Publications by authors named "Lionel Lim"

43 Publications

In high-risk adults aged 50 to 80 y, USPSTF recommends annual lung cancer screening with LDCT (moderate certainty).

Authors:
Lionel S Lim

Ann Intern Med 2021 08 3;174(8):JC86. Epub 2021 Aug 3.

VA Bedford Healthcare System, Bedford, Massachusetts, USA (L.S.L.).

Source Citation: US Preventive Services Task Force; Krist AH, Davidson KW, et al. JAMA. 2021;325:962-70. 33687470.
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http://dx.doi.org/10.7326/ACPJ202108170-086DOI Listing
August 2021

In older adults without CVD, treating 100 persons with statins for 2.5 y prevents 1 MACE.

Authors:
Lionel S Lim

Ann Intern Med 2021 04 6;174(4):JC39. Epub 2021 Apr 6.

VA Bedford Healthcare System, Bedford, Massachusetts, USA (L.S.L.).

Source Citation: Yourman LC, Cenzer IS, Boscardin WJ, et al. JAMA Intern Med. 2021;181:179-85. 33196766.
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http://dx.doi.org/10.7326/ACPJ202104200-039DOI Listing
April 2021

False recognition modality effects in short-term memory: Reversing the auditory advantage.

Cognition 2019 12 25;193:104008. Epub 2019 Jun 25.

Department of Psychology, National University of Singapore, Singapore. Electronic address:

The auditory advantage in short-term false recognition - reduced false memories for auditory compared to visually presented words (Olszewska, Reuter-lorenz, Munier, & Bendler, 2015), has been attributed to greater item distinctiveness in auditory compared to visual memory traces. If so, varying auditory trace distinctiveness should influence false recognition rates. Phonologically and semantically related words were presented visually or aurally. The auditory advantage for semantic lists was replicated but a reversal was observed for phonological lists. Reducing modality-specific acoustic and phonological distinctiveness by increasing phonological similarity led to increased false memory. The findings are consistent with a framework positing the generation of input-dependent memory traces and the role of relative distinctiveness in influencing short-term memory.
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http://dx.doi.org/10.1016/j.cognition.2019.104008DOI Listing
December 2019

Results of a real-world study on vortioxetine in patients with major depressive disorder in South East Asia (REVIDA).

Curr Med Res Opin 2018 11 14;34(11):1975-1984. Epub 2018 Jun 14.

p Lundbeck Singapore Pte Ltd , Singapore.

Objective: The REVIDA study aimed to assess the evolution of major depression symptoms in South East Asian (SEