Impact of event notification services on timely follow-up and rehospitalization among primary care patients at two Veterans Affairs Medical Centers

ObjectiveTo examine the effectiveness of event notification service (ENS) alerts on health care delivery processes and outcomes for older adults.Materials and methodsWe deployed ENS alerts in 2 Veterans Affairs (VA) medical centers using regional health information exchange (HIE) networks from March 2016 to December 2019. Alerts targeted VA-based primary care teams when older patients (aged 65+ years) were hospitalized or attended emergency departments (ED) outside the VA system. We employed a concurrent cohort study to compare postdischarge outcomes between patients whose providers received ENS alerts and those that did not (usual care). Outcome measures included: timely follow-up postdischarge (actual phone call within 7 days or an in-person primary care visit within 30 days) and all-cause inpatient or ED readmission within 30 days. Generalized linear mixed models, accounting for clustering by primary care team, were used to compare outcomes between groups.ResultsCompared to usual care, veterans whose primary care team received notification of non-VA acute care encounters were 4 times more likely to have phone contact within 7 days (AOR = 4.10, P < .001) and 2 times more likely to have an in-person visit within 30 days (AOR = 1.98, P = .007). There were no significant differences between groups in hospital or ED utilization within 30 days of index discharge (P = .057).DiscussionENS was associated with increased timely follow-up following non-VA acute care events, but there was no associated change in 30-day readmission rates. Optimization of ENS processes may be required to scale use and impact across health systems.ConclusionGiven the importance of ENS to the VA and other health systems, this study provides guidance for future research on ENS for improving care coordination and population outcomes.Trial RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02689076","term_id":"NCT02689076"}}NCT02689076. “Regional Data Exchange to Improve Care for Veterans After Non-VA Hospitalization.” Registered February 23, 2016.     

Is rs759853 polymorphism in promoter of aldose reductase gene a risk factor for diabetic nephropathy? A meta-analysis

Background

So far, a number of case-control or cohort studies have been carried out to investigate the relationship between rs759853 polymorphism in the promoter of aldose reductase (AR) gene and the risk of diabetic nephropathy (DN). However, the results have generated considerable controversy. We performed this study to clarify the linkage between this gene mutation and the risk of DN.

Methods

A comprehensive literature search of electronic databases and a well-organized meta-analysis were conducted.

Results

Twelve comparisons and 4,735 individuals from nine published case-control or cohort studies were included finally. From none to large heterogeneity was observed, therefore, both fixed and random models were used. Significant differences were found between AR rs759853 polymorphism and susceptibility of DN from both type 1 and type 2 diabetes in all genetic models (allele contrast, OR = 1.37, CI (1.18, 1.59), P < 0.0001; additive model, OR = 1.78, CI (1.25, 2.53), P = 0.01; recessive model OR = 1.33 CI (1.08, 1.63), P = 0.008; dominant model, OR = 1.52, CI (1.26, 1.84), P < 0.0001; codominance model OR = 1.30 (1.15, 1.47), P < 0.0001). In stratified meta-analyses for type 2 diabetes by ethnicity, the significant relationship was found in allele contrast and dominant model in Caucasians, and in allele contrast and codominance model in Asians. However, data do not support the linkage between this gene mutation and the progression of DN. There was no significant publication bias.

Conclusions

The evidence currently available shows that the AR rs759853 polymorphism may correlate with the susceptibility of DN. However, data do not support the association between this DNA variation and the progression of DN.     

Association of CYP1A1 MspI polymorphism in the esophageal cancer risk: a meta-analysis in the Chinese population

Background

Although many epidemiologic studies have investigated the CYP1A1 MspI gene polymorphisms and their associations with esophageal cancer (EC), definite conclusions cannot be drawn. To clarify the effects of CYP1A1 MspI polymorphisms on the risk of EC, a meta-analysis was performed in Chinese population.

Methods

Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till October 2014. Pooled ORs and 95% CIs were used to assess the strength of the associations.

