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Background The burden of spinal pain can be aggravated by the hazards of opioid analgesics, which are still widely prescribed for spinal pain despite evidence-based clinical guidelines that identify non-pharmacological therapies as the preferred first-line approach. Previous studies have found that chiropractic care is associated with decreased use of opioids, but have not focused on older Medicare beneficiaries, a vulnerable population with high rates of co-morbidity and polypharmacy. The purpose of this investigation was to evaluate the association between chiropractic utilization and use of prescription opioids among older adults with spinal pain. Methods We conducted a retrospective observational study in which we examined a nationally representative multi-year sample of Medicare claims data, 2012–2016. The study sample included 55,949 Medicare beneficiaries diagnosed with spinal pain, of whom 9,356 were recipients of chiropractic care and 46,593 were non-recipients. We measured the adjusted risk of filling a prescription for an opioid analgesic for up to 365 days following diagnosis of spinal pain. Using Cox proportional hazards modeling and inverse weighted propensity scoring to account for selection bias, we compared recipients of both primary care and chiropractic to recipients of primary care alone regarding the risk of filling a prescription. Results The adjusted risk of filling an opioid prescription within 365 days of initial visit was 56% lower among recipients of chiropractic care as compared to non-recipients (hazard ratio 0.44; 95% confidence interval 0.40–0.49). Conclusions Among older Medicare beneficiaries with spinal pain, use of chiropractic care is associated with significantly lower risk of filling an opioid prescription.

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 Diet is important for chronic disease management, with limited research understanding dietary choices among those with multi-morbidity, the state of having 2 or more chronic conditions. The objective of this study was to identify associations between packaged food and drink purchases and diet-related cardiometabolic multi-morbidity (DRCMM). Methods Cross-sectional associations between packaged food and drink purchases and household DRCMM were investigated using a national sample of U.S. households participating in a research marketing study. DRCMM households were defined as household head(s) self-reporting 2 or more diet-related chronic conditions. Separate multivariable logistic regression models were used to model the associations between household DRCMM status and total servings of, and total calories and nutrients from, packaged food and drinks purchased per month, as well as the nutrient density (protein, carbohydrates, and fat per serving) of packaged food and drinks purchased per month, adjusted for household size. Results Among eligible households, 3795 (16.8%) had DRCMM. On average, households with DRCMM versus without purchased 14.8 more servings per capita, per month, from packaged foods and drinks (p p = 0.002, p = 0.000, respectively). DRCMM households averaged fewer grams per serving of protein, carbohydrates, and fat per month across all food and drink purchases (all p p Conclusions DRCMM households purchased greater quantities of packaged food and drinks per capita than non-DRCMM households, which contributed to more fat, carbohydrates, and sodium in the home. However, food and drinks in DRCMM homes on average were lower in nutrient-density. Future studies are needed to understand the motivations for packaged food and drink choices among households with DRCMM to inform interventions targeting the home food environment.

Background Super-utilizers represent approximately 5% of the population in the United States (U.S.) and yet they are responsible for over 50% of healthcare expenditures. Using characteristics of hospital service areas (HSAs) to predict utilization of resource intensive healthcare (RIHC) may offer a novel and actionable tool for identifying super-utilizer segments in the population. Consumer expenditures may offer additional value in predicting RIHC beyond typical population characteristics alone. Methods Cross-sectional data from 2017 was extracted from 5 unique sources. The outcome was RIHC and included emergency room (ER) visits, inpatient days, and hospital expenditures, all expressed as log per capita. Candidate predictors from 4 broad groups were used, including demographics, adults and child health characteristics, community characteristics, and consumer expenditures. Candidate predictors were expressed as per capita or per capita percent and were aggregated from zip-codes to HSAs using weighed means. Machine learning approaches (Random Forrest, LASSO) selected important features from nearly 1,000 available candidate predictors and used them to generate 4 distinct models, including non-regularized and LASSO regression, random forest, and gradient boosting. Candidate predictors from the best performing models, for each outcome, were used as independent variables in multiple linear regression models. Relative contribution of variables from each candidate predictor group to regression model fit were calculated. Results The median ER visits per capita was 0.482 [IQR:0.351–0.646], the median inpatient days per capita was 0.395 [IQR:0.214–0.806], and the median hospital expenditures per capita was $2,302 [1$,544.70-$3,469.80]. Using 1,106 variables, the test-set coefficient of determination (R2) from the best performing models ranged between 0.184–0.782. The adjusted R2 values from multiple linear regression models ranged from 0.311–0.8293. Relative contribution of consumer expenditures to model fit ranged from 23.4–33.6%. Discussion Machine learning models predicted RIHC among HSAs using diverse population data, including novel consumer expenditures and provides an innovative tool to predict population-based healthcare utilization and expenditures. Geographic variation in utilization and spending were identified.

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.

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

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.

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.

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.

This study was a 12-week feasibility weight-loss intervention consisting of caloric restriction and aerobic/resistance exercise in older adults with obesity (body mass index ≥ 30kg/m(2)) in a geographically isolated area. Primary outcomes assessed weight and physical function. Mean age was 71.0±5.1years (67% female). Individuals completed 100% of all assessments, attended 88% of the physical therapy classes and 89% of the nutrition sessions. Level of satisfaction (5-point Likert) was high (5.0, 1 – low; 5 - high). Weight decreased from 93.7±9.7 to 89.4±4.0kg (p

OBJECTIVE: Body composition changes with aging can increase rates of obesity, frailty and impact function. Measuring adiposity using body fat (%BF) or central adiposity using waist circumference (WC) have greater diagnostic accuracy than traditional measures such as body mass index (BMI). DESIGN: This is an observational study SETTING: This study focused on older community-dwelling participants PARTICIPANTS: We identified individuals age ≥ 60 years old using the 1999–2004 cross-sectional National Health and Nutrition Survey (NHANES). INTERVENTION: The primary analysis evaluated the association between frailty and %BF or WC. Frailty was the primary predictor (robust=referent) and %BF and WC were considered continuous outcomes. Multiple imputation analyses accounted for missing characteristics. MEASUREMENT: Dual energy x-ray absorptiometry was used to assess %BF and WC was objectively measured. Frailty was defined using an adapted version of Fried’s criteria that was self-reported: (low BMI

Hospital readmission within 30 days is associated with higher risks of complications, death, and increased costs. Accurate statistical models to stratify the risk of 30-day readmission or death after cardiac surgery could help clinical teams focus care on those patients at highest risk. We hypothesized biomarkers could improve prediction for readmission or mortality.Levels of ST2, galectin-3, N-terminal pro-brain natriuretic peptide, cystatin C, interleukin-6, and interleukin-10 were measured in samples from 1,046 patients discharged after isolated coronary artery bypass graft surgery from eight medical centers, with external validation in 1,194 patients from five medical centers. Thirty-day readmission or mortality were ascertained using Medicare, state all-payer claims, and the National Death Index. We tested and externally validated the clinical models and the biomarker panels using area under the receiver-operating characteristics (AUROC) statistics.There were 112 patients (10.7%) who were readmitted or died within 30 days after coronary artery bypass graft surgery. The Society of Thoracic Surgeons augmented clinical model resulted in an AUROC of 0.66 (95% confidence interval: 0.61 to 0.71). The biomarker panel with The Society of Thoracic Surgeons augmented clinical model resulted in an AUROC of 0.74 (bootstrapped 95% confidence interval: 0.69 to 0.79, p0.0001). External validation of the model showed limited improvement with the addition of a biomarker panel, with an AUROC of 0.51 (95% confidence interval: 0.45 to 0.56).Although biomarkers significantly improved prediction of 30-day readmission or mortality in our derivation cohort, the external validation of the biomarker panel was poor. Biomarkers perform poorly, much like other efforts to improve prediction of readmission, suggesting there are many other factors yet to be explored to improve prediction of readmission.

A property and criticism of instrumental variable (IV) estimators are that they estimate the exposure effect in the compliers; individuals whose exposure is influenced by the instrument. It is conceivable that the exposure effect is different in individuals whose exposure is not influenced by the instrument. For that reason, it is useful to know who the compliers are. We present methods for reporting averages and other statistics, and comparing them between the compliers and non-compliers, which are applicable to scenarios in which the instrument and exposure are fixed in time and dichotomous. The methods are illustrated in a comparison of outcomes between teaching and nonteaching hospitals in patients undergoing brain or spinal surgery.

Background Novel cardiac biomarkers including soluble suppression of tumorigenicity 2, galectin-3, and the N-terminal prohormone of brain natriuretic peptide may be associated with long-term adverse outcomes after cardiac surgery. We sought to measure the association between cardiac biomarker levels and 1-year hospital readmission or mortality. Methods Plasma biomarkers from 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from 8 medical centers were measured in a cohort from the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. We evaluated the association between preoperative and postoperative biomarkers and 1-year readmission or mortality using Kaplan-Meier estimates and Cox proportional hazards modeling, adjusting for covariates used in The Society of Thoracic Surgeons 30-day readmission model. Results The median follow-up time was 365 days. After adjustment for established risk factors, above-median levels of postoperative galectin-3 (median 10.35 ng/mL; hazard ratio, 1.40; 95% confidence interval, 1.08 to 1.80; p = 0.010) and N-terminal prohormone of brain natriuretic peptide (median = 15.21 ng/mL, hazard ratio, 1.42; 95% confidence interval, 1.07 to 1.87; p = 0.014) were each significantly associated with 1-year readmission or mortality. Conclusions In patients undergoing cardiac surgery, novel cardiac biomarkers were associated with readmission or mortality independent of established risk factors. Measurement of these biomarkers may improve our ability to identify patients at highest risk for readmission or mortality before discharge. This will also allow resource allocation accordingly, while implementing strategies for personalized medicine based on the biomarker profile of the patient.

Proportional hazard Cox regression models are frequently used to analyze the impact of different factors on time-to-event outcomes. Most practitioners are familiar with and interpret research results in terms of hazard ratios. Direct differences in survival curves are, however, easier to understand for the general population of users and to visualize graphically. Analyzing the difference among the survival curves for the population at risk allows easy interpretation of the impact of a therapy over the follow-up. When the available information is obtained from observational studies, the observed results are potentially subject to a plethora of measured and unmeasured confounders. Although there are procedures to adjust survival curves for measured covariates, the case of unmeasured confounders has not yet been considered in the literature. In this article we provide a semi-parametric procedure for adjusting survival curves for measured and unmeasured confounders. The method augments our novel instrumental variable estimation method for survival time data in the presence of unmeasured confounding with a procedure for mapping estimates onto the survival probability and the expected survival time scales.

