ensemble model comprising 3 gradient boosted tree classifiers best predicted total charges (root mean square logarithmic error = 0.446; 95% CI 0.439-0.453; holdout = 0.455). LOS was by far the strongest predictor of total charges, increasing total predicted charges by approximately $5000 per day.In the absence of LOS, the strongest predictors of total charges were admission type, hospital region, race, any postoperative complication, and hospital ownership type., Conclusions: ML ensembles predict total charges for TSS with good fidelity. The authors identified extended LOS, nonelective admission type, non-Southern hospital region, minority race, postoperative complication, and private investor hospital ownership as drivers of total charges and potential targets for cost-lowering interventions.

Background: To assess whether implementation of the Mental Health Parity and Addiction Equity Act (MHPAEA) was associated with: 1. Reduced differences in financial requirements (i.e., copayments and coinsurance) for substance use disorder (SUD) versus specialty mental health (MH) care and 2. Reductions in the level of cost-sharing for SUD-specific services., Methods: MH and SUD copayments and coinsurance, 2008-2013, were obtained from benefits databases for carve-in and carve-out plans from Optum ® . Linear regression was used to estimate the association of MHPAEA with differences between MH and SUD care financial requirements among carve-in and carve-out plans. A two-part regression model investigated whether MHPAEA was associated with changes in the use or level of financial requirements for SUD-specific services among carve-out plans., Results: MHPAEA was not associated with significant changes in the difference between SUD and MH copayments or coinsurance levels among either carve-in or carve-out plans. MHPAEA was associated with decreases in the levels of inpatient (in-network: -$51.17; out-of-network: -$34.39) and outpatient (in-network: -$10.26) detox copayments, but increases in the levels of in-network outpatient detox coinsurance (6 percentage points) among all carve-out plans., Conclusion: Even if SUD benefits had been historically less generous than MH benefits, SUD financial requirements were already at parity with MH financial requirements by the time MHPAEA was passed, among Optum ® plans. MHPAEA's SUD parity mandate reduced cost-sharing for detox services via copayments, but, for outpatient detox, the law simultaneously increased cost-sharing via coinsurance., (Copyright © 2018. Published by Elsevier B.V.)

Research information is useful only if it can be shared-with other researchers, with research organizations (institutions, laboratories, funders and others), and with the wider community. In our digital age, that means sharing information between data systems. Persistent identifiers (PIDs) provide unique keys for people, places and things, which enables accurate mapping of information between these systems and supports the research process by facilitating search, discovery, recognition and collaboration. This article reviews the main PIDs used in research-digital object identifiers for publications, ORCID iDs for researchers, and a proposed new identifier for research organizations-as well as demonstrating how they are being used, and how, in combination, they can increase trust in research and the research infrastructure.

Background and Objectives: Thirty million children are currently covered by public insurance; however, the future funding and structure of public insurance are uncertain. Our objective was to determine the number, estimated costs, and demographic characteristics of hospitalizations that would become ineligible for public insurance reimbursement under 3 federal poverty level (FPL) eligibility scenarios., Methods: In this retrospective cohort study using the 2014 State Inpatient Databases, we included all pediatric (age <18) hospitalizations in 14 states from January 1, 2014, to December 31, 2014, with public insurance as the primary payer. We linked each patient's zip code to the American Community Survey to determine the likelihood of the patient being below 3 different public insurance income eligibility thresholds (300%, 200%, and 100% of the FPL). Multiple simulations were used to describe newly ineligible hospitalizations under each threshold., Results: In 775 460 publicly reimbursed hospitalizations in 14 states, reductions in eligibility limits to 300%, 200%, or 100% of the FPL would have resulted in large numbers of newly ineligible hospitalizations (∼155 000 [20% of hospitalizations] for 300%, 440 000 [57%] for 200%, and 650 000 [84%] for 100% of the FPL), equaling $1.2, $3.1, and $4.4 billion of estimated child hospitalization costs, respectively. Patient demographics differed only slightly under each eligibility threshold., Conclusions: Reducing public insurance eligibility limits would have resulted in numerous pediatric hospitalizations not covered by public insurance, shifting costs to families, other insurers, or hospitals. Without adequately subsidized commercial insurance, this reflects a potentially substantial economic hardship for families and hospitals serving them., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)