Results

A total of 13 studies including 1,519 EC cases and 1,962 controls were involved in this meta-analysis. Overall, significant association was found between CYP1A1 MspI polymorphism and EC risk when all studies in the Chinese population pooled into this meta-analysis (C vs. T: OR = 1.25, 95% CI = 1.04 to 1.51; CC + CT vs. TT: OR = 1.35, 95% CI = 1.06 to 1.72; CC vs. TT + CT: OR = 1.35, 95% CI = 1.03 to 1.76). When we performed stratified analyses by geographical locations, histopathology type, and source of control, significantly increased risks were found in North China (C vs. T: OR = 1.38, 95% CI = 1.12 to 1.70; CC vs. TT: OR = 1.72, 95% CI = 1.16 to 2.56; CC + CT vs. TT: OR = 1.52, 95% CI = 1.14 to 2.02; CC vs. TT + CT: OR = 1.55, 95% CI = 1.17 to 2.06), in the population-based studies (C vs. T: OR = 1.22, 95% CI = 1.05 to 1.42; CC vs. TT: OR = 1.38, 95% CI = 1.02 to 1.88; CC + CT vs. TT: OR = 1.36, 95% CI = 1.10 to 1.69; CC vs. TT + CT: OR = 1.43, 95% CI = 1.13 to 1.81) and ESCC (C vs. T: OR = 1.17, 95% CI = 1.04 to 1.32; CC + CT vs. TT: OR = 1.28, 95% CI = 1.08 to 1.52).

Conclusions

This meta-analysis provides the evidence that CYP1A1 MspI polymorphism may contribute to the EC development in the Chinese population.     

Comparison of the safety and efficacy of biodegradable polymer drug-eluting stents versus durable polymer drug-eluting stents: a meta-analysis

Background

A meta-analysis was conducted to assess the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DESs).

Methods

PubMed, Science Direct, China National Knowledge Infrastructure, and Chongqing VIP databases were searched for randomized controlled trials comparing the safety and efficacy of BP-DESs versus durable polymer drug-eluting stents (DP-DESs). Efficacy included the prevalence of target lesion revascularization (TLR), target vessel revascularization (TVR), and late lumen loss (LLL), and safety of these stents at the end of follow-up for the selected research studies were compared.

Results

A total of 16 qualified original studies that addressed a total of 22,211 patients were included in this meta-analysis. In regard to efficacy, no statistically significant difference in TLR (odds ratio (OR) = 0.94, P = 0.30) or TVR (OR 1.01, P = 0.86) was observed between patients treated with BP-DESs and those with DP-DESs. However, there were significant differences in in-stent LLL (weighted mean difference [WMD] = −0.07, P = 0.005) and in-segment LLL (WMD = −0.03, P = 0.05) between patients treated with BP-DESs and with DP-DESs. In terms of safety, there was no significant difference in overall mortality (OR 0.97, P = 0.67), cardiac death (OR 0.99, P = 0.90), early stent thrombosis (ST) and late ST (OR 0.94, P = 0.76; OR 0.96, P = 0.73), or myocardial infarction (MI) (OR 0.99, P = 0.88) between patients treated with BP-DESs and with DP-DESs. However, there was a statistically significant difference in very late ST (OR 0.69, P = 0.007) between these two groups. In addition, the general trend of the rates of TVR and TLR of BP-DESs groups was lower than DP-DESs groups after a 1-year follow-up.

Conclusion

BP-DESs are safe, efficient, and exhibit superior performance to DP-DESs with respect to reducing the occurrence of very late ST and LLL. The general trend of the rates of TVR and TLR of BP-DESs groups was lower than DP-DESs groups after a 1-year follow-up.     

Development of a standardized laparoscopic caecum resection model to simulate laparoscopic appendectomy in rats

Background

Laparoscopic appendectomy (LA) has become one of the most common surgical procedures to date. To improve and standardize this technique further, cost-effective and reliable animal models are needed.

Methods

In a pilot study, 30 Wistar rats underwent laparoscopic caecum resection (as rats do not have an appendix vermiformis), to optimize the instrumental and surgical parameters. A subsequent test study was performed in another 30 rats to compare three different techniques for caecum resection and bowel closure.

Results

Bipolar coagulation led to an insufficiency of caecal stump closure in all operated rats (Group 1, n = 10). Endoloop ligation followed by bipolar coagulation and resection (Group 2, n = 10) or resection with a LigaSure™ device (Group 3, n = 10) resulted in sufficient caecal stump closure.

Conclusions

We developed a LA model enabling us to compare three different caecum resection techniques in rats. In conclusion, only endoloop closure followed by bipolar coagulation proved to be a secure and cost-effective surgical approach.     

Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C

Background

Given the important contribution of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system to the generation of reactive oxygen species induced by hepatitis C virus (HCV), we investigated two single nucleotide polymorphisms (SNPs) in the putative regulatory region of the genes encoding NADPH oxidase 4 catalytic subunit (NOX4) and its regulatory subunit p22phox (CYBA) and their relation with metabolic and histological variables in patients with HCV.

Methods

One hundred seventy eight naïve HCV patients (49.3% male; 65% HCV genotype 1) with positive HCV RNA were genotyped using specific primers and fluorescent-labeled probes for SNPs rs3017887 in NOX4 and −675 T → A in CYBA.

Results

No association was found between the genotype frequencies of NOX4 and CYBA SNPs and inflammation scores or fibrosis stages in the overall population. The presence of the CA + AA genotypes of the NOX4 SNP was nominally associated with a lower alanine aminotransferase (ALT) concentration in the male population (CA + AA = 72.23 ± 6.34 U/L versus CC = 100.22 ± 9.85; mean ± SEM; P = 0.05). The TT genotype of the CYBA SNP was also nominally associated with a lower ALT concentration in the male population (TT = 84.01 ± 6.77 U/L versus TA + AA = 109.67 ± 18.37 U/L; mean ± SEM; P = 0.047). The minor A-allele of the NOX4 SNP was inversely associated with the frequency of metabolic syndrome (MS) in the male population (odds ratio (OR): 0.15; 95% confidence interval (CI): 0.03 to 0.79; P = 0.025).

Conclusions

The results suggest that the evaluated NOX4 and CYBA SNPs are not direct genetic determinants of fibrosis in HCV patients, but nevertheless NOX4 rs3017887 SNP could indirectly influence fibrosis susceptibility due to its inverse association with MS in male patients.     

Genetic polymorphisms of glutathione S-transferase M1 and T1, and evaluation of oxidative stress in patients with non-small cell lung cancer

Background

Our objective is to investigate the genetic polymorphisms of the glutathione S-transferase M1 and T1 genes (GSTM1 and GSTT1) and evaluate oxidative damage in patients with non-small lung cancer (N-SCLC).

Methods

One hundred and ten patients with N-SCLC and 100 controls are included in this case-control study. Multiplex polymerase chain reaction (PCR) analyses were used to identify the genotypes. The activities of malondialdehyde (MDA) and nitric oxide (NO) and total antioxidant capacity (T-AOC) were detected by spectroscopic analysis.

Results

The frequencies of the GSTM1, T1, and GSTM1/T1 null genotypes in the patient group were significantly higher than that in the control group (OR = 2.071, P = 0.009; OR = 1.900, P = 0.024; OR = 3.258, P = 0.003). The activities of MDA and NO were significantly higher in the patient group than that in the control group (P <0.001), and T-AOC was significantly lower in patient group than that in control group (P <0.001). The activities of MDA, and NO were higher but the T-AOC was lower in patients with the GSTM1, T1 and M1/T1 null genotypes than those in patients with GSTM1, T1 and M1/T1 present genotypes (P <0.001).

Conclusions

Our results suggest that oxidative damage may be play a important role in patients with N-SCLC, and that GSTM1 and GSTT1 null genotypes may predispose the cells of patients with N-SCLC to increased oxidative damage.     

Clinical implications of the quantitative detection of ID4 gene methylation in myelodysplastic syndrome

Background

Myelodysplastic syndrome (MDS) eventually transforms into acute leukemia (AL) in about 30% of patients. Hypermethylation of the inhibitor of DNA binding 4 (ID4) gene may play an important role in the initiation and development of MDS and AL. The aim of this study was to quantitatively assess ID4 gene methylation in MDS and to establish if it could be an effective method of evaluating MDS disease progression.

Methods

We examined 142 bone marrow samples from MDS patients, healthy donors and MDS-AL patients using bisulfite sequencing PCR and quantitative real-time methylation-specific PCR. The ID4 methylation rates and levels were assessed.

Results

ID4 methylation occurred in 27 patients (27/100). ID4 gene methylation was more frequent and at higher levels in patients with advanced disease stages and in high-risk subgroups according to WHO (P < 0.001, P < 0.001, respectively) and International Prognostic Scoring System (IPSS) (P = 0.002, P = 0.007, respectively) classifications. ID4 methylation levels changed during disease progression. Both methylation rates and methylation levels were significantly different between healthy donor, MDS patients and patients with MDS-AL (P < 0.001, P < 0.001, respectively). Multivariate analysis indicated that the level of ID4 methylation was an independent factor influencing overall survival. Patients with MDS showed decreased survival time with increased ID4 methylation levels (P = 0.011, hazard ratio (HR) = 2.371). Patients with ID4 methylation had shorter survival time than those without ID4 methylation (P = 0.008).

Conclusions

Our findings suggest that ID4 gene methylation might be a new biomarker for MDS monitoring and the detection of minimal residual disease.     

Characterizing physician EHR use with vendor derived data: a feasibility study and cross-sectional analysis

ObjectiveTo derive 7 proposed core electronic health record (EHR) use metrics across 2 healthcare systems with different EHR vendor product installations and examine factors associated with EHR time.Materials and MethodsA cross-sectional analysis of ambulatory physicians EHR use across the Yale-New Haven and MedStar Health systems was performed for August 2019 using 7 proposed core EHR use metrics normalized to 8 hours of patient scheduled time.ResultsFive out of 7 proposed metrics could be measured in a population of nonteaching, exclusively ambulatory physicians. Among 573 physicians (Yale-New Haven N = 290, MedStar N = 283) in the analysis, median EHR-Time₈ was 5.23 hours. Gender, additional clinical hours scheduled, and certain medical specialties were associated with EHR-Time₈ after adjusting for age and health system on multivariable analysis. For every 8 hours of scheduled patient time, the model predicted these differences in EHR time (P < .001, unless otherwise indicated): female physicians +0.58 hours; each additional clinical hour scheduled per month −0.01 hours; practicing cardiology −1.30 hours; medical subspecialties −0.89 hours (except gastroenterology, P = .002); neurology/psychiatry −2.60 hours; obstetrics/gynecology −1.88 hours; pediatrics −1.05 hours (P = .001); sports/physical medicine and rehabilitation −3.25 hours; and surgical specialties −3.65 hours.ConclusionsFor every 8 hours of scheduled patient time, ambulatory physicians spend more than 5 hours on the EHR. Physician gender, specialty, and number of clinical hours practicing are associated with differences in EHR time. While audit logs remain a powerful tool for understanding physician EHR use, additional transparency, granularity, and standardization of vendor-derived EHR use data definitions are still necessary to standardize EHR use measurement.     

Retrospective analysis of the frequency of centrofacial telangiectasia in systemic sclerosis patients treated with bosentan or ilomedin

Background

Bosentan is a dual endothelin receptor antagonist initially introduced for the treatment of pulmonary arterial hypertension and recently approved for the treatment of digital ulcers in patients with systemic sclerosis (SSc). Our clinical observations indicate that bosentan therapy may be associated with an increased frequency of centrofacial telangiectasia (TAE). Here, we sought to analyze the frequency of TAE in patients with SSc who were treated with either bosentan or the prostacyclin analog iloprost.

Methods

We conducted a retrospective analysis in 27 patients with SSc undergoing therapy with either bosentan (n = 11) or iloprost (n = 16). Standardized photodocumentations of all patients (n = 27) were obtained at a time point ten months after therapy initiation and analyzed. A subgroup of patients (bosentan: n = 6; iloprost: n = 6) was additionally photodocumented prior to therapy initiation, enabling an intraindividual analysis over the course of therapy.

Results

After ten months of therapy patients with SSc receiving bosentan showed a significantly (P = 0.0028) higher frequency of centrofacial TAE (41.6 ± 27.8) as compared to patients with SSc receiving iloprost (14.3 ± 13.1). Detailed subgroup analysis revealed that the frequency of TAE in the bosentan group (n = 6 patients) increased markedly and significantly (P = 0.027) by 44.4 after ten months of therapy (TAE at therapy initiation: 10.8 ± 5.1; TAE after ten months of therapy: 55.2 ± 29.8), whereas an only minor increase of 1.9 was observed in the iloprost group (n = 6 patients; TAE at therapy initiation: 18.3 ± 14.5; TAE after ten months of therapy: 20.2 ± 15.5), yet without reaching statistical significance (P = 0.420).

Conclusions

The use of bosentan may be associated with an increased frequency of TAE in patients with SSc. Patients should be informed about this potential adverse effect prior to therapy. Treatment options may include camouflage or laser therapy.     