Background An increasing number of elderly patients with dementia are undergoing surgical operations. Little is known about the differential impact of dementia on surgical outcomes. We investigated whether demented patients undergoing surgical operations have worse outcomes than their non-demented counterparts. Methods We performed a cohort study of all patients undergoing a series of surgical operations who were registered in the New York Statewide Planning and Research Cooperative System (SPARCS) database from 2009 to 2013. We examined the association of dementia with inpatient case-fatality, discharge to a facility, and length of stay (LOS). Coarsened exact matching was used to balance comorbidities among the comparison groups, and mixed effect methods were used to control for clustering at the hospital level. Results During the study period, 342,075 patients underwent surgical operations that met the inclusion criteria. Multivariable logistic regression models, after coarsened exact matching, demonstrated that demented patients were not associated with higher case-fatality (OR, 0.43; 95% CI, 0.13–1.36), but were associated with higher rates of discharge to a facility (OR, 1.71; 95% CI, 1.26–2.31) and longer LOS (Adjusted difference, 31%; 95% CI, 26%–36%). These persisted in pre-specified subgroups stratified on particular operations. Conclusions Using a comprehensive all-payer cohort of surgical patients in New York State we identified an association of dementia with increased rate of discharge to rehabilitation and longer LOS. No difference was identified in the case fatality of the two groups. Policy makers, payers, and physicians should take these findings into account when designing new policies, and when counseling patients.

This diagnostic study evaluates the accuracy and assessment time of an artificial intelligence (AI)–augmented digital system compared with standard microscopic assessment for interpretation of slides with colorectal polyp samples., Key Points Question Can an artificial intelligence (AI)–augmented digital system improve classification accuracy of colorectal polyps by pathologists compared with standard microscopic assessment? Findings In this diagnostic study including 15 pathologists using microscopic examination and an AI-augmented digital system to interpret 100 slides with colorectal polyp samples, use of the AI-augmented digital system significantly improved pathologists' classification accuracy from 73.9% to 80.8% compared with standard microscopic assessment. Meaning These findings suggest that use of an AI-augmented digital system may be associated with improved treatment of patients with colorectal cancer and with improved follow-up surveillance planning to prevent subsequent cancer development., Importance Colorectal polyps are common, and their histopathologic classification is used in the planning of follow-up surveillance. Substantial variation has been observed in pathologists’ classification of colorectal polyps, and improved assessment by pathologists may be associated with reduced subsequent underuse and overuse of colonoscopy. Objective To compare standard microscopic assessment with an artificial intelligence (AI)–augmented digital system that annotates regions of interest within digitized polyp tissue and predicts polyp type using a deep learning model to assist pathologists in colorectal polyp classification. Design, Setting, and Participants In this diagnostic study conducted at a tertiary academic medical center and a community hospital in New Hampshire, 100 slides with colorectal polyp samples were read by 15 pathologists using a microscope and an AI-augmented digital system, with a washout period of at least 12 weeks between use of each modality. The study was conducted from February 10 to July 10, 2020. Main Outcomes and Measures Accuracy and time of evaluation were used to compare pathologists’ performance when a microscope was used with their performance when the AI-augmented digital system was used. Outcomes were compared using paired t tests and mixed-effects models. Results In assessments of 100 slides with colorectal polyp specimens, use of the AI-augmented digital system significantly improved pathologists' classification accuracy compared with microscopic assessment from 73.9% (95% CI, 71.7%-76.2%) to 80.8% (95% CI, 78.8%-82.8%) (P

Telomere shortening is associated with age and risk of medical comorbidity. We assessed the relationship between measures of adiposity, leukocyte telomere length, and mortality and whether it is modified by age. Subjects with dual-energy X-ray absorptiometry measures were identified using the National Health and Nutrition Examination Survey 1999–2002. Obesity was categorized using two body fat definitions (BF1%: men ⩾25%; females ⩾35%; BF2% ⩾28% and ⩾38%, respectively), body mass index (BMI) and waist circumference (WC; men ⩾102 cm; females ⩾88 cm). Telomere length relative to standard reference DNA (T/S ratio) was assessed using quantitative PCR. Weighted multivariable regression models evaluated the association of telomere length with adiposity, both continuously and categorically (low/normal BF%, low/high WC and standard BMI categories). Differences in telomere length by age and adiposity were ascertained and subsequent models were stratified by age. Proportional hazard models assessed the risk of mortality by adiposity status. A telomere by adiposity interaction was tested in the entire cohort and by age category (

To investigate the effect of exposure to a virtual reality (VR) environment preoperatively on patient-reported outcomes for surgical operations.There is a scarcity of well-developed quality improvement initiatives targeting patient satisfaction.We performed a randomized controlled trial of patients undergoing cranial and spinal operations in a tertiary referral center. Patients underwent a 1:1 randomization to an immersive preoperative VR experience or standard preoperative experience stratified on type of operation. The primary outcome measures were the Evaluation du Vecu de l'Anesthesie Generale (EVAN-G) score and the Amsterdam Preoperative Anxiety and Information (APAIS) score, as markers of the patient's experience during the surgical encounter.During the study period, a total of 127 patients (mean age 55.3 years, 41.9% females) underwent randomization. The average EVAN-G score was 84.3 (standard deviation, SD, 6.4) after VR, and 64.3 (SD, 11.7) after standard preoperative experience (difference, 20.0; 95% confidence interval, CI, 16.6-23.3). Exposure to an immersive VR experience also led to higher APAIS score (difference, 29.9; 95% CI, 24.5-35.2). In addition, VR led to lower preoperative VAS stress score (difference, -41.7; 95% CI, -33.1 to -50.2), and higher preoperative VAS preparedness (difference, 32.4; 95% CI, 24.9-39.8), and VAS satisfaction (difference, 33.2; 95% CI, 25.4-41.0) scores. No association was identified with VAS stress score (difference, -1.6; 95% CI, -13.4 to 10.2).In a randomized controlled trial, we demonstrated that patients exposed to preoperative VR had increased satisfaction during the surgical encounter. Harnessing the power of this technology, hospitals can create an immersive environment that minimizes stress, and enhances the perioperative experience.

OBJECTIVE The comparative effectiveness of the 2 treatment options—surgical clipping and endovascular coiling—for unruptured cerebral aneurysms remains an issue of debate and has not been studied in clinical trials. The authors investigated the association between treatment method for unruptured cerebral aneurysms and outcomes in elderly patients. METHODS The authors performed a cohort study of 100% of Medicare fee-for-service claims data for elderly patients who had treatment for unruptured cerebral aneurysms between 2007 and 2012. To control for measured confounding, the authors used propensity score conditioning and inverse probability weighting with mixed effects to account for clustering at the level of the hospital referral region (HRR). An instrumental variable (regional rates of coiling) analysis was used to control for unmeasured confounding and to create pseudo-randomization on the treatment method. RESULTS During the study period, 8705 patients underwent treatment for unruptured cerebral aneurysms and met the study inclusion criteria. Of these patients, 2585 (29.7%) had surgical clipping and 6120 (70.3%) had endovascular coiling. Instrumental variable analysis demonstrated no difference between coiling and clipping in 1-year postoperative mortality (OR 1.25, 95% CI 0.68–2.31) or 90-day readmission rate (OR 1.04, 95% CI 0.66–1.62). However, clipping was associated with a greater likelihood of discharge to rehabilitation (OR 6.39, 95% CI 3.85–10.59) and 3.6 days longer length of stay (LOS; 95% CI 2.90–4.71). The same associations were present in propensity score–adjusted and inverse probability–weighted models. CONCLUSIONS In a cohort of Medicare patients, there was no difference in mortality and the readmission rate between clipping and coiling of unruptured cerebral aneurysms. Clipping was associated with a higher rate of discharge to a rehabilitation facility and a longer LOS.

Background & Aims There is debate over the type of electrosurgical setting that should be used for polyp resection. Some endoscopists use a type of blended current (yellow), whereas others prefer coagulation (blue). We performed a single-blinded, randomized trial to determine whether type of electrosurgical setting affects risk of adverse events or recurrence. Methods Patients undergoing endoscopic mucosal resection of nonpedunculated colorectal polyps 20 mm or larger (n = 928) were randomly assigned, in a 2 × 2 design, to groups that received clip closure or no clip closure of the resection defect (primary intervention) and then to either a blended current (Endocut Q) or coagulation current (forced coagulation) (Erbe Inc) (secondary intervention and focus of the study). The study was performed at multiple centers, from April 2013 through October 2017. Patients were evaluated 30 days after the procedure (n = 919), and 675 patients underwent a surveillance colonoscopy at a median of 6 months after the procedure. The primary outcome was any severe adverse event in a per patient analysis. Secondary outcomes were complete resection and recurrence at first surveillance colonoscopy in a per polyp analysis. Results Serious adverse events occurred in 7.2% of patients in the Endocut group and 7.9% of patients in the forced coagulation group, with no significant differences in the occurrence of types of events. There were no significant differences between groups in proportions of polyps that were completely removed (96% in the Endocut group vs 95% in the forced coagulation group) or the proportion of polyps found to have recurred at surveillance colonoscopy (17% and 17%, respectively). Procedural characteristics were comparable, except that 17% of patients in the Endocut group had immediate bleeding that required an intervention, compared with 11% in the forced coagulation group (P = .006). Conclusions In a randomized trial to compare 2 commonly used electrosurgical settings for the resection of large colorectal polyps (Endocut vs forced coagulation), we found no difference in risk of serious adverse events, complete resection rate, or polyp recurrence. Electrosurgical settings can therefore be selected based on endoscopist expertise and preference. Clinicaltrials.gov ID NCT01936948.

Background Limited data exist to describe factors that influence the use of different endovascular treatments for peripheral arterial disease. Therefore, we studied sex differences in the utilization of endovascular treatment modalities and their impact on arterial patency. Methods and Results We analyzed procedures from 2010 to 2016 in the Vascular Quality Initiative for arteries treated with percutaneous transluminal angioplasty (PTA) alone, stenting (with/without PTA), and atherectomy (with/without PTA). We explored sex differences in treatment modality by arterial segment (iliac, femoropopliteal, and tibial) with multivariable logistic regression. We used Kaplan–Meier survival analysis and multivariable Cox regression to study sex differences in arterial reintervention and occlusion. In this cohort, patients (n=58 247, mean age 68 years, 41% women,) had 106 073 arteries treated (median=2 arteries, interquartile range=1–3). Half (50%) of these arteries were treated with stents, 39% with PTA alone, and 11% with atherectomy. After risk adjustment, women were less likely to undergo stenting or atherectomy (versus PTA alone) in the femoropopliteal (stent risk ratio=0.78 [0.74–0.82]; atherectomy risk ratio=0.69 [0.58–0.82]) and tibial arteries (stent risk ratio=0.70 [0.55–0.89]; atherectomy risk ratio=0.87 [0.70–1.07]). In the iliac arteries there was no sex difference in stenting, and atherectomy was rarely used (0.2%). Women underwent reintervention in the femoropopliteal arteries (hazard ratio=1.28 [1.17–1.40]) or developed an occlusion in the iliac (hazard ratio=1.42 [1.12–1.81]) and femoropopliteal arteries (hazard ratio=1.19 [1.06–1.34]) more frequently than men. Conclusions Women were less likely to undergo stenting or atherectomy and had higher rates of occlusion and reintervention, especially in the femoropopliteal arteries. Evidence‐based guidelines are needed to guide optimal use of endovascular treatments for men and women., See Editorial Braun and Kougias

Previous work from our group indicated an association between the gastrointestinal microbiota of infants with cystic fibrosis (CF) and airway disease in this population. Here we report that stool microbiota of infants with CF demonstrates an altered but largely unchanging within-individual bacterial diversity (alpha diversity) over the first year of life, in contrast to the infants without CF (control cohort), which showed the expected increase in alpha diversity over the first year. The beta diversity, or between-sample diversity, of these two cohorts was significantly different over the first year of life and was statistically significantly associated with airway exacerbations, confirming our earlier findings. Compared with control infants, infants with CF had reduced levels of Bacteroides, a bacterial genus associated with immune modulation, as early as 6 weeks of life, and this significant reduction of Bacteroides spp. in the cohort with CF persisted over the entire first year of life. Only two other genera were significantly different across the first year of life: Roseburia was significantly reduced and Veillonella was significantly increased. Other genera showed differences between the two cohorts but only at selected time points. In vitro studies demonstrated that exposure of the apical face of polarized intestinal cell lines to Bacteroides species supernatants significantly reduced production of interleukin 8 (IL-8), suggesting a mechanism whereby changes in the intestinal microbiota could impact inflammation in CF. This work further establishes an association between gastrointestinal microbiota, inflammation, and airway disease in infants with CF and presents a potential opportunity for therapeutic interventions beginning in early life. IMPORTANCE There is growing evidence for a link between gastrointestinal bacterial communities and airway disease progression in CF. We demonstrate that infants with CF ≤1 year of age show a distinct stool microbiota versus that of control infants of a comparable age. We detected associations between the gut microbiome and airway exacerbation events in the cohort of infants with CF, and in vitro studies provided one possible mechanism for this observation. These data clarify that current therapeutics do not establish in infants with CF a gastrointestinal microbiota like that in healthy infants, and we suggest that interventions that direct the gastrointestinal microbiota closer to a healthy state may provide systemic benefits to these patients during a critical window of immune programming that might have implications for lifelong health.

Objective:To evaluate the association between novel pre- and post-operative biomarker levels and 30-day unplanned readmission or mortality after paediatric congenital heart surgery.Methods:Children aged 18 years or younger undergoing congenital heart surgery (n = 162) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Collected novel pre- and post-operative biomarkers include soluble suppression of tumorgenicity 2, galectin-3, N-terminal prohormone of brain natriuretic peptide, and glial fibrillary acidic protein. A model based on clinical variables from the Society of Thoracic Surgery database was developed and evaluated against two augmented models.Results:Unplanned readmission or mortality within 30 days of cardiac surgery occurred among 21 (13%) children. The clinical model augmented with pre-operative biomarkers demonstrated a statistically significant improvement over the clinical model alone with a receiver-operating characteristics curve of 0.754 (95% confidence interval: 0.65–0.86) compared to 0.617 (95% confidence interval: 0.47–0.76; p-value: 0.012). The clinical model augmented with pre- and post-operative biomarkers demonstrated a significant improvement over the clinical model alone, with a receiver-operating characteristics curve of 0.802 (95% confidence interval: 0.72–0.89; p-value: 0.003).Conclusions:Novel biomarkers add significant predictive value when assessing the likelihood of unplanned readmission or mortality after paediatric congenital heart surgery. Further exploration of the utility of these novel biomarkers during the pre- or post-operative period to identify early risk of mortality or readmission will aid in determining the clinical utility and application of these biomarkers into routine risk assessment.

Cardiac surgery results in a multifactorial systemic inflammatory response with inflammatory cytokines, such as interleukin-10 and 6 (IL-10 and IL-6), shown to have potential in the prediction of adverse outcomes including readmission or mortality. This study sought to measure the association between IL-6 and IL-10 levels and 1-year hospital readmission or mortality following cardiac surgery. Plasma biomarkers IL-6 and IL-10 were measured in 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from eight medical centers participating in the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. Readmission status and mortality were ascertained using Medicare, state all-payer claims, and the National Death Index. We evaluated the association between preoperative and postoperative cytokines and 1-year readmission or mortality using Kaplan–Meier estimates and Cox’s proportional hazards modeling, adjusting for covariates used in the Society of Thoracic Surgeons 30-day readmission model. The median follow-up time was 1 year. After adjustment, patients in the highest tertile of postoperative IL-6 values had a significantly increased risk of readmission or death within 1 year (HR: 1.38; 95% CI: 1.03–1.85), and an increased risk of death within 1 year of discharge (HR: 4.88; 95% CI: 1.26–18.85) compared with patients in the lowest tertile. However, postoperative IL-10 levels, although increasing through tertiles, were not found to be significantly associated independently with 1-year readmission or mortality (HR: 1.25; 95% CI: .93–1.69). Pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 may be postoperative markers of cardiac injury, and IL-6, specifically, shows promise in predicting readmission and mortality following cardiac surgery.

Background & Aims Bleeding is the most common severe complication after endoscopic mucosal resection of large colon polyps and is associated with significant morbidity and cost. We examined whether prophylactic closure of the mucosal defect with hemoclips after polyp resection reduces the risk of bleeding. Methods We performed a multicenter, randomized trial of patients with a large nonpedunculated colon polyp (≥20 mm) at 18 medical centers in North America and Spain from April 2013 through October 2017. Patients were randomly assigned to groups that underwent endoscopic closure with a clip (clip group) or no closure (control group) and followed. The primary outcome, postprocedure bleeding, was defined as a severe bleeding event that required hospitalization, a blood transfusion, colonoscopy, surgery, or another invasive intervention within 30 days after completion of the colonoscopy. Subgroup analyses included postprocedure bleeding with polyp location, polyp size, or use of periprocedural antithrombotic medications. We also examined the risk of any serious adverse event. Results A total of 919 patients were randomly assigned to groups and completed follow-up. Postprocedure bleeding occurred in 3.5% of patients in the clip group and 7.1% in the control group (absolute risk difference [ARD] 3.6%; 95% confidence interval [CI] 0.7%–6.5%). Among 615 patients (66.9%) with a proximal large polyp, the risk of bleeding in the clip group was 3.3% and in the control group was 9.6% (ARD 6.3%; 95% CI 2.5%–10.1%); among patients with a distal large polyp, the risks were 4.0% in the clip group and 1.4% in the control group (ARD –2.6%; 95% CI –6.3% to –1.1%). The effect of clip closure was independent of antithrombotic medications or polyp size. Serious adverse events occurred in 4.8% of patients in the clip group and 9.5% of patients in the control group (ARD 4.6%; 95% CI 1.3%–8.0%). Conclusions In a randomized trial, we found that endoscopic clip closure of the mucosal defect following resection of large colon polyps reduces risk of postprocedure bleeding. The protective effect appeared to be restricted to large polyps located in the proximal colon. ClinicalTrials.gov no: NCT01936948.

The impact of scope of practice of providers (predominantly adult versus predominantly pediatric) on the outcomes of cerebrovascular procedures in children remains an issue of debate. We investigated the association of scope of practice with the outcomes of cerebrovascular interventions.We performed a cohort study of all pediatric patients (younger than 18 years old) who underwent cerebrovascular procedures from 2009 to 2013 and were registered in the Statewide Planning and Research Cooperative System (SPARCS) database. In order to control for confounding, we used propensity score conditioning and mixed effects analysis to account for clustering at the hospital level.During the study period, there were 1243 pediatric patients who underwent cerebrovascular procedures and met the inclusion criteria. Of these, 631 (50.7 %) underwent treatment by providers with predominantly adult practices and 612 (49.3 %) by physicians who operated predominantly on children. The mixed-effects multivariable regression analysis demonstrated lack of association of predominantly adult practice with inpatient mortality (OR, 1.20; 95 % CI, 0.61-2.38), discharge to a facility (OR, 1.50; 95 % CI, 0.73-3.09), and length of stay (LOS) (adjusted difference, 0.003; 95 % CI, -0.09 to 0.10). These associations persisted in propensity-adjusted models.In a cohort of pediatric patients undergoing cerebrovascular procedures from a comprehensive all-payer database, we did not demonstrate a difference in mortality, discharge to a facility, and LOS between providers with predominantly adult and predominantly pediatric practices.

The Foundation for the National Institutes of Health Sarcopenia Project validated cutpoints for appendicular lean mass (ALM) to identify individuals with functional impairment. We hypothesized that the prevalence of sarcopenia and sarcopenic obesity would be similar based on the different Foundation for the National Institutes of Health criteria, increase with age, and be associated with risk of impairment limitations. We identified 4984 subjects at least 60 years of age from the National Health and Nutrition Examination Surveys 1999-2004. Sarcopenia was defined using ALM (men19.75 kg, women15.02 kg) and ALM adjusted for body mass index (BMI; men0.789 kg/m2, women0.512 kg/m2). Sarcopenic obesity is defined as subjects fulfilling the criteria for sarcopenia and obesity by body fat (men ≥25%, women ≥35%). Prevalence rates of both sarcopenia and sarcopenic obesity were evaluated with respect to sex, age category (60-69, 70-79, and80 years) and race. We assessed the association of physical limitations, basic and instrumental activities of daily living and sarcopenia status. The mean age was 70.5 years in men and 71.6 years in women. Half (50.8%; n = 2531) were female, and mean BMI was 28 kg/m2 in both sexes. Appendicular lean mass was higher in men than in women (24.1 vs. 16.3; P.001), but fat mass was lower (30.9 vs. 42.0; P.001). In men, sarcopenia prevalence was 16.0% and 27.8% using the ALM and ALM/BMI criteria. In women, prevalence was 40.5% and 19.3% using the ALM and ALM/BMI criteria. Sarcopenia was associated with a 1.10 (0.86-1.41) and 0.93 (0.74-1.16), and 1.46 (1.10-1.94), and 2.13 (1.41-3.20) risk of physical limitations using the ALM and ALM/BMI definitions in men and women, respectively. Prevalence of sarcopenia and sarcopenic obesity varies greatly, and a uniform definition is needed to identify and characterize these high-risk populations.

PurposeTo assess the association of low- vs. guideline-recommended high-intensity cystoscopic surveillance with outcomes among patients with high-risk non-muscle invasive bladder cancer (NMIBC).Materials & methodsA retrospective cohort study of Veterans Affairs patients diagnosed with high-risk NMIBC between 2005 and 2011 with follow-up through 2014. Patients were categorized by number of surveillance cystoscopies over two years following diagnosis: low- (1-5) vs. high-intensity (6 or more) surveillance. Propensity score adjusted regression models were used to assess the association of low-intensity cystoscopic surveillance with frequency of transurethral resections, and risk of progression to invasive disease and bladder cancer death.ResultsAmong 1,542 patients, 520 (33.7%) underwent low-intensity cystoscopic surveillance. Patients undergoing low-intensity surveillance had fewer transurethral resections (37 vs. 99 per 100 person-years; pConclusionsPatients with high-risk NMIBC undergoing low- vs. high-intensity cystoscopic surveillance underwent fewer transurethral resections, but did not experience an increased risk of progression or bladder cancer death. These findings provide a strong rationale for a clinical trial to determine whether low-intensity surveillance is comparable to high-intensity surveillance for cancer control in high-risk NMIBC.

