Large Clinical Database Research Articles

Sonic Hedgehog, a Novel Endogenous Damage Signal, Activates Multiple Beneficial Functions of Human Endometrial Stem Cells.

Local endometrial stem cells play an important role in regulating endometrial thickness, which is an essential factor for successful embryo implantation and pregnancy outcomes. Importantly, defects in endometrial stem cell function can be responsible for thin endometrium and subsequent recurrent pregnancy losses. Therefore, many researchers have directed their efforts toward finding a novel stimulatory factor that can enhance the regenerative capacity of endometrial stem cells. Sonic hedgehog (SHH) is a morphogen that plays a key role in regulating pattern formation throughout embryonic limb development. In addition to this canonical function, we identified for the first time that SHH is actively secreted as a stem cell-activating factor in response to tissue injury and subsequently stimulates tissue regeneration by promoting various beneficial functions of endometrial stem cells. Our results also showed that SHH exerts stimulatory effects on endometrial stem cells via the FAK/ERK1/2 and/or phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. More importantly, we also observed that endometrial stem cells stimulated with SHH showed markedly enhanced differentiation and migratory capacities and subsequent invivo therapeutic effects in an endometrial ablation animal model.

A Machine Learning Approach for Studying the Comorbidities of Complex Diagnoses.

The study of diagnostic associations entails a large number of methodological problems regarding the application of machine learning algorithms, collinearity and wide variability being some of the most prominent ones. To overcome these, we propose and tested the usage of uniform manifold approximation and projection (UMAP), a very recent, popular dimensionality reduction technique. We showed its effectiveness by using it on a large Spanish clinical database of patients diagnosed with depression, to whom we applied UMAP before grouping them using a hierarchical agglomerative cluster analysis. By extensively studying its behavior and results, validating them with purely unsupervised metrics, we show that they are consistent with well-known relationships, which validates the applicability of UMAP to advance the study of comorbidities.

Effect of Body Mass Index on Outcomes After Surgery for Perforated Diverticulitis

BackgroundDespite the increased adoption of minimally invasive techniques in colorectal surgery, an open resection with ostomy creation remains an accepted operation for perforated diverticulitis. In the United States, there is an increase in the rates of both morbid obesity and diverticular disease. Therefore, we wanted to explore whether outcomes for morbidly obese patients with diverticulitis are worse than nonmorbidly obese patients after open colectomy for diverticulitis. Materials and methodsUsing the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2015, we identified adults with emergent admission for diverticulitis (International Classification of Diseases, Ninth Revision, code 562.11) with evidence of preoperative sepsis and intraoperative contaminated/dirty wound classification, in which a resection with ostomy (Current Procedural Terminology codes 44141, 44143, or 44144) was performed. We excluded cases with age >90 y, ventilator dependence, evidence of disseminated cancer and missing sex, race, body mass index, functional status, American Society of Anesthesiologists class, length of stay (LOS), or operative time data. Morbid obesity was defined as body mass index >35 kg/m2. Risk variables of interest included age, sex, race, medical comorbidities, requirement for preoperative transfusion, preoperative sepsis, and operative time. Outcomes of interest included LOS, 30-d postoperative complications, and mortality. Univariate and propensity scores with postmatching analyses were performed. ResultsA total of 2019 patients met inclusion and exclusion criteria, of which 413 (20.5%) were morbidly obese. Morbidly obese patients tended to be younger (mean 57.2 versus 62.6 y) and female (54.5% versus 45.5%). Morbidly obese patients also had higher rates of insulin-dependent diabetes (8.0% versus 4.2%), hypertension (60.1% versus 51.3%), renal failure (3.4% versus 1.5%), and higher American Society of Anesthesiologists class (class 4: 23.5% versus 19.6% and class 5: 1.45% versus 0.87%). Morbidly obese patient had no increase in 30-d mortality or LOS, but they had higher rates of superficial wound infection (9.0% versus 5.8%; P = 0.0259), deep wound infection (4.4% versus 1.9%; P = 0.0073), acute renal failure (4.8% versus 2.4%; P = 0.0189), postoperative septic shock (17.7% versus 12.1%; P = 0.0040), and return to the operating room (11.1% versus 6.4%; P = 0.0015). We identified 397 morbidly obese patients well matched by propensity score to 397 nonmorbidly obese patients. Conditional logistic regression showed no difference in LOS (median 12.9 versus 12.4 d; P = 0.4648) and no increased risk of 30-d mortality (P = 0.947), but morbid obesity was an independent predictor for return to the operating room (adjusted odds ratio: 27.09 [95% confidence interval: 2.68-274.20]; P = 0.005). ConclusionsThis analysis of a large national clinical database demonstrates that morbidly obese patients presenting with perforated diverticulitis undergoing a Hartmann's procedure do not have increased mortality or LOS compared with nonobese patients. After adjusting for the effects of morbid obesity, morbidly obese patients had increased risk of return to operating room. Despite literature describing the many perioperative risks of obesity, our analysis showed only increased reoperation for obese patients with diverticulitis.

