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CCR Translation for This Article from MicroRNA-10b Expression Correlates with Response to Neoadjuvant Therapy and Survival in Pancreatic Ductal Adenocarcinoma

ObjectiveEctopic fat deposition within and around organs is a stronger predictor of cardiometabolic disease status than body mass index. Fat deposition within the lymphatic system is poorly understood. This study examined the association between the prevalence of cardiometabolic disease and ectopic fat deposition within axillary lymph nodes (LNs) visualized on screening mammograms.MethodsA cross-sectional study was conducted on 834 women presenting for full-field digital screening mammography. The status of fat-infiltrated LNs was assessed based on the size and morphology of axillary LNs from screening mammograms. The prevalence of cardiometabolic disease was retrieved from the electronic medical records, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, high blood glucose, cardiovascular disease, stroke, and non-alcoholic fatty liver disease.ResultsFat-infiltrated axillary LNs were associated with a high prevalence of T2DM among all women (adjusted odds ratio: 3.92, 95% CI: [2.40, 6.60], p-value < 0.001) and in subgroups of women with and without obesity. Utilizing the status of fatty LNs improved the classification of T2DM status in addition to age and BMI (1.4% improvement in the area under the receiver operating characteristic curve).ConclusionFat-infiltrated axillary LNs visualized on screening mammograms were associated with the prevalence of T2DM. If further validated, fat-infiltrated axillary LNs may represent a novel imaging biomarker of T2DM in women undergoing screening mammography.

Mendelian randomization (MR) is an application of instrumental variable (IV) methods to observational data in which the IV is a genetic variant. MR methods applicable to the general exponential family of distributions are currently not well characterized. We adapt a general linear model framework to the IV setting and propose a general MR method applicable to any full-rank distribution from the exponential family. Empirical bias and coverage are estimated via simulations. The proposed method is compared to several existing MR methods. Real data analyses are performed using data from the REGARDS study to estimate the potential causal effect of smoking frequency on stroke risk in African Americans. In simulations with binary variates and very weak instruments the proposed method had the lowest median [Q1 , Q3 ] bias (0.10 [-3.68 to 3.62]); compared with 2SPS (0.27 [-3.74 to 4.26]) and the Wald method (-0.69 [-1.72 to 0.35]). Low bias was observed throughout other simulation scenarios; as well as more than 90% coverage for the proposed method. In simulations with count variates, the proposed method performed comparably to 2SPS; the Wald method maintained the most consistent low bias; and 2SRI was biased towards the null. Real data analyses find no evidence for a causal effect of smoking frequency on stroke risk. The proposed MR method has low bias and acceptable coverage across a wide range of distributional scenarios and instrument strengths; and provides a more parsimonious framework for asymptotic hypothesis testing compared to existing two-stage procedures.

Background and Aims: Higher adenoma detection rates reduce the risk of postcolonoscopy colorectal cancer (PCCRC). Clinically significant serrated polyps (CSSPs; defined as any sessile serrated polyp, traditional serrated adenoma, large [≥1 cm] or proximal hyperplastic polyp >5 mm) also lead to PCCRC, but there are no data on associated CSSP detection rates (CSSDRs). We used data from the New Hampshire Colonoscopy Registry (NHCR) to investigate the association between PCCRC risk and endoscopist CSSDR. Methods: We included NHCR patients with 1 or more follow-up events: either a colonoscopy or a colorectal cancer (CRC) diagnosis identified through linkage with the New Hampshire State Cancer Registry. We defined our outcome, PCCRC, in 3 time periods: CRC diagnosed 6 to 36 months, 6 to 60 months, or all examinations (6 months or longer) after an index examination. We excluded patients with CRC diagnosed at or within 6 months of the index examination, with incomplete examinations, or with inflammatory bowel disease. The exposure variable was endoscopist CSSDR at the index colonoscopy. Cox regression was used to model the hazard of PCCRC on CSSDR controlling for age, sex, index findings, year of examination, personal history of colorectal neoplasia, and having more than 1 surveillance examination. Results: One hundred twenty-eight patients with CRC diagnosed at least 6 months after their index examination were included. Our cohort included 142 endoscopists (92 gastroenterologists). We observed that the risk for PCCRC 6 months or longer after the index examination was significantly lower for examinations performed by endoscopists with CSSDRs of 3% to

