Faculty Bibliography
Searched for:
department:Medicine. General Internal Medicine
recentyears:2
Total Results:
14850
Setting the Stage for the Next Phase of Social Determinants of Health Research [Editorial]
PMID: 35446609
ISSN: 1541-0048
CID: 5218482
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
PMCID:9005347
PMID: 35379992
ISSN: 1546-1718
CID: 5213092
Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature
PURPOSE/OBJECTIVE:The 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive [ER+], human epidermal growth factor receptor 2-negative [HER2-]) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer. METHODS:Neoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy. Pathologic complete response (pCR) and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed in 477 patients with IHC-defined ER+, HER2- tumors and in a reference group of 229 patients with IHC-defined triple-negative breast cancer (TNBC). RESULTS:< .001) tumors. The 5-year DMFS (%, [95% CI]) was significantly lower for patients with ER+/Basal tumors (66% [52.6 to 77.3]), compared with those with ER+/Luminal A tumors (92.3% [85.2 to 96.1]) and ER+/Luminal B tumors (73.5% [44.5 to 79.3]). Importantly, patients with ER+/Basal or TNBC/Basal tumors that had a pCR exhibited significantly improved DMFS and OS compared with those with residual disease. By contrast, patients with ER+/Luminal B tumors had comparable 5-year DMFS and OS whether or not they achieved pCR. CONCLUSION/CONCLUSIONS:Significant differences in chemosensitivity and 5-year outcome suggest patients with ER+/Basal molecular subtype may benefit from neoadjuvant regimens optimized for patients with TNBC/Basal tumors compared with patients with ER+/Luminal subtype. These data highlight the importance of identifying this subset of patients to improve treatment planning and long-term survival.
PMID: 35476550
ISSN: 2473-4284
CID: 5210342
Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals
We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.
PMCID:9005349
PMID: 35361970
ISSN: 1546-1718
CID: 5210182
Effect of Technology-Assisted Brief Abstinence Game on Long-term Smoking Cessation in Individuals Not Yet Ready to Quit: A Randomized Clinical Trial
IMPORTANCE/OBJECTIVE:Most trials of behavioral or pharmaceutical interventions for people who smoke are limited to individuals reporting they are ready to quit smoking. Engaging individuals who initially report they are not yet ready to quit in brief, precessation, skills-building interventions (eg, practice quit attempts or nicotine replacement therapy [NRT] sampling) is challenging. OBJECTIVE:To test an integrated behavioral plus NRT-sampling intervention using a gamification approach supported by mobile health. DESIGN, SETTING, AND PARTICIPANTS/METHODS:A multisite randomized clinical trial with site-level 1-to-1 allocation into 2 conditions was conducted in 4 US health care systems. A total of 433 individuals who were currently smoking and reported at enrollment that they were not ready to quit smoking were enrolled. The study was conducted from November 7, 2016, to July 31, 2020. INTERVENTIONS/METHODS:Take a Break (TAB) was a 3-week game experience and included 5 behavioral components (motivational messaging, challenge quizzes, brief abstinence goal setting, mobile health apps for cravings management, and reward points for participation) integrated with NRT sampling. TAB draws on social cognitive theory and game mechanics concepts to engage participants in health behavior change. The comparison included NRT sampling only. MAIN OUTCOMES AND MEASURES/METHODS:Time to first quit attempt (duration from TAB experience to primary outcome) and carbon monoxide level-verified smoking cessation at 6-month follow-up. All analyses used an intention-to-treat approach. RESULTS:Of the 433 individuals included in the trial, 223 were women (52%); mean (SD) age was 54 (13) years. More than half (53% [112 of 213]) of the TAB participants completed 100% of the daily challenge quizzes in the first week, 73% (145 of 199) of participants who completed the goal-setting call set a brief abstinence goal (most frequently 1-2 days of abstinence from cigarettes), and 75% (159 of 213) of participants used the mobile health apps to manage nicotine cravings. Time to the first quit attempt was lower for the TAB vs comparison group (hazard ratio, 1.68; 95% CI, 1.09-2.60; P = .02). At the 6-month follow-up, 18% (28 of 160) of TAB participants and 10% (17 of 171) of the comparison (χ2 test, P = .045) participants obtained carbon monoxide level-verified smoking cessation (accounting for clustering of outcomes by site; odds ratio, 1.92; 95% CI, 1.01-3.68; P = .048). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:The findings of this randomized clinical trial demonstrate that individuals not yet ready to quit smoking could be engaged in a brief abstinence game. Six months later, the TAB group had nearly double the rate of smoking cessation vs the NRT sampling comparison group. Integrating a skills-building game experience with brief NRT sampling can enhance long-term cessation among those not yet ready to quit smoking. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Identifier: NCT02973425.