Systems genetics applications in metabolism research.

The common forms of metabolic diseases are highly complex, involving hundreds of genes, environmental and lifestyle factors, age-related changes, sex differences and gut-microbiome interactions. Systems genetics is a population-based approach to address this complexity. In contrast to commonly used 'reductionist' approaches, such as gain or loss of function, that examine one element at a time, systems genetics uses high-throughput 'omics' technologies to quantitatively assess the many molecular differences among individuals in a population and then to relate these to physiologic functions or disease states. Unlike genome-wide association studies, systems genetics seeks to go beyond the identification of disease-causing genes to understand higher-order interactions at the molecular level. The purpose of this review is to introduce the systems genetics applications in the areas of metabolic and cardiovascular disease. Here, we explain how large clinical and omics-level data and databases from both human and animal populations are available to help researchers place genes in the context of pathways and networks and formulate hypotheses that can then be experimentally examined. We provide lists of such databases and examples of the integration of reductionist and systems genetics data. Among the important applications emerging is the development of improved nutritional and pharmacological strategies to address the rise of metabolic diseases.

Knowledge Discovery in Clinical Data

The information about patients and their medical condition are stored in a large clinical database. In this data the different patterns and relationship give new medicinal learning. To find this hidden knowledge several methods and techniques are developed. The research proposed a data mining technique in huge clinical database for searching the relationships. This data mining technique is known as Knowledge Discovery in Databases. This research defines different methods and process of data mining in clinical database.

Predicting 30-Day Hospital Readmission Risk in a National Cohort of Patients with Cirrhosis.

Early hospital readmission for patients with cirrhosis continues to challenge the healthcare system. Risk stratification may help tailor resources, but existing models were designed using small, single-institution cohorts or had modest performance. We leveraged a large clinical database from the Department of Veterans Affairs (VA) to design a readmission risk model for patients hospitalized with cirrhosis. Additionally, we analyzed potentially modifiable or unexplored readmission risk factors. A national VA retrospective cohort of patients with a history of cirrhosis hospitalized for any reason from January 1, 2006, to November 30, 2013, was developed from 123 centers. Using 174 candidate variables within demographics, laboratory results, vital signs, medications, diagnoses and procedures, and healthcare utilization, we built a 47-variable penalized logistic regression model with the outcome of all-cause 30-day readmission. We excluded patients who left against medical advice, transferred to a non-VA facility, or if the hospital length of stay was greater than 30days. We evaluated calibration and discrimination across variable volume and compared the performance to recalibrated preexisting risk models for readmission. We analyzed 67,749 patients and 179,298 index hospitalizations. The 30-day readmission rate was 23%. Ascites was the most common cirrhosis-related cause of index hospitalization and readmission. The AUC of the model was 0.670 compared to existing models (0.649, 0.566, 0.577). The Brier score of 0.165 showed good calibration. Our model achieved better discrimination and calibration compared to existing models, even after local recalibration. Assessment of calibration by variable parsimony revealed performance improvements for increasing variable inclusion well beyond those detectable for discrimination.

The Economic Burden of Patients with Eating Disorders to Healthcare Providers: A 27-Year Retrospective Record Linked Electronic Cohort Study

Background: 70 million people worldwide suffer from an eating disorder (ED) and long-term care is often needed. Patients are often young and vulnerable yet ambivalent about recovery. Without specific knowledge of the disease trajectory, patients with ED can evade detection, delaying time to diagnosis and treatment, and influencing long-term outcome and grossly underestimating treatment costs. Aim: The aim of this study was to estimate the healthcare economic burden from 1990 to 2017 of a cohort of patients with a diagnosis of an ED. Methods: The linkage and hosting of data were performed in the Secure Anonymised Information Linkage (SAIL) databank using a retrospective cohort study design. The SAIL databank is a large routine clinical database covering Wales. The data used was from the Patient Episode Database for Wales, Wales Demographics Service and Welsh General Practice datasets between 01/07/1990 and 30/06/2017, which are placed in SAIL by the Welsh National Health Service (NHS) and other data holders. Findings: Between 1990 and 2017, 15,558 individuals had an ED diagnosis. Patients with ED had large costs for inpatient admissions and GP contacts. Interpretation: Routine clinical data can be used effectively to quantify some burden of costs of a mental disorder beyond service use. ED incurred high NHS costs for GP contacts and inpatient admissions. The study included patients across the spectrum of severities, irrespective of whether they are known to specialist services. The scale of costs suggest that suffering from ED is likely to cost the NHS in areas well beyond what specific mental health service provision costs. We suggest that it may be cost-effective to invest in early intervention services that can help patients recover promptly from ED and potentially prevent high long-term costs of treatment and debility. Funding: Health and Care Research Wales (Grant HRA-15-1079). Declaration of Interest: All the authors have no competing interests to declare. Ethical Approval: The study design uses anonymised data and therefore the need for ethical approval and participant consent was waived by the approving IRB (Institutional Review Board), the UK National Health Service Research Ethics Committee. Instead, the SAIL Information Governance Review Panel (IGRP), which contains members from the UK National Health Service Research Ethics Committee, experts in information governance and members of the public, approved the study, IGRP 0487. This study was carried out in Swansea University.

Pleural Effusion Outcomes in Intensive Care: Analysis of a Large Clinical Database.

Pleural effusions are common in critically ill patients. However, the management of pleural fluid on relevant clinical outcomes is poorly studied. We evaluated the impact of pleural effusion in the intensive care unit (ICU). A large observational ICU database Multiparameter Intelligent Monitoring in Intensive Care III was utilized. Analyses used matched patients with the same admission diagnosis, age, gender, and disease severity. Of 50 765, 3897 (7.7%) of critically ill adult patients had pleural effusions. Compared to patients without effusion, patients with effusion had higher in-hospital (38.7% vs 31.3%, P < .0001), 1-month (43.1% vs 36.1%, P < .0001), 6-month (63.6% vs 55.7%, P < .0001), and 1-year mortality (73.8% vs 66.1%, P < .0001), as well as increased length of hospital stay (17.6 vs 12.7 days, P < .0001), ICU stay (7.3 vs 5.1 days, P < .0001), need for mechanical ventilation (63.1% vs 55.7%, P < .0001), and duration of mechanical ventilation (8.7 vs 6.3 days, P < .0001). A total of 1503 patients (38.6%) underwent pleural fluid drainage. Patients in the drainage group had higher in-hospital (43.9% vs 35.4%, P = .0002), 1-month (47.7% vs 39.7%, P = .0005), 6-month (67.1% vs 61.8%, P = .0161), and 1-year mortality (77.1% vs 72.1%, P = .0147), as well as increased lengths of hospital stay (22.1 vs 16.0 days, P < .0001), ICU stay (9.2d vs 6.4 days, P < .0001), and duration of mechanical ventilation (11.7 vs 7.1 days, P < .0001). The presence of a pleural effusion was associated with increased mortality in critically ill patients regardless of disease severity. Drainage of pleural effusion was associated with worse outcomes in a large, heterogeneous cohort of ICU patients.

Development and validation of a case-finding algorithm for neck and back pain in the Canadian Armed Forces using health administrative data

Introduction: In military organizations, neck and back pain are a leading cause of clinical encounters, medical evacuations out of theatres of operations, and involuntary release from service. However, tools to efficiently and accurately study these conditions in Canadian Armed Forces (CAF) personnel are lacking, and little is known about their distribution across the Canadian military. Methods: We reviewed the medical charts of 691 randomly sampled CAF personnel, and determined whether these subjects had suffered from neck or back pain at any point during the 2016 calendar year. We then developed an algorithm to identify neck or back pain patients, using large clinical and administrative databases. The algorithm was then validated by comparing its output to the results of our medical chart review. Results: Of the 691 randomly sampled subjects, 190 (27%) had experienced neck or back pain at some point during the 2016 calendar year, 43% of whom had experienced chronic pain (i.e. pain lasting for at least 90 consecutive days). Our final algorithm correctly identified 65% of all patients with past-year pain, and 80% of patients with past-year chronic pain. Overall, the algorithm’s measures of diagnostic accuracy were as follows: 65% sensitivity, 97% specificity, 91% positive predictive value, and 88% negative predictive value. Discussion: We have developed an algorithm that can be used to identify neck and back pain in CAF personnel efficiently. This algorithm is a novel research and surveillance tool that could be used to provide the epidemiological data needed to guide future intervention and prevention efforts.

Increased body mass index linked to greater short- and long-term survival in sepsis patients: A retrospective analysis of a large clinical database

ObjectivesWe investigated the impact of obesity (proxied as body mass index (BMI)), on short- and long-term mortality in sepsis patients. MethodsWe conducted a retrospective analysis with adult sepsis ICU patients in a US medical institution from 2001 to 2012 in the MIMIC-III database. The WHO BMI categories were used. Multivariate logistic regression assessed the relationships between BMI and 30-day and 1-year mortality. ResultsIn total, 5563 patients were enrolled. Obese patients tended to be younger (P<0.001), to be female (P<0.001), to acquire worse SOFA scores (P<0.001), and to receive more aggressive treatment compared with their normal weight counterparts. Obese patients had notably longer mechanical ventilation periods and ICU and hospital lengths of stay (LOSs). In the final model, overweight and obese patients had lower 30-day (OR 0.77, 95% CI 0.66–0.91; OR 0.65, 95% CI 0.56–0.77, respectively) and 1-year (OR 0.83, 95% CI 0.71–0.96; OR 0.70, 95% CI 0.60–0.81, respectively) mortality risks than normal weight patients. In contrast, underweight patients had worse 30-day and 1-year outcomes compared with normal weight patients (P=0.01, P<0.001, respectively). In morbidly obese, severe sepsis and septic shock patients, obesity remained protective. ConclusionsObesity was correlated with short- and long-term survival advantages in sepsis patients.

Effects of weight change on apolipoprotein B-containing emerging atherosclerotic cardiovascular disease (ASCVD) risk factors

Background and aimsNon-high-density (HDL)-cholesterol, low-density lipoprotein (LDL)-particle number, apolipoprotein B, lipoprotein(a) (Lp(a)), and small-dense (sdLDL) and large-buoyant (lbLDL) LDL-subfractions are emerging apo B-containing atherosclerotic cardiovascular disease (ASCVD) risk factors. Current guidelines emphasize lifestyle, including weight loss, for ASCVD risk management. Whether weight change affects these emerging risk factors beyond that predicted by traditional triglyceride and LDL-cholesterol measurements remains to be determined.MethodRegression analyses of fasting ∆apo B-containing lipoproteins vs. ∆BMI were examined in a large anonymized clinical laboratory database of 33,165 subjects who did not report use of lipid-lowering medications. Regression slopes (±SE) were estimated as: *∆mmol/L per ∆kg/m2, †∆g/L per ∆kg/m2, ‡∆% per ∆kg/m2, and §∆μmol/L per ∆kg/m2.ResultsWhen adjusted for age, ∆BMI was significantly related to ∆nonHDL-cholesterol (males: 0.0238 ± 0.0041, P = 7.9 × 10− 9; females: 0.0330 ± 0.0037, P < 10− 16)*, ∆LDL-particles (males: 0.0128 ± 0.0024, P = 2.1 × 10− 7; females: 0.0114 ± 0.0022, P = 3.2 × 10− 7)*, ∆apo B (males: 0.0053 ± 0.0010, P = 7.9 × 10− 8; females: 0.0073 ± 0.0009, P = 2.2 × 10− 16)†, ∆sdLDL (males: 0.0125 ± 0.0015, P = 2.2 × 10− 16; females: 0.0128 ± 0.0012, P < 10− 16)*, ∆percent LDL carried on small dense particles (%sdLDL, males: 0.296 ± 0.035, P < 10− 16; females: 0.221 ± 0.023, P < 10− 16)‡, ∆triglycerides (males: 0.0358 ± 0.0049, P = 2.0 × 10− 13; females: 0.0304 ± 0.0029, P < 10− 16)*, and ∆LDL-cholesterol (males: 0.0128 ± 0.0034, P = 0.0002; females: 0.0232 ± 0.0031, P = 1.2 × 10− 13)* in both males and females. Age-adjusted ∆BMI was significantly related to ∆lbLDL in females (0.0098 ± 0.0024, P = 3.9 × 10− 5)* but not males (0.0007 ± 0.0026, P = 0.78)*. Female showed significantly greater increases in ∆LDL-cholesterol (P = 0.02) and ∆lbLDL (P = 0.008) per ∆BMI than males. ∆BMI had a greater effect on ∆LDL-cholesterol measured directly than indirect estimate of ∆LDL-cholesterol from the Friedewald equation. When sexes were combined and adjusted for age, sex, ∆triglycerides and ∆LDL-cholesterol, ∆BMI retained residual associations with ∆nonHDL-cholesterol (0.0019 ± 0.0009, P = 0.03)*, ∆LDL-particles (0.0032 ± 0.0010, P = 0.001)*, ∆apo B (0.0010 ± 0.0003, P = 0.0008)†, ∆Lp(a) (− 0.0091 ± 0.0021, P = 1.2 × 10− 5)§, ∆sdLDL (0.0001 ± 0.0000, P = 1.6 × 10− 11)* and ∆%sdLDL (0.151 ± 0.018, P < 10− 16) ‡.ConclusionsEmerging apo B-containing risk factors show associations with weight change beyond those explained by the more traditional triglyceride and LDL-cholesterol measurements.