Background Cervical artery dissection and subsequent ischemic stroke is the most serious safety concern associated with cervical spinal manipulation. Methods We evaluated the association between cervical spinal manipulation and cervical artery dissection among older Medicare beneficiaries in the United States. We employed case-control and case-crossover designs in the analysis of claims data for individuals aged 65+, continuously enrolled in Medicare Part A (covering hospitalizations) and Part B (covering outpatient encounters) for at least two consecutive years during 2007–2015. The primary exposure was cervical spinal manipulation; the secondary exposure was a clinical encounter for evaluation and management for neck pain or headache. We created a 3-level categorical variable, (1) any cervical spinal manipulation, 2) evaluation and management but no cervical spinal manipulation and (3) neither cervical spinal manipulation nor evaluation and management. The primary outcomes were occurrence of cervical artery dissection, either (1) vertebral artery dissection or (2) carotid artery dissection. The cases had a new primary diagnosis on at least one inpatient hospital claim or primary/secondary diagnosis for outpatient claims on at least two separate days. Cases were compared to 3 different control groups: (1) matched population controls having at least one claim in the same year as the case; (2) ischemic stroke controls without cervical artery dissection; and (3) case-crossover analysis comparing cases to themselves in the time period 6–7 months prior to their cervical artery dissection. We made each comparison across three different time frames: up to (1) 7 days; (2) 14 days; and (3) 30 days prior to index event. Results The odds of cervical spinal manipulation versus evaluation and management did not significantly differ between vertebral artery dissection cases and any of the control groups at any of the timepoints (ORs 0.84 to 1.88; p > 0.05). Results for carotid artery dissection cases were similar. Conclusion Among Medicare beneficiaries aged 65 and older who received cervical spinal manipulation, the risk of cervical artery dissection is no greater than that among control groups.

Introduction: Congenital heart defects (CHD) are the most common birth defects and are estimated to affect almost 1% of births per year in the US. Most CHD prevalence estimates are based on data from population-based birth defects surveillance systems and these estimates are inconsistent due to varied definitions. It is therefore important to derive high-quality, population-based estimates of the prevalence of CHD to help care for this vulnerable population. Methods: We analyzed all payer claims data (APCD) from Colorado from 2012-2019. Children with CHD were identified by applying CHD ICD-9 and ICD-10 diagnoses codes from the Society of Thoracic Surgeons (STS) International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD) harmonized cardiac codes. We included children with CHD < 18 years of age who resided in Colorado, had a documented zip code, and had at least one ambulatory healthcare claim. We analyzed the test for linear trends in the proportion of CHD diagnoses from 2012-2019 with the Cochran-Armitage (Z) test. Differences among patient characteristics and CHD diagnosis were tested using the Pearson Chi-square test and Wilcoxon rank sum tests as appropriate. Results: Overall the current study analyzed 1,565,438 children with 36,567 CHD diagnoses (i.e. 23.4 per 1,000 live births), comprising 2.3% of the pediatric population. Between 2012 and 2019 the statewide rate of children diagnosed with CHD significantly increased from 21.9 to 32.3 per 1,000 children per year (Z: 5.38; p Conclusion: The current study is the first population-level analysis of pediatric CHD in the US and these findings suggest that the statewide CHD prevalence rate has increased significantly since 2012. Children with CHD are a priority population for quality improvement in pediatrics given their growing prevalence and corresponding risk of adverse outcomes.

Background SRL172 prevented disease due to Mycobacterium tuberculosis in a Phase 3 trial. DAR-901 represents a scalable manufacturing process for SRL172. We sought to determine if DAR-901 would prevent infection with M. tuberculosis among BCG-primed adolescents age 13–15 years in Tanzania. Methods Adolescents with a negative T- SPOT.TBR interferon gamma release assay (IGRA) were randomized 1:1 to three intradermal injections of DAR-901 or saline placebo at 0, 2 and 4 months. Repeat IGRAs were performed at 2 months, and at 1, 2, and 3 years. The primary efficacy outcome was time to new TB infection (IGRA conversion to positive); the secondary outcome was time to persistent TB infection (IGRA conversion with repeat positive IGRA). Results Among 936 participants screened 667 were eligible and randomized to their first dose of vaccine or placebo (safety cohort). At 2 months, 625 participants remained IGRA-negative and were scheduled for the additional two doses (efficacy cohort). DAR-901 was safe and well-tolerated. One DAR-901 recipient developed a vaccine site abscess. Neither the primary nor secondary endpoints differed between the two treatment arms (p = 0.90 and p = 0.20, respectively). DAR-901 IGRA converters had median responses to ESAT-6 of 50.1 spot-forming cells (SFCs) vs. 19.6 SFCs in placebo IGRA converters (p = 0.03). Conclusions A three-dose series of 1 mg DAR-901 was safe and well-tolerated but did not prevent initial or persistent IGRA conversion. DAR-901 recipients with IGRA conversion demonstrated enhanced immune responses to ESAT-6. Since protection against disease may require different immunologic responses than protection against infection a trial of DAR-901 to prevent TB disease is warranted. Trial Registration. The trial is registered at ClinicalTrials.gov as NCT02712424.

Cardiac biomarkers soluble ST-2 (sST-2) and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) may be associated with long-term survival after cardiac surgery. This study explored the relationship between long-term survival after cardiac surgery and serum biomarker levels.Patients undergoing cardiac surgery from 2004 to 2007 were enrolled in a prospective biomarker cohort in the Northern New England Cardiovascular Disease Study Group Registry. Preoperative serum biomarker levels, postoperative serum biomarker levels, and the change in serum biomarker levels were categorized by quartile. The study used Kaplan-Meier survival analysis and Cox regression models adjusted for variables in the American College of Cardiology Foundation-Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategy (ASCERT) long-term survival calculator to study the association of biomarker levels with long-term survival. After Kaplan-Meier analysis, quartiles 2 and 3 were found to have similar survival and were therefore combined into 1 category.In the study cohort (n = 1648), median follow-up time was 8.5 years (interquartile range, 7.6-9.7 years), during which there were 227 deaths. The 10-year survival rate was 86%. Kaplan-Meier survival analysis demonstrated a significant (P.001) difference across quartiles of each biomarker level measurement. After adjustment, preoperative levels, postoperative levels, and the change in biomarker levels in quartile 4 (highest serum levels or change) were significantly predictive of worse survival (hazard ratio range, 1.77-2.89; all P.05) compared with quartile 1; however, levels of sST-2 and NT-proBNP in quartiles 2 and 3 demonstrated a nonstatistically significant trend with long-term survival.Elevated preoperative and postoperative levels of sST-2 or NT-proBNP and large changes in these biomarkers' levels are associated with an increased risk of worse survival after cardiac surgery. These biomarkers can be used for risk stratification or assessing postsurgical prognosis.

Serrated polyps are important colorectal cancer precursors and are most commonly located in the proximal colon, where post-polypectomy bleeding rates are higher. There is limited clinical trial evidence to guide best practices for resection of large serrated polyps (LSPs).In a multicenter trial, patients with large (≥20 mm) non-pedunculated polyps undergoing endoscopic mucosal resection (EMR) were randomized to clipping of the resection base or no clipping. This analysis is stratified by histologic subtype of study polyp(s), categorized as serrated [sessile serrated lesions (SSLs) or hyperplastic polyps (HPs)] or adenomatous, comparing clip vs control groups. The primary outcome was severe post-procedure bleeding within 30 days of colonoscopy.A total of 179 participants with 199 LSPs (191 SSLs and 8 HPs) and 730 participants with 771 adenomatous polyps were included in the study. Overall, 5 patients with LSPs (2.8%) experienced post-procedure bleeding compared with 42 (5.8%) of those with adenomas. There was no difference in post-procedure bleeding rates between patients in the clip vs control group among those with LSPs (2.3% vs 3.3%, respectively, difference 1.0%; P = NS). However, among those with adenomatous polyps, clipping was associated with a lower risk of post-procedure bleeding (3.9% vs 7.6%, difference 3.7%; P = .03) and overall serious adverse events (5.5% vs 10.6%, difference 5.1%; P = .01).The post-procedure bleeding risk for LSPs removed via EMR is low, and there is no discernable benefit of prophylactic clipping of the resection base in this group. This study indicates that the benefit of endoscopic clipping following EMR may be specific for2 cm adenomatous polyps located in the proximal colon.gov, Number: NCT01936948.

Background Sepsis remains a leading cause of death among inpatients. Scoring systems designed to identify inpatients with sepsis currently have limited effectiveness. This single institution, retrospective, case-control study aims to improve sepsis decision support tool performance using temporal analyses of sepsis-specific and general deterioration scoring systems. Methods Sequential Organ Failure Assessment, National Early Warning Scores (NEWS), and Modified Early Warning Scores were calculated using four years of inpatient data. Sensitivity and specificity analyses compared performance of each score, calculated as a function of both various score cut-off values and time before sepsis diagnosis using established proxies for identifying clinical suspicion for sepsis. Results NEWS had the best sensitivity-specificity performance (AUROC 82.7) when examining various score cutoffs and time intervals during which diagnosis criteria were met. Comparison of false positives/negatives with various score thresholds showed a low rate of false positives with a NEWS of 7. Score trends in the hours leading up to sepsis criteria being met showed a marked increase for the sepsis group while for the cases there was a decrease during a comparable period. Conclusions Temporal analyses of scores for patients coded as having sepsis provides novel insights into patterns of deterioration. The methods and results provide practical details demonstrating how general deterioration algorithms can be used to alert trained responders to potential cases of sepsis to improve sepsis recognition and treatment opportunities.

Purpose: Bendamustine and rituximab (BR) has been established as a superior frontline therapy over R-CHOP in the treatment of follicular lymphoma (FL). Yttrium-90 Ibritumomab tiuxetan (90YIT) is an effective consolidation strategy after chemotherapy induction. This prospective, single-arm, multicenter, phase II trial evaluated the response rate, progression-free survival (PFS), and tolerability of BR followed by consolidation with 90YIT in patients with untreated FL. Patients and Methods: The study included grade 1 to 3a FL patients aged ≥18 years, chemotherapy-naïve, and requiring treatment for stage II–IV disease. Study treatment included an initial rituximab treatment, followed by four cycles of BR. Patients were eligible for consolidation with 90YIT, 6 to 12 weeks after BR, if they obtained at least a partial response after induction had adequate count recovery and bone marrow infiltration < 25%. Results: Thirty-nine patients were treated. Eighty-two percent had an intermediate or high-risk Follicular Lymphoma International Prognostic Index score, and 6 of 39 (15%) were grade 3a. The response rate was 94.8%, and the complete response(CR)/CR unconfirmed (CRu) rate was 77% in the intention-to-treat analysis. The conversion rate from PR to CR/Cru after 90YIT was 81%. After median follow-up of 45 months, the PFS was 0.71 (95% confidence interval, 0.57–0.89). Conclusions: This report demonstrates that four cycles of BR followed by consolidation with 90YIT achieve high response rates that are durable. In addition, consolidation with 90YIT results in a high conversion rate of PR to CR/CRu. A short course of BR followed by 90YIT is a safe and effective regimen for frontline treatment of FL.

INTRODUCTION: Fast food (FF) advertising is a potential risk factor for FF consumption among children, yet the impact of such advertising on children’s FF intake has not been assessed in a longitudinal, naturalistic study. Whether parents’ FF consumption mitigates advertising effects is also unknown. METHODS: One-year, longitudinal study among 624 preschool-age children, 3–5 years old, and one parent each recruited from New Hampshire, 2014–2015. Parents completed six online surveys every eight weeks and, at each, reported the number of times their children consumed FF in the past week. Each child’s advertisement exposure was determined by counting the brand-specific FF advertisements aired within the programs they viewed on children’s TV networks during the study. At baseline, parents reported the frequency of their own FF consumption. Data were analyzed in 2017–2018. RESULTS: Three FF brands targeted TV advertising to children during the study: McDonald’s, Wendy’s and Subway. Few children were exposed to child-targeted advertising for Wendy’s or Subway. Results from adjusted Poisson regression models focused on McDonald’s showed a differential effect of advertisement exposure on children’s McDonald’s intake in the past week (any or mean intake) by parental FF consumption (P

BACKGROUND: Surveillance recommendations for patients with low-risk non-muscle-invasive bladder cancer (NMIBC) are based on limited evidence. Our objective was to add to the evidence by assessing outcomes after frequent versus recommended cystoscopic surveillance. METHODS: This is a retrospective cohort study of patients diagnosed with low-risk (low grade Ta) NMIBC from 2005 – 2011 with follow-up through 2014 from the Department of Veterans Affairs. Patients were classified as having undergone frequent versus recommended cystoscopic surveillance (>3 versus 1–3 cystoscopies in the first 2 years after diagnosis). Using propensity score adjusted models, we estimated the impact of frequent cystoscopy on the number of transurethral resections, the number of resections without cancer in the specimen, and on risk of progression to muscle-invasive cancer or bladder cancer death. RESULTS: Among 1,042 patients, 798 (77%) had more frequent cystoscopy than recommended. In adjusted analyses, the frequent cystoscopy group had twice as many transurethral resections (55 versus 26 per 100 person years; p

Summary Two-stage instrumental variable methods are commonly used for estimating average causal effects in the presence of an unmeasured confounder. In the context of the proportional hazard Cox regression models, this problem has recently received attention with several methods being proposed. Previously, we developed an improved estimator under the incumbent two-stage residual inclusion procedure called ‘2SRI’ by adding a Gaussian frailty in the second stage. We now consider the more complex situation in which the treatment and the unmeasured confounders can have time varying effects, illustrating the method with the case of a step function with one prespecified change point. We prove that, in situations where the effects of the unmeasured confounder or the treatment change during the follow-up, the first stage of the 2SRI algorithm induces a frailty with time varying coefficients in the second stage, which enables incumbent methods and our previously developed procedure to be improved on. A Monte Carlo simulation study demonstrates the superior performance of the proposed extension of 2SRI that we develop. We apply the new procedure to estimate the effect of endarterectomy versus carotid artery stenting on the time to death of patients suffering from carotid artery disease by using linked vascular quality initiative registry–Medicare data.

Clinical monitoring systems have been implemented in the inpatient hospital setting for decades, with little attention given to systems analysis or assessment of impact on clinician workflow or patient care. This study provides an example of how system-level design and analysis can be applied in this domain, with specific focus on early detection of patient deterioration to mitigate failure to rescue events. Wireless patient sensors and pulse oximetry-based surveillance system monitors with advanced display and information systems capabilities were introduced to 71 general care beds in two units. Nursing workflow was redesigned to integrate use of the new system and its features into patient assessment activities. Patient characteristics, vital sign documentation, monitor alarm, workflow, and system utilization data were collected and analyzed for the period five months before and five months after implementation. Comparison unit data were also collected and analyzed for the same periods. A survey pertaining to staff satisfaction and system performance was administered after implementation. Statistical analysis was performed to examine differences in the before and after data for the target and control units. The enhanced monitoring system received high staff satisfaction ratings and significantly improved key clinical elements related to early recognition of changes in patient state, including reducing average vital signs data collection time by 28%, increasing patient monitoring time (rate ratio 1.22), and availability and accuracy of patient information. Impact on clinical alarms was mixed, with no significant increase in clinical alarms per monitored hour.

OBJECTIVES: Soluble suppression of tumorgenicity 2 (sST2) biomarker is an emerging predictor of adverse clinical outcomes, but its prognostic value for in-hospital mortality after coronary artery bypass grafting (CABG) is not well understood. This study measured the association between operative sST2 levels and in-hospital mortality after CABG. METHODS: A prospective cohort of 1,560 CABG patients were analysed from the Northern New England Cardiovascular Disease Study Group Biomarker Study. The primary outcome was in-hospital mortality after CABG surgery (n=32). RESULTS: After risk adjustment, patients in the third tercile of pre-, post- and pre-to-postoperative sST2 values experienced significantly greater odds of in-hospital death compared to patients in the first tercile of sST2 values. The addition of both postoperative and pre-to-postoperative sST2 biomarker significantly improved ability to predict in-hospital mortality status following CABG surgery, compared to using the EuroSCORE II mortality model alone, (c-statistic: 0.83 [95% CI: 0.75, 0.92], p-value 0.0213) and (c-statistic: 0.83 [95% CI: 0.75, 0.92], p-value 0.0215), respectively. CONCLUSION: sST2 values are associated with in-hospital mortality after CABG surgery and postoperative and pre-to-post operative sST2 values improve prediction. Our findings suggest that sST2 can be used as a biomarker to identify adult patients at greatest risk of in-hospital death after CABG surgery.

Objective: A 5% change in weight is a significant predictor for frailty and obesity. We ascertained how self-reported weight change over the lifespan impacts rates of frailty in older adults. Methods: We identified 4,984 subjects ≥60 years with body composition measures from the National Health and Nutrition Examination Survey. An adapted version of Fried’s frailty criteria was used as the primary outcome. Self-reported weight was assessed at time current,1 and 10 years earlier and at age 25. Weight changes between each time point were categorized as ≥ 5%, ≤5% or neutral. Logistic regression assessed the impact of weight change on the outcome of frailty. Results: Among 4,984 participants, 56.5% were female, mean age was 71.1 years, and mean BMI was 28.2kg/m2. A weight loss of ≥ 5% had a higher association with frailty compared to current weight, age 25 (OR 2.94 [1.72,5.02]), 10 years ago (OR 1.68 [1.05,2.69]), and 1 year ago (OR 1.55 [1.02,2.36]). Weight gain in the last year was associated with increased rate of frailty (1.59 [1.09,2.32]). Conclusion: There is an association between frailty and reported weight loss over time while only weight gain in the last year has an association with frailty.

Objectives To measure the association between statin exposure and mortality in lung cancer patients belonging to different categories of histological subtype. Materials and methods A cohort of 19,974 individuals with incident lung cancer between 2007 and 2011 was identified using the SEER-Medicare linked database. Statin exposure both pre- and post-diagnosis was analyzed to identify a possible association with cancer-specific mortality in patients stratified by histological subtype. Intention-to-treat analyses and time-dependent Cox regression models were used to calculate hazard ratios and 95% confidence intervals (95% CIs) corresponding to statin exposure both pre- and post-diagnosis, respectively. Results Overall baseline statin exposure was associated with a decrease in mortality risk for squamous-cell carcinoma patients (HR = 0.89, 95% CI = 0.82–0.96) and adenocarcinoma patients (HR = 0.87, 95% CI = 0.82–0.94), but not among those with small-cell lung cancer. Post-diagnostic statin exposure was associated with prolonged survival in squamous-cell carcinoma patients (HR = 0.68, 95% CI = 0.59–0.79) and adenocarcinoma patients (HR = 0.78, 95% CI = 0.68–0.89) in a dose-dependent manner. Conclusion There is consistent evidence indicating that baseline or post-diagnostic exposure to simvastatin and atorvastatin is associated with extended survival in non-small-cell lung cancer subtypes. These results warrant further randomized clinical trials to evaluate subtype-specific effects of certain statins in patient cohorts with characteristics similar to those examined in this study.

Purpose Surgical excision is currently recommended for all occurrences of atypical ductal hyperplasia (ADH) found on core needle biopsies for malignancy diagnoses and treatment of lesions. The excision of all ADH lesions may lead to overtreatment, which results in invasive surgeries for benign lesions in many women. A machine learning method to predict ADH upgrade may help clinicians and patients decide whether combined active surveillance and hormonal therapy is a reasonable alternative to surgical excision. Methods The following six machine learning models were developed to predict ADH upgrade from core needle biopsy: gradient-boosting trees, random forest, radial support vector machine (SVM), weighted K-nearest neighbors (KNN), logistic elastic net, and logistic regression. The study cohort consisted of 128 lesions from 124 women at a tertiary academic care center in New Hampshire who had ADH on core needle biopsy and who underwent an associated surgical excision from 2011 to 2017. Results The best-performing models were gradient-boosting trees (area under the curve [AUC], 68%; accuracy, 78%) and random forest (AUC, 67%; accuracy, 77%). The top five most important features that determined ADH upgrade were age at biopsy, lesion size, number of biopsies, needle gauge, and personal and family history of breast cancer. Using the random forest model, 98% of all malignancies would have been diagnosed through surgical biopsies, whereas 16% of unnecessary surgeries on benign lesions could have been avoided (ie, 87% sensitivity at 45% specificity). Conclusion These results add to the growing body of support for machine learning models as useful aids for clinicians and patients in decisions about the clinical management of ADH.

The objective of this study was to compare patients' perspectives on the use of spinal manipulative therapy (SMT) compared to prescription drug therapy (PDT) with regard to health-related quality of life (HRQoL), patient beliefs, and satisfaction with treatment.Four cohorts of Medicare beneficiaries were assembled according to previous treatment received as evidenced in claims data: SMT, PDT, and 2 crossover cohorts (where participants experienced both types of treatments). A total of 195 Medicare beneficiaries responded to the survey. Outcome measures used were a 0-to-10 numeric rating scale to measure satisfaction, the Low Back Pain Treatment Beliefs Questionnaire to measure patient beliefs, and the 12-item Short Form Health Survey to measure HRQoL.Recipients of SMT were more likely to be very satisfied with their care (84%) than recipients of PDT (50%; P = .002). The SMT cohort self-reported significantly higher HRQoL compared to the PDT cohort; mean differences in physical and mental health scores on the 12-item Short Form Health Survey were 12.85 and 9.92, respectively. The SMT cohort had a lower degree of concern regarding chiropractic care for their back pain compared to the PDT cohort's reported concern about PDT (P = .03).Among older Medicare beneficiaries with chronic low back pain, long-term recipients of SMT had higher self-reported rates of HRQoL and greater satisfaction with their modality of care than long-term recipients of PDT. Participants who had longer-term management of care were more likely to have positive attitudes and beliefs toward the mode of care they received.

OBJECTIVES: The purpose of this study was to compare Medicare healthcare expenditures for patients who received long-term treatment of chronic low back pain (cLBP) with either opioid analgesic therapy (OAT) or spinal manipulative therapy (SMT). METHODS: We conducted a retrospective observational study using a cohort design for analysis of Medicare claims data. The study population included Medicare beneficiaries enrolled under Medicare Parts A, B, and D from 2012 through 2016. We assembled cohorts of patients who received long-term management of cLBP with OAT or SMT (such as delivered by chiropractic or osteopathic practitioners) and evaluated the comparative effect of OAT vs SMT upon expenditures, using multivariable regression to control for beneficiary characteristics and measures of health status, and propensity score weighting and binning to account for selection bias. RESULTS: The study sample totaled 28,160 subjects, of whom 77% initiated long-term care of cLBP with OAT, and 23% initiated care with SMT. For care of low back pain specifically, average long-term costs for patients who initiated care with OAT were 58% lower than those who initiated care with SMT. However, overall long-term healthcare expenditures under Medicare were 1.87 times higher for patients who initiated care via OAT as compared to those initiated care with SMT (95% CI 1.65-2.11; p

Background and study aim Delayed bleeding is a common adverse event following endoscopic mucosal resection (EMR) of large colorectal polyps. Prophylactic clip closure of the mucosal defect after EMR of nonpedunculated polyps larger than 20 mm reduces the incidence of severe delayed bleeding, especially in proximal polyps. This study aimed to evaluate factors associated with complete prophylactic clip closure of the mucosal defect after EMR of large polyps. Methods This is a post hoc analysis of the CLIP study (NCT01936948). All patients randomized to the clip group were included. Main outcome was complete clip closure of the mucosal resection defect. The defect was considered completely closed when no remaining mucosal defect was visible and clips were less than 1 cm apart. Factors associated with complete closure were evaluated in multivariable analysis. Results In total, 458 patients (age 65, 58 % men) with 494 large polyps were included. Complete clip closure of the resection defect was achieved for 338 polyps (68.4 %); closure was not complete for 156 (31.6 %). Factors associated with complete closure in adjusted analysis were smaller polyp size (odds ratio 1.06 for every millimeter decrease [95 % confidence interval 1.02–1.08]), good access (OR 3.58 [1.94–9.59]), complete submucosal lifting (OR 2.28 [1.36–3.90]), en bloc resection (OR 5.75 [1.48–22.39]), and serrated histology (OR 2.74 [1.35–5.56]). Conclusions Complete clip closure was not achieved for almost one in three resected large nonpedunculated polyps. While stable access and en bloc resection facilitate clip closure, most factors associated with clip closure are not modifiable. This highlights the need for alternative closure options and measures to prevent bleeding.

Supplemental Digital Content is available in the text., Background and Purpose: The impact of coronavirus disease 2019 (COVID-19) on the occurrence of ischemic stroke has been the subject of increased speculation but has not been confirmed in large observational studies. We investigated the association between COVID-19 and stroke. Methods: We performed a cross-sectional study involving patients discharged from a healthcare system in New York State, from January to April 2020. A mixed-effects logistic regression analysis and a propensity score–weighted analysis were used to control for confounders and investigate the association of COVID-19 with ischemic stroke. Similar techniques were used to detect the impact of concurrent COVID-19 infection on unfavorable outcomes for patients with stroke. Results: Among 24 808 discharges, 2513 (10.1%) were diagnosed with COVID-19, and 566 (0.2%) presented with acute ischemic stroke. Patients diagnosed with COVID-19 were at one-quarter the odds of stroke compared with other patients (odds ratio, 0.25 [95% CI, 0.16–0.40]). This association was consistent in all age groups. Our results were robust in sensitivity analyses, including propensity score–weighted regression models. In patients presenting with stroke, concurrent infection with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was associated with higher case-fatality (odds ratio, 10.50 [95% CI, 3.54–31.18]) and a trend towards increased occurrence of discharge to rehabilitation (odds ratio, 2.45 [95% CI, 0.81–1.25]). Conclusions: Using a comprehensive cross-section of patients from a large NY-based healthcare system, we did not identify a positive association between ischemic stroke and COVID-19. However, patients with stroke with COVID-19 had worse outcomes compared with those without, with over a 9-fold increase in mortality. Although no definitive conclusions can be reached from our observational study, our data do not support the concerns for an epidemic of stroke in young adults with COVID-19.

Background Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset. Methods To demonstrate efficacy, we evaluated this method on two simulation data sets to estimate the type I error rate and power. Simulations showed that ES-MDR identified interactions using less computational workload and allowed for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs = 108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data. Results Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR 1.24, P = 3.15 × 10–15), as the top marker to predict age of lung cancer onset. Conclusions From the results of our extensive simulations and analysis of a large GWAS study, we demonstrated that our method is an efficient algorithm that identified genetic interactions to include in our models to predict survival outcomes.

Identifying patient characteristics that influence the rate of colorectal polyp recurrence can provide important insights into which patients are at higher risk for recurrence. We used natural language processing to extract polyp morphological characteristics from 953 polyp-presenting patients’ electronic medical records. We used subsequent colonoscopy reports to examine how the time to polyp recurrence (731 patients experienced recurrence) is influenced by these characteristics as well as anthropometric features using Kaplan-Meier curves, Cox proportional hazards modeling, and random survival forest models. We found that the rate of recurrence differed significantly by polyp size, number, and location and patient smoking status. Additionally, right-sided colon polyps increased recurrence risk by 30% compared to left-sided polyps. History of tobacco use increased polyp recurrence risk by 20% compared to never-users. A random survival forest model showed an AUC of 0.65 and identified several other predictive variables, which can inform development of personalized polyp surveillance plans.

Background Older persons with obesity aged 65+ residing in rural areas have reduced access to weight management programs due to geographic isolation. The ability to integrate technology into health promotion interventions shows a potential to reach this underserved population. Methods A 12-week pilot in 28 older rural adults with obesity (body mass index [BMI] ≥ 30 kg/m2) was conducted at a community aging center. The intervention consisted of individualized, weekly dietitian visits focusing on behavior therapy and caloric restriction with twice weekly physical therapist-led group strengthening training classes in a community-based aging center. All participants were provided a Fitbit Flex 2. An aerobic activity prescription outside the strength training classes was provided. Results Mean age was 72.9 ± 5.3 years (82% female). Baseline BMI was 37.1 kg/m2, and waist circumference was 120.0 ± 33.0 cm. Mean weight loss (pre/post) was 4.6 ± 3.2 kg (4.9 ± 3.4%; p < .001). Of the 40 eligible participants, 33 (75%) enrolled, and the completion rate was high (84.8%). Objective measures of physical function improved at follow-up: 6-minute walk test improved: 35.7 ± 41.2 m (p < .001); gait speed improved: 0.10 ± 0.24 m/s (p = .04); and five-times sit-to-stand improved by 2.1 seconds (p < .001). Subjective measures of late-life function improved (5.2 ± 7.1 points, p = .003), as did Patient-Reported Outcome Measurement Information Systems mental and physical health scores (5.0 ± 5.7 and 4.4 ± 5.0, both p < .001). Participants wore their Fitbit 93.9% of all intervention days, and were overall satisfied with the trial (4.5/5.0, 1–5 low–high) and with Fitbit (4.0/5.0). Conclusions A multicomponent obesity intervention incorporating a wearable device is feasible and acceptable to older adults with obesity, and potentially holds promise in enhancing health.

Sex-based differences exist in the prevalence and clinical presentation of abdominal aortic aneurysm (AAA). However, it is unclear if sex is associated with AAA repair type and long-term mortality.To investigate whether a sex-related difference exists in mortality risk after AAA repair owing to differences in repair type.This cohort study uses data from the Vascular Quality Initiative, a national clinical registry, and Medicare claims to investigate endovascular and surgical repair procedures performed between January 1, 2003, and September 30, 2015, in patients aged 65 years or older with AAA. The data were analyzed from October 1, 2018, to November 19, 2019.Sex of the patient.Endovascular (EVR) or open surgical AAA repair type and subsequent long-term, all-cause mortality.In this cohort study of 16 386 patients, 12 757 (77.9%) were men and 3629 (22.1%) were women. Women were more likely than men to be older (mean [SD] age, 77 [6.5] years vs 75 [6.6] years; P .001), active smokers (33% vs 28%; P .001), and to have smaller aneurysms (mean [SD] diameter, 57 [11.7] mm vs 59 [17.7] mm; P .001). Surgical AAA repair was performed in 27% (983 of 3629) of women compared with 18% (2328 of 12 757) of men (P .001). After inverse probability weighting for risk adjustment, women were more likely to receive open surgical repair than EVR repair (risk ratio, 1.65; 95% CI, 1.51-1.80). The 10-year unadjusted survival rate after EVR repair was 14% lower in women than in men (23% vs 37%; log-rank P .001), but the rates were comparable after open surgical repair (36% in men vs 32% in women; log-rank P = .22). Risk-adjusted analysis showed that women were associated with higher mortality rates after EVR repair (hazard ratio, 1.13; 95% CI, 1.03-1.24), whereas both men and women had a similar risk of death after open surgical repair (hazard ratio, 0.94; 95% CI, 0.84-1.06). After further stratification by symptom severity, higher risk of mortality among women was limited to elective EVR and open surgical repair for ruptured AAA.In this study, women were 65% more likely than men to undergo open surgical repair. After EVR repair, women were 13% more likely to die than men, although no sex-based difference in mortality was found after open surgical repair. The differential treatment benefit of EVR repair in women is concerning given the shift toward an EVR-first approach to AAA repair.