Inferior mesenteric vein serves as an alternative guide for transection of the pancreatic body during pancreaticoduodenectomy with concomitant vascular resection: a comparative study evaluating perioperative outcomes

Background

Tumors of the pancreatic head often involve the superior mesenteric and portal veins. The purpose of this study was to assess perioperative outcomes after pancreaticoduodenectomy (PD) with concomitant vascular resection using the inferior mesenteric vein (IMV) as a guide for transection of the pancreatic body (Whipple at IMV, WATIMV).

Methods

One hundred thirty-seven patients had segmental vein resection during PD between January 2006 and June 2013. Depending on whether the standard approach of creating a tunnel anterior to the mesenterico-portal vein (MPV) axis was achieved for pancreatic transection, patients were subjected to a standard PD with vein resection procedure (s-PD + VR, n = 75) or a modified procedure (m-PD + VR, n = 62). Within the m-PD + VR group, 28 patients underwent the WATIMV procedure, while 34 patients underwent the usual procedure of transection, or ‘central pancreatectomy’ (c-PD + VR).

Results

The volume of intraoperative blood loss and the blood transfusion requirements were significantly greater, and the venous wall invasion and neural invasion frequency were significantly higher in the m-PD + VR group compared with the s-PD + VR group. There were no significant differences in the length of hospitalization, postoperative morbidity, and grades of complications between the two groups. Multivariate logistic regression identified intraoperative blood transfusion (P = 0.004) and vascular invasion (P = 0.008) as the predictors of postoperative morbidity. Further stratification of the entire cohort of 62 (45%) patients who underwent m-PD + VR showed a higher rate of negative resection margins (96.4%) in the WATIMV group compared with the c-PD + VR group (76.5%) (P = 0.06). The volume of intraoperative blood loss (P = 0.013), and intraoperative blood transfusion requirements (P = 0.07) were significantly greater in the c-PD + VR group compared with the WATIMV group. Furthermore, high intraoperative blood loss and tumor stage were predictive of a positive resection margin.

Conclusions

‘Whipple at the IMV (WATIMV)’ has comparable postoperative morbidity with standard PD + VR. If IMV runs into the splenic vein, it could serve as an alternative guide for transection of the pancreatic body during PD + VR.     

The quality of social determinants data in the electronic health record: a systematic review

ObjectiveThe aim of this study was to collect and synthesize evidence regarding data quality problems encountered when working with variables related to social determinants of health (SDoH).Materials and MethodsWe conducted a systematic review of the literature on social determinants research and data quality and then iteratively identified themes in the literature using a content analysis process.ResultsThe most commonly represented quality issue associated with SDoH data is plausibility (n = 31, 41%). Factors related to race and ethnicity have the largest body of literature (n = 40, 53%). The first theme, noted in 62% (n = 47) of articles, is that bias or validity issues often result from data quality problems. The most frequently identified validity issue is misclassification bias (n = 23, 30%). The second theme is that many of the articles suggest methods for mitigating the issues resulting from poor social determinants data quality. We grouped these into 5 suggestions: avoid complete case analysis, impute data, rely on multiple sources, use validated software tools, and select addresses thoughtfully.DiscussionThe type of data quality problem varies depending on the variable, and each problem is associated with particular forms of analytical error. Problems encountered with the quality of SDoH data are rarely distributed randomly. Data from Hispanic patients are more prone to issues with plausibility and misclassification than data from other racial/ethnic groups.ConclusionConsideration of data quality and evidence-based quality improvement methods may help prevent bias and improve the validity of research conducted with SDoH data.     

Joint detection of ERCC1, TUBB3, and TYMS guidance selection of docetaxel, 5-fluorouracil and cisplatin (DDP) individual chemotherapy in advanced gastric cancer patients

Background

To investigate the guidance selection of docetaxel (D), cisplatin (DDP) (C), and 5-fluorouracil (5-FU) (F) as individual chemotherapy agents via joint detection of ERCC1, TUBB3, and TYMS genes in patients with advanced gastric cancer (AGC).

Method

Clinical data of 120 patients with AGC who enrolled in our hospital between May 2009 and May 2012 were analyzed. These patients were randomly assigned to experimental and control groups. The mRNA expression of ERCC1, TUBB3, and TYMS was measured by DNA chip technology in the experimental group. Different chemotherapies were administered according to the mRNA expression levels of the three genes, while DCF chemotherapy was directly applied to the control group. Correlation between the three genes’ mRNA levels, efficiency rate, the median time to progression (MTP), median survival time (MST) and adverse reactions was evaluated.