Association of Sex With Clinical Outcome in Critically Ill Sepsis Patients: A Retrospective Analysis of the Large Clinical Database MIMIC-III.

ABSTRACTIntroduction:The objective of our study was to explore the association between sex and clinical outcome in sepsis patients in a large, diverse population.Materials and Methods:We analyzed 6,134 adult patients with sepsis from the critical care units of Beth Israel Deaconess Medical Center between 2001 and 2012. Study data were retrospectively extracted from Medical Information Mart for Intensive Care-III, a multiparameter intensive care database.Results:There were 2,677 (43.6%) female and 3,457 (56.4%) male patients. Compared with female patients, male patients with sepsis had a higher 1-year mortality rate (55.6% vs. 51.4%, P = 0.001), and so did the 90-day mortality rate (45.1% vs. 42.1%, P = 0.018). 33.8% of male and 31.3% of female patients with sepsis died during hospitalization (P = 0.041). The median length of hospitalization and intensive care unit (ICU) stay for male patients was 19.54 and 7.54 days, while that for female patients was 16.49 and 6.75 days (P < 0.001, P = 0.002, respectively). Male patients were more likely to require dialysis therapy (P = 0.109), ventilation support (P = 0.012) and more vasoactive agents (dopamine P = 0.113, norepinephrine P = 0.016, and epinephrine P = 0.093) during the ICU period than female patients. Our Cox proportional hazard regression model confirmed that the risk of death within 1 year of ICU admission in male patients is 1.083 times that in female.Conclusion:Female patients with sepsis have better clinical outcomes than male patients in terms of mortality and length of hospitalization and ICU stay.

Risk factors for childhood and adult primary brain tumors.

Primary brain tumors account for ~1% of new cancer cases and ~2% of cancer deaths in the United States; however, they are the most commonly occurring solid tumors in children. These tumors are very heterogeneous and can be broadly classified into malignant and benign (or non-malignant), and specific histologies vary in frequency by age, sex, and race/ethnicity. Epidemiological studies have explored numerous potential risk factors, and thus far the only validated associations for brain tumors are ionizing radiation (which increases risk in both adults and children) and history of allergies (which decreases risk in adults). Studies of genetic risk factors have identified 32 germline variants associated with increased risk for these tumors in adults (25 in glioma, 2 in meningioma, 3 in pituitary adenoma, and 2 in primary CNS lymphoma), and further studies are currently under way for other histologic subtypes, as well as for various childhood brain tumors. While identifying risk factors for these tumors is difficult due to their rarity, many existing datasets can be leveraged for future discoveries in multi-institutional collaborations. Many institutions are continuing to develop large clinical databases including pre-diagnostic risk factor data, and developments in molecular characterization of tumor subtypes continue to allow for investigation of more refined phenotypes. Key Point 1. Brain tumors are a heterogeneous group of tumors that vary significantly in incidence by age, sex, and race/ethnicity.2. The only well-validated risk factors for brain tumors are ionizing radiation (which increases risk in adults and children) and history of allergies (which decreases risk).3. Genome-wide association studies have identified 32 histology-specific inherited genetic variants associated with increased risk of these tumors.