PMCID:8787683
PMID: 35072714
ISSN: 2168-6114
CID: 5209932
Comparative Efficacy of Endoscopic Assist Devices on Colonic Adenoma Detection: A Systematic Review With Network Meta-analysis
BACKGROUND AND AIMS/OBJECTIVE:Numerous endoscopic assist devices exist, yet data surrounding their comparative efficacy is lacking. We conducted a systematic review with network meta-analysis to determine the comparative efficacy of endoscopic assist devices on colonic adenoma detection. METHODS:A systematic search was performed using multiple electronic databases through July 2020, to identify all randomized controlled trials and dual-arm observational studies compared with either other endoscopic assist devices and/or standard colonoscopy. The primary outcome was adenoma detection rate (ADR). Secondary outcomes included polyp detection rate (PDR), serrated adenoma detection rate (SADR), right-sided adenoma detection rate (RADR), and proximal adenoma detection rate (PADR). RESULTS:Fifty-seven studies (31,051 patients) met inclusion criteria and were analyzed. Network meta-analysis identified an enhanced ADR among (clear) cap [odds ratio (OR): 2.69, 95% confidence interval (CI): 1.45-4.99], endocuff, (OR: 4.95, 95% CI: 3.15-7.78), and endoring (OR: 3.68, 95% CI: 1.47-9.20)-with no significant difference amongst any particular device. Similar findings for PDR were also seen. Enhanced SADR was identified for endocuff (OR: 9.43) and endoring (OR: 4.06) compared with standard colonoscopy. Enhanced RADR (OR: 5.36) and PADR (OR: 3.78) were only identified for endocuff. Endocuff comparatively demonstrated the greatest ADR, PDR, and SADR, but this was not significant when compared with the other assist devices. Subgroup analysis of randomized controlled trials identified enhanced PDR and ADR for both cap and endocuff. CONCLUSIONS:Endoscopic assist devices displayed increased ADR and PDR as compared with standard colonoscopy and thus should be widely adopted. A nonsignificant trend was seen toward higher efficacy for the endocuff device.
PMID: 35324485
ISSN: 1539-2031
CID: 5206732
Honoring Asian diversity by collecting Asian subpopulation data in health research [Editorial]
PMID: 35462441
ISSN: 1098-240x
CID: 5205412
Reply to Caldwell et al
PMID: 34864913
ISSN: 1537-6591
CID: 5204022
Gastrointestinal Endoscopy and the Risk of Prosthetic Joint Infection: A Nationwide Database Analysis
BACKGROUND:Current guidelines suggest antibiotics prophylaxis is not necessary for patients with orthopedic prosthetics undergoing gastrointestinal endoscopy. Clinical evidence to support this recommendation is lacking. AIMS/OBJECTIVE:To analyze the association between inpatient gastrointestinal endoscopy and prosthetic joint infection (PJI) in patients with a recent arthroplasty. METHODS:We included patients admitted from July to October of each calendar year (index admissions) who had an arthroplasty in the same calendar year prior to the index admission. We followed the occurrence of PJI for 60 days after the index admission. Only admissions from July to October were chosen as index admissions, and the follow-up period was limited to 60 days because the database structure prohibits the analysis of events in different calendar years. We compared the rate of 60-day PJI between those who had gastrointestinal endoscopy on index admissions to those who had not. We excluded patients aged less than 18 years, who died on index admission, or had any infection in the same calendar year before or during the index admission. RESULTS:Of 1,831,218 patients with arthroplasty, 88,345 met the inclusion criteria, out of which 5,855 had gastrointestinal endoscopy. The rate of 60-day PJI in those who had endoscopy was 0.23%, and in those who had not was 0.52% (P < 0.001). EGD without excision (adjusted odds ratio [95% confidence interval]: 0.20 [0.03-1.42], P = 0.107), EGD with excision (0.58 [0.21-1.60], P = 0.295), colonoscopy without excision (0.43 [0.11-1.72], P = 0.233), colonoscopy with excision (0.31 [0.04-2.21], P = 0.241), and PEG/PEJ (0.38 [0.05-2.71], P = 0.337) were not associated with risk of 60-day PJI. We found no PJI cases in patients underwent esophageal dilation, ERCP, and EUS with FNA. CONCLUSIONS:Gastrointestinal endoscopy in hospitalized patients with a recent previous arthroplasty is not associated with an increased risk of 60-day prosthetic joint infection.
PMID: 35384622
ISSN: 1573-2568
CID: 5201632
A novel opt-in vs opt-out approach to referral-based treatment of tobacco use in Veterans Affairs (VA) primary care clinics: A provider-level randomized controlled trial protocol
To determine whether an opt-out approach is effective for referral to treatment for tobacco use, we designed a clinical reminder for nurses in a primary care setting that provides a referral for patients who smoke cigarettes. We will use a two-arm, cluster-randomized design to assign nurses at the VA New York Harbor Healthcare System to test which mode of referral (opt-in vs opt-out) is more effective. All patients will be referred to evidence-based treatment for tobacco cessation including counseling from the New York State Quitline, and VetsQuit, a text messaging-based system for tobacco cessation counseling. We will measure patient engagement with the referral both in the short and long term to determine if referral modality had an impact on tobacco cessation treatment. We will also measure nurse engagement with the referral before, during, and after the implementation of the reminder to determine whether an opt-out approach is cost effective at the health system level. At the conclusion of this project, we expect to have developed and tested an opt-out system for increasing tobacco cessation treatment for Veterans in VA primary care and to have a thorough understanding of factors associated with implementation. Trial Registration:Clinicaltrials.govIdentifierNCT03477435.
PMID: 35276337
ISSN: 1559-2030
CID: 5200212