Results

As a result, there was a significant correlation between ERCC1 and TUBB3 mRNA expression (P = 0.005), but no obvious correlation between TUBB3 and TYMS or ERCC1 and TYMS. There was also no significant difference in the efficiency rate of chemotherapy (50% versus 55%; P = 0.357) and the MTP (10 months versus 7 months; P = 0.091) between the two groups. However, there was obvious significance in MST (13.7 months versus 11.6 months; P = 0.004). Additionally, the experimental group provided us with a more effective way for controlling adverse reactions to chemotherapy.

Conclusion

Combination regimen of D, C, and F in AGC patients according to their ERCC1, TUBB3, and TYMS mRNA expression level may reduce adverse reactions and improve MST.     

Risk factors associated with medication ordering errors

ObjectiveWe utilized a computerized order entry system–integrated function referred to as “void” to identify erroneous orders (ie, a “void” order). Using voided orders, we aimed to (1) identify the nature and characteristics of medication ordering errors, (2) investigate the risk factors associated with medication ordering errors, and (3) explore potential strategies to mitigate these risk factors.Materials and MethodsWe collected data on voided orders using clinician interviews and surveys within 24 hours of the voided order and using chart reviews. Interviews were informed by the human factors–based SEIPS (Systems Engineering Initiative for Patient Safety) model to characterize the work systems–based risk factors contributing to ordering errors; chart reviews were used to establish whether a voided order was a true medication ordering error and ascertain its impact on patient safety.ResultsDuring the 16-month study period (August 25, 2017, to December 31, 2018), 1074 medication orders were voided; 842 voided orders were true medication errors (positive predictive value = 78.3 ± 1.2%). A total of 22% (n = 190) of the medication ordering errors reached the patient, with at least a single administration, without causing patient harm. Interviews were conducted on 355 voided orders (33% response). Errors were not uniquely associated with a single risk factor, but the causal contributors of medication ordering errors were multifactorial, arising from a combination of technological-, cognitive-, environmental-, social-, and organizational-level factors.ConclusionsThe void function offers a practical, standardized method to create a rich database of medication ordering errors. We highlight implications for utilizing the void function for future research, practice and learning opportunities.     

Association between plasma ADAMTS-7 levels and ventricular remodeling in patients with acute myocardial infarction

Background

The metalloproteinase family of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) degrades extracellular matrix. However, the relevance of the ADAMTS family to cardiovascular diseases remains largely unknown. The study aimed to examine plasma ADAMTS-7 levels in patients with acute myocardial infarction (AMI) and the relationship between plasma ADAMTS-7 levels and heart function.

Methods

This was a prospective study performed in 84 patients with ST-elevation myocardial infarction (STEMI), 70 patients with non-STEMI (NSTEMI), and 38 controls. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma ADAMTS-7 levels. Cardiac structure and function were assessed using two-dimensional transthoracic echocardiography. Patients were stratified according to left ventricular ejection fraction (LVEF) ≤35% or >35%.

Results

Plasma ADAMTS-7 levels were higher in patients with LVEF ≤35% compared with those with LVEF >35% (6.73 ± 2.47 vs. 3.22 ± 2.05 ng/ml, P < 0.05). Plasma ADAMTS-7 levels were positively correlated with brain natriuretic peptide (BNP), left ventricular mass index (LVMI), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD) and negatively correlated with the 6-min walk test (P < 0.05). According to the receiver operating characteristic (ROC) curve, using a cutoff value of plasma ADAMTS-7 of 5.69 ng/ml was associated with a specificity of 61.0% and a sensitivity of 87.6% for the diagnosis of heart failure after AMI. Logistic regression analysis indicated that the association between ADAMTS-7 and heart failure after AMI was independent from traditional cardiovascular risk factors and other biomarkers (odds ratio = 1.236, 95% confidence interval: 1.023 to 1.378, P = 0.021).

Conclusions

Elevated ADAMTS-7 level may be involved in ventricular remodeling after AMI.     