Dementia-related neuropsychiatric symptoms: inequalities in pharmacological treatment and institutionalization.

BackgroundDementia-related neuropsychiatric symptoms (NPS) are the main determinant of family stress and institutionalization of patients. This study aimed to identify inequalities by gender and socioeconomic status in the management of NPS in patients diagnosed with dementia.MethodsAn observational study was carried out to study all the cases of dementia in the corporate database of the Basque Health Service (29,864 patients). The prescription of antipsychotics and antidepressants and admission to a nursing home were used to establish the presence of NPS. The socioeconomic status of individuals was classified by a deprivation index. Logistic regressions were used to identify drivers for drug prescriptions and institutionalization.ResultsNPS are poorly recorded in the clinical databases (12%). Neuropsychiatric symptoms were severe enough in two thirds of patients with dementia to be treated with psychoactive medication. Institutionalization showed an increase from those who did not receive medication to those who had been prescribed antidepressants (OR: 1.546), antipsychotics (OR: 2.075) or both (OR: 2.741). The resulting inequalities were the increased prescription of antidepressant drugs in women and more nursing-home admissions for women who were the least socioeconomically deprived and men who were the most deprived.ConclusionsIn large clinical databases, psychoactive drugs prescriptions can be useful to underscore the considerable burden of dementia-related NPS. Specific tools are needed to monitor social and health care programs targeted to dementia-related NPS from a population perspective. Programs aimed at reducing the family burden of care of dementia patients at home become the key elements in reducing inequalities in these patients’ care. Socioeconomic status is the most important driver of inequality, and gender inequality may simply be hidden within the social environment. Integrated programs boosting the continuity of care are an objective for which compliance could be measured according to the NPS coding in the electronic health record.

MON-299 KIDNEY OUTCOMES ASSOCIATED WITH INITIATION OF SODIUM GLUCOSE CO-TRANSPORTER 2 INHIBITION VERSUS OTHER GLUCOSE LOWERING DRUGS - AN ANALYSIS FROM THE CVD-REAL STUDY

Recent cardiovascular outcome trials have shown that sodium glucose co-transporter 2 inhibitors (SGLT-2i) slow progression of chronic kidney disease in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to patients with type 2 diabetes treated in clinical practice is unknown. The purpose of this study was to determine kidney outcomes and estimated glomerular filtration rate (eGFR) decline in patients initiating SGLT-2i versus other glucose lowering drugs (oGLDs) in a real world setting. New users of SGLT-2i and oGLDs were identified via claims, medical records, and national registries in Japan and Israel. Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching. Propensity score included amongst others baseline eGFR and eGFR slope prior to SGLT-2i or oGLDs initiation (index date). After propensity score matching more than 25000 individuals were included. The primary outcome measure was the total eGFR slope after the index date calculated with a linear mixed regression model. Differences in eGFR slope between SGLT-2is and oGLDs were calculated by country and pooled using weighted meta-analyses. Additional outcomes were a composite endpoint of 50% eGFR decline or end-stage kidney disease (ESKD) and their individual components. Hazard ratios (HRs) for these outcomes, calculated with Cox proportional hazard models, were assessed by country and pooled using weighted meta-analysis. After propensity matching, there were 14120 episodes of treatment initiation in each group. Dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, luseogliflozin and tofogliflozin accounted for 30.1%, 62.8%, 1.6%, 3.3%, 0.9%, and 1.3% of SGLT2i initiation, respectively. At the index date, mean age was 61.5 years, eGFR was 91.5 ml/min/1.73m2, HbA1c was 8.4%, and 40.4% were female. Annual eGFR change prior to oGLDs or SGLT2i initiation was −0.75 and −0.71 ml/min/1.73m2/year, respectively. The annual rate of eGFR change during oGLDs was −1.0 (95%CI −1.1 to −0.9) ml/min/1.73m2/year and during SGLT2i treatment 0.0 ml/min/1.73m2/year (95%CI −0.1 to 0.1; p vs. oGLDs <0.001). During a mean follow-up of 18 months, 52 (0.37%) patients reached the primary renal endpoint in the SGLT2i group and 104 (0.74%) in the oGLDs group (hazard ratio 0.51 [95%CI 0.36 to 0.71]). Use of SGLT2i versus oGLD was associated with a lower risk of the individual components of the endpoint: ESKD (HR 0.32 [95%CI 0.15 to 0.71); 50% eGFR decline (HR 0.53 [95%CI 0.38 to 0.76]). These effects were consistent across countries. In this large international real world clinical practice database of patients with type 2 diabetes, SGLT2i use was associated with a slower rate of renal function decline and lower risk of clinically meaningful renal events compared to oGLDs. These data indicate that the beneficial effects of SGLT2i on kidney function as observed in clinical trials translate to daily clinical practice.