RATIONALE: Cognitive impairment is one of the most common complaints for persons with epilepsy (PWE). These impairments are not only associated with seizures, but are also regularly reported as adverse effects of antiepileptic drugs (AEDs). Previous studies have examined cognitive effects of both AED monotherapy and polytherapy, yet there is limited research on these differences with respect to both subjective and objective cognition. The current study uses data from previous research conducted by the Centers for Disease Control and Prevention (CDC)-sponsored Managing Epilepsy Well (MEW) Network collaborative. We used three distinct archival datasets from the following: (1) the HOBSCOTCH efficacy trial at Dartmouth-Hitchcock Medical Center (HOB-1), (2) the multisite replication trial (HOB-2), and (3) epilepsy self-management research conducted at the NYU School of Medicine. METHODS: This retrospective analysis combined baseline data from three datasets to determine how the number of AEDs and the type of AEDs were associated with subjective (patient-reported) and objective (examiner-assessed) cognition. Subjective cognition was captured using the cognitive subscale of the Quality of Life in Epilepsy Inventory (QOLIE-31) in all three datasets (n = 224), while objective cognition was measured using the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) in the HOB-1 dataset (n = 65) and the Brief Test of Adult Cognition by Telephone (BTACT) in the HOB-2 dataset (n = 91). Multivariable linear regression was utilized for our initial assessments, followed by propensity score matching to provide stronger control of covariates. Matching was based on significantly different covariates, such as education, depression, and history of prior epilepsy surgery. Nonparametric statistical tests were utilized to compare these matched subjects. RESULTS: Subjective cognitive impairment was significantly worse among individuals on polytherapy (2 + AEDs) compared with those on monotherapy (1 AED) (adjusted p = 0.041). These findings were consistent with our propensity score matched comparison of monotherapy and polytherapy, which indicated that polytherapy was associated with worse overall subjective cognition (adjusted p = 0.01), in addition to impairments on the RBANS (Total score p = 0.05) and specific subdomains of the BTACT (Episodic Verbal Memory p < 0.01, Working Memory p < 0.01, Processing Speed p < 0.01). Interestingly, older generation AEDs were associated with better language performance than newer generation and combined generation AED therapy (RBANS Language p = 0.03). These language-specific findings remained significant after controlling for the effects of topiramate and zonisamide (p = 0.04). CONCLUSIONS: A greater number of AEDs is significantly and negatively associated with subjective and objective cognition in PWE, and is in line with previous research. Antiepileptic drug type did not, in itself, appear to be associated with subjective cognition. Our findings suggest that ineffective AEDs should be replaced, rather than introducing additional AEDs to a treatment regimen. Further, while subjective and objective cognition assessments were both sensitive at detecting differences based on AED status, the neuropsychological objective subdomains offer additional and specific insights into how cognition is impaired with AEDs.

BACKGROUND: Self-reported weight change may lead to adverse outcomes. We evaluated weight change with cutpoints of low lean mass (LLM) in older adults. METHODS: Of 4,984 subjects ≥60 years from NHANES 1999-2004, we applied LLM cutoffs of appendicular lean mass (ALM):body mass index (BMI) males

Background Previous research suggests that novel biomarkers may be used to identify patients at increased risk of acute kidney injury following cardiac surgery. The purpose of this study was to evaluate the relationship between preoperative levels of circulating Galectin-3 (Gal-3) and acute kidney injury after cardiac surgery. Methods Preoperative serum Gal-3 was measured in 1498 patients who underwent coronary artery bypass graft (CABG) surgery and/or valve surgery as part of the Northern New England Biomarker Study between 2004 and 2007. Preoperative Gal-3 levels were measured using multiplex assays and grouped into terciles. Univariate and multinomial logistic regression was used to assess the predictive ability of Gal-3 terciles and AKI occurrence and severity. Results Before adjustment, patients in the highest tercile of Gal-3 had a 2.86-greater odds of developing postoperative KDIGO Stage 2 or 3 (p

Background The emergent disposition of acute stroke patients remains an issue of debate. We investigated whether a hub-and-spoke model was associated with worse stroke outcomes when compared to care exclusively in comprehensive centers. Methods We performed a cohort study of all acute ischemic stroke patients who were hospitalized in endovascular-capable facilities, and were registered in the New York Statewide Planning and Research Cooperative System (SPARCS) database from 2009 to 2015. We examined the association of transfer status (transfer to endovascular capable hospitals versus initial treatment in these facilities) with inpatient case-fatality, discharge to a facility, and length of stay (LOS). An instrumental variable analysis was used to control for unmeasured confounding and simulate a randomized trial. Results During the study period, 128,122 acute stroke patients met inclusion criteria. Instrumental variable analysis demonstrated that patients transferred to endovascular-capable hospitals did not have higher case-fatality (Adjusted difference, 4.4%; 95% CI, −0.1% to 9.0%), rate discharge to a facility (Adjusted difference, −2.3%; 95% CI, −5.2% to 0.6%), or longer LOS (Adjusted difference, 4.2; 95% CI, −2.2 to 10.1) in comparison to patients presenting for initial treatment in these facilities. The same associations were present when restricting the cohort to patients receiving intravenous tissue plasminogen (IV-tPA) and to patients receiving mechanical thrombectomy. Conclusions Using a comprehensive all-payer cohort of acute ischemic stroke patients in New York State we demonstrated that patients treated in a hub-and-spoke model were not associated with worse outcomes than patients receiving care exclusively in comprehensive institutions. This needs to be taken into consideration when considering acute emergency services in this setting.