Multi-PheWAS intersection approach to identify sex differences across comorbidities in 59 140 pediatric patients with autism spectrum disorder

ObjectiveTo identify differences related to sex and define autism spectrum disorder (ASD) comorbidities female-enriched through a comprehensive multi-PheWAS intersection approach on big, real-world data. Although sex difference is a consistent and recognized feature of ASD, additional clinical correlates could help to identify potential disease subgroups, based on sex and age.Materials and MethodsWe performed a systematic comorbidity analysis on 1860 groups of comorbidities exploring all spectrum of known disease, in 59 140 individuals (11 440 females) with ASD from 4 age groups. We explored ASD sex differences in 2 independent real-world datasets, across all potential comorbidities by comparing (1) females with ASD vs males with ASD and (2) females with ASD vs females without ASD.ResultsWe identified 27 different comorbidities that appeared significantly more frequently in females with ASD. The comorbidities were mostly neurological (eg, epilepsy, odds ratio [OR] > 1.8, 3-18 years of age), congenital (eg, chromosomal anomalies, OR > 2, 3-18 years of age), and mental disorders (eg, intellectual disability, OR > 1.7, 6-18 years of age). Novel comorbidities included endocrine metabolic diseases (eg, failure to thrive, OR = 2.5, ages 0-2), digestive disorders (gastroesophageal reflux disease: OR = 1.7, 6-11 years of age; and constipation: OR > 1.6, 3-11 years of age), and sense organs (strabismus: OR > 1.8, 3-18 years of age).DiscussionA multi-PheWAS intersection approach on real-world data as presented in this study uniquely contributes to the growing body of research regarding sex-based comorbidity analysis in ASD population.ConclusionsOur findings provide insights into female-enriched ASD comorbidities that are potentially important in diagnosis, as well as the identification of distinct comorbidity patterns influencing anticipatory treatment or referrals. The code is publicly available (https://github.com/hms-dbmi/sexDifferenceInASD).     

Demonstrating an approach for evaluating synthetic geospatial and temporal epidemiologic data utility: results from analyzing >1.8 million SARS-CoV-2 tests in the United States National COVID Cohort Collaborative (N3C)

ObjectiveThis study sought to evaluate whether synthetic data derived from a national coronavirus disease 2019 (COVID-19) dataset could be used for geospatial and temporal epidemic analyses.Materials and MethodsUsing an original dataset (n = 1 854 968 severe acute respiratory syndrome coronavirus 2 tests) and its synthetic derivative, we compared key indicators of COVID-19 community spread through analysis of aggregate and zip code-level epidemic curves, patient characteristics and outcomes, distribution of tests by zip code, and indicator counts stratified by month and zip code. Similarity between the data was statistically and qualitatively evaluated.ResultsIn general, synthetic data closely matched original data for epidemic curves, patient characteristics, and outcomes. Synthetic data suppressed labels of zip codes with few total tests (mean = 2.9 ± 2.4; max = 16 tests; 66% reduction of unique zip codes). Epidemic curves and monthly indicator counts were similar between synthetic and original data in a random sample of the most tested (top 1%; n = 171) and for all unsuppressed zip codes (n = 5819), respectively. In small sample sizes, synthetic data utility was notably decreased.DiscussionAnalyses on the population-level and of densely tested zip codes (which contained most of the data) were similar between original and synthetically derived datasets. Analyses of sparsely tested populations were less similar and had more data suppression.ConclusionIn general, synthetic data were successfully used to analyze geospatial and temporal trends. Analyses using small sample sizes or populations were limited, in part due to purposeful data label suppression—an attribute disclosure countermeasure. Users should consider data fitness for use in these cases.     

IGF2BP2 and obesity interaction analysis for type 2 diabetes mellitus in Chinese Han population

Background

The objective of this study was to systematically evaluate the contribution of the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) to type 2 diabetes mellitus (T2DM) and its interaction with obesity to T2DM susceptibility.

Methods

To clarify whether IGF2BP2 is an independent risk factor for T2DM in Chinese population, we conducted a study with a total of 2,301 Chinese Han subjects, including 1,166 T2DM patients and 1,135 controls, for the genotype of a most common and widely studied polymorphism—rs4402960 of IGF2BP2. Genotyping was performed by iPLEX technology. Gene and environment interaction analysis was performed by using multiple logistic regression models.

Results

The repeatedly confirmed association between IGF2BP2 (rs4402960) and T2DM had not been replicated in this cohort (P = 0.182). Interestingly, we found that obese subjects (body mass index (BMI) ≥ 28.0 kg/m²) bearing the minor A allele had an increased risk to develop T2DM (P = 0.008 for allele analysis and P < 0.001 for genotype analysis).

Conclusions

The present study provided data suggesting that the wild C allele of IGF2BP2 (rs4402960) had a protective effect against T2DM in obese subjects of Chinese Han population.