Outcomes in conventional laparoscopic versus robotic-assisted primary bariatric surgery: a retrospective, case-controlled study of the MBSAQIP database.

IntroductionRobotic-assisted bariatric surgery is increasingly performed. There remains controversy about the overall benefit of robotic-assisted (RBS) compared to conventional laparoscopic (LBS) bariatric surgery. In this study, we used a large national risk-stratified bariatric clinical database to compare outcomes between robotic and laparoscopic gastric bypass (RNYGB) and sleeve gastrectomy (SG).MethodsA retrospective analysis of the 2015 and 2016 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Participant Use Data File (PUF) was performed. Primary robotic and laparoscopic RYNGB and SG were analyzed. Descriptive analysis was performed of the unmatched cohorts, followed by 1:3 case-controlled matching. Cases and controls were matched by patient demographics and pre-operative comorbidities, and peri-operative outcomes compared.Results77,991 Roux-en-Y gastric bypass (RnYGB) (7.5% robotic-assisted) and 189,503 SG (6.8% robotic-assisted) cases were identified. Operative length was significantly higher in both the robotic-assisted RnYGB and SG cohorts (p < 0.0001). Outcomes were similar between the robotic-assisted and laparoscopic RnYGB cohorts, except a lower mortality rate (p = 0.05), transfusion requirement (p = 0.005), aggregate bleeding (p = 0.04), and surgical site infections (SSI) (p = 0.006) in the robotic-assisted cohort. Outcomes were also similar between robotic-assisted and laparoscopic SG, except for a longer length of stay (p < 0.0001) and higher rates of conversion (p < 0.0001), 30-day intervention (p = 0.01), operative drain present (p < 0.0001), sepsis (p = 0.01), and organ space SSI (p = 0.0002) in the robotic cohort. Bleeding was lower in the robotic SG cohort and mortality was similar.ConclusionBoth robotic-assisted and laparoscopic RnYGB and SG are overall very safe. Robotic-assisted gastric bypass is associated with a lower mortality and morbidity; however, a clear benefit for robotic-assisted SG compared to laparoscopic SG was not seen. Given the longer operative and hospital duration, robotic SG is not cost-effective.Electronic supplementary materialThe online version of this article (10.1007/s00464-019-06915-7) contains supplementary material, which is available to authorized users.

Ml-RECIST: Machine learning to estimate RECIST in patients with NSCLC treated with PD-(L)1 blockade.

9052 Background: Real-world evidence (RWE) is increasingly important for discovery and may be an opportunity for regulatory approval. Effective use of RWE relies on determining treatment-specific outcomes, such as overall response rate (ORR) and progression-free survival (PFS), which are challenging to accurately evaluate retrospectively and at scale. We hypothesized the use of machine learning of text radiology reports from patients with NSCLC treated with PD-1 blockade could be used to train a model that estimates RECIST-defined outcomes. Methods: 2753 imaging reports from 453 patients with advanced NSCLC treated with PD-1 blockade were collected and separated into independent training (80%, n = 362) and validation (20%, n = 92) cohorts. Reports were limited to interval of PD-1 blockade. RECIST reads performed by thoracic radiologists on all patients served as “gold standard” to determine ORR, occurrence of, and date of progression. Baseline reports were compared to all follow up reports to determine machine-learning RECIST (ml-RECIST). A four layers neural-network model for classification was proposed to solve the three above tasks. Results: In the training cohort, ml-RECIST best estimated ORR by RECIST (accuracy CR/PR 84%, SD 82%, POD 91%). ml-RECIST estimated PFS by RECIST accurately predicting progression occurred at any time (86%) and exact progression date (65%). Date of progression was closely correlated (Pearson’s r coefficient = 0.91, 95% CI:0.89-0.94, p &lt; 0.001) in patients determined to have progressed by both methods. Similar accuracy of ml-RECIST was observed in the validation cohort (accuracy CR/PR 84%, SD 80%, POD 90%; progression occurred 86%, progression date 72%). Accuracy was consistent when RECIST reads were performed prospectively as part of clinical trials vs retrospectively for standard of care treatment (e.g. CR/PR 82% vs 88%, respectively). ml-RECIST-defined response similarly determined improvement in overall survival compared to RECIST (HR = 0.19, p &lt; 0.001 vs HR = 0.26, p &lt; 0.001 respectively). Conclusions: Machine learning-RECIST ("ml-RECIST") accurately estimates outcomes using imaging text reports. ml-RECIST may be tool to determine outcomes expeditiously and at scale for use in RWE studies, enabling more useful and reliable applications of large clinical databases.

Circadian biology in translation

The past several decades has seen an explosion of growth in mechanistic understanding of circadian clocks in several model organisms, including humans. However, translation of that knowledge into actionable medical intervention(s) has been slow to non‐existent. Here, I will discuss some of the reasons why this is as well as our efforts to mitigate this using systems biology approaches. I will talk about our recent progress in understanding the molecular output of the clock in the mouse and humans, including identifying new opportunities for circadian dosing time in improving drug action ‐‐ hypothesis‐driven, mechanistic circadian medicine. I will talk about our efforts to test these hypothesis prospectively in model organisms and retrospectively in large clinical databases. Finally, I will discuss future opportunities and challenges.Support or Funding InformationThis work is supported by the National Institute of Neurological Disorders and Stroke (2R01NS054794 to JBH and Andrew Liu; and 1R21NS101983 to Tom Kilduff and JBH), the National Heart, Lung, and Blood Institute (R01HL138551 to Eric Bittman and JBH), and National Human Genome Research Institute (2R01HG005220 to Rafa Irizarry and JBH.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of Timing and Duration of Statin Exposure on Risk of Hip or Knee Revision Arthroplasty: A Population-based Cohort Study.

To determine whether the timing and duration of statin exposure following total hip/knee arthroplasty (THA/TKA) influence the risk of revision arthroplasty. Subjects from the Clinical Practice Research Datalink, a large population-based clinical database, who had THA/TKA from 1988 to 2016, were included. Propensity score adjusted Cox regression models were used to determine the association between statin exposure and the risk of revision THA/TKA, (1) at any time, and (2) if first exposed 0-1, 1-5, or > 5 years following THA/TKA. We also investigated the effect of duration of statin exposure (< 1, 1-2, 2-3, 3-4, 4-5, > 5 yrs). The study included 151,305 participants. There were 65,032 (43%) exposed to statins during followup and 3500 (2.3%) had revision arthroplasty. In a propensity score adjusted model, exposure to statins was associated with a reduced risk of revision arthroplasty (HR 0.82, 95% CI 0.75-0.90). Participants first exposed within 1 year and between 1 and 5 years following THA/TKA (vs unexposed) had a reduced risk of revision arthroplasty (HR 0.82, 95% CI 0.74-0.91 and HR 0.76, 95% CI 0.65-0.90, respectively). In relation to duration of statin therapy, participants exposed for more than 5 years in total (vs < 1 yr) had a reduced risk of revision (HR 0.74, 95% CI 0.62-0.88). Statin therapy initiated up to 5 years following THA/TKA may reduce the risk of revision arthroplasty.

Failure to detect an association between self-reported traumatic brain injury and Alzheimer's disease neuropathology and dementia

IntroductionRecent research with neuropathologic or biomarker evidence of Alzheimer's disease (AD) casts doubt on traumatic brain injury (TBI) as a risk factor for AD. We leveraged the National Alzheimer's Coordinating Center to examine the association between self-reported TBI with loss of consciousness and AD neuropathologic changes, and with baseline and longitudinal clinical status. MethodsThe sample included 4761 autopsy participants (453 with remote TBI with loss of consciousness; 2822 with AD neuropathologic changes) from National Alzheimer's Coordinating Center. ResultsSelf-reported TBI did not predict AD neuropathologic changes (P > .10). Reported TBI was not associated with baseline or change in dementia severity or cognitive function in participants with or without autopsy-confirmed AD. DiscussionSelf-reported TBI with loss of consciousness may not be an independent risk factor for clinical or pathological AD. Research that evaluates number and severity of TBIs is needed to clarify the neuropathological links between TBI and dementia documented in other large clinical databases.