Sarcopenia is a gradual loss of muscle mass and strength that occurs with aging. This muscle deterioration is linked to increased morbidity, disability, and other adverse outcomes. Although reduced handgrip strength can be considered a marker of sarcopenia and other aging-related decline in the elderly, there is limited research on this physical health problem in at-risk groups with common biopsychosocial conditions such as depression. Our primary objective was to ascertain level of combined handgrip strength and its relationship with depression among adults aged 60 years and older. Unadjusted and adjusted linear regression models were conducted with a cross-sectional survey dataset. Secondary dataset from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Community-dwelling, noninstitutionalized adults ≥60 years old (n=3,421). The predictor variables included a positive screen for clinically relevant depression (referent=PHQ-9 score

Background Galectin-3 (Gal-3) is a well-established biomarker of adverse clinical outcomes, but its prognostic value for long-term survival after cardiac surgery is not well understood. Elevated levels of Gal-3 have been found to be remarkably associated with higher risk of death in both acute decompensated and chronic heart failure populations. Its prognostic value for long-term survival after cardiac surgery is not known. Methods A sample of patients contributing to the Northern New England Cardiovascular Disease Study Group Cardiac Surgery Registry from 2004 to 2007 were enrolled in a prospective biomarker cohort (N = 1690). Preoperative Gal-3 levels were measured and categorized by quartile. We used Kaplan-Meier survival analysis and Cox regression models, adjusting for variables in The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategy probability calculator to evaluate the association between elevated Gal-3 levels and survival to 6 years. Results Preoperative Gal-3 levels ranged from 1.72 to 28.89 ng/mL (mean, 8.96 ng/mL; median, 8.06 ng/mL; interquartile range, 5.42-11.08 ng/mL). Crude survival decreased by increasing quartile. After adjustment, serum levels of Gal-3 in the highest quartile of the cohort were associated with significantly decreased survival compared with the lowest quartile (hazard ratio [HR] 2.22; 95% confidence interval [CI], 1.40-3.54; P = .001). No decrease in survival was found for the middle quartiles (HR 1.36; 95% CI, 0.87-2.12; P = .177). Conclusions A substantial association was found between elevated preoperative Gal-3 levels and risk of mortality after isolated coronary artery bypass grafting surgery. An assessment of the relationship between preoperative serum biomarkers and long-term survival can be used for risk stratification or estimating postsurgical prognosis.

Key Points Question Can a novel instrumental variable method designed for time-dependent outcomes more accurately determine the relative long-term mortality after carotid endarterectomy vs carotid artery stenting? Findings In this registry-based, multicenter cohort study of 86 017 patients, the hazard ratio of long-term mortality for carotid endarterectomy vs carotid artery stenting was 0.83 (95% CI, 0.70-0.98) using instrumental variable analysis, compared with 0.69 (95% CI, 0.65-0.74) using a traditional Cox regression model. Meaning Results from this instrumental variable method show that the survival advantage conferred by carotid endarterectomy is more modest than suggested by traditional adjustment methods, aligning with results from randomized clinical trials., Importance Choosing between competing treatment options is difficult for patients and clinicians when results from randomized and observational studies are discordant. Observational real-world studies yield more generalizable evidence for decision making than randomized clinical trials, but unmeasured confounding, especially in time-to-event analyses, can limit validity. Objectives To compare long-term survival after carotid endarterectomy (CEA) and carotid artery stenting (CAS) in real-world practice using a novel instrumental variable method designed for time-to-event outcomes, and to compare the results with traditional risk-adjustment models used in observational research for survival analyses. Design, Setting, and Participants A multicenter cohort study was performed. The Vascular Quality Initiative, an observational quality improvement registry, was used to compare long-term mortality after CEA vs CAS. The study included 86 017 patients who underwent CEA (n = 73 312) or CAS (n = 12 705) between January 1, 2003, and December 31, 2016. Patients were followed up for long-term mortality assessment by linking the registry data to Medicare claims. Medicare claims data were available through September 31, 2015. Exposure Procedure type (CEA vs CAS). Main Outcomes and Measures The hazard ratios (HRs) of all-cause mortality using unadjusted, adjusted, propensity-matched, and instrumental variable methods were examined. The instrumental variable was the proportion of CEA among the total carotid procedures (endarterectomy and stenting) performed at each hospital in the 12 months before each patient’s index operation and therefore varies over the study period. Results Participants who underwent CEA had a mean (SD) age of 70.3 (9.4) years compared with 69.1 (10.4) years for CAS, and most were men (44 191 [60.4%] for CEA and 8117 [63.9%] for CAS). The observed 5-year mortality was 12.8% (95% CI, 12.5%-13.2%) for CEA and 17.0% (95% CI, 16.0%-18.1%) for CAS. The unadjusted HR of mortality for CEA vs CAS was 0.67 (95% CI, 0.64-0.71), and Cox-adjusted and propensity-matched HRs were similar (0.69; 95% CI, 0.65-0.74 and 0.71; 95% CI, 0.65-0.77, respectively). These findings are comparable with published observational studies of CEA vs CAS. However, the association between CEA and mortality was more modest when estimated by instrumental variable analysis (HR, 0.83; 95% CI, 0.70-0.98), a finding similar to data reported in randomized clinical trials. Conclusions and Relevance The study found a survival advantage associated with CEA over CAS in unadjusted and Cox-adjusted analyses. However, this finding was more modest when using an instrumental variable method designed for time-to-event outcomes for risk adjustment. The instrumental variable-based results were more similar to findings from randomized clinical trials, suggesting this method may provide less biased estimates of time-dependent outcomes in observational analyses., This registry-based multicenter cohort study examines long-term survival after carotid endarterectomy (CEA) and carotid artery stenting (CAS) in real-world practice using a novel instrumental variable method designed for time-to-event outcomes compared with traditional risk-adjustment models used in observational studies for survival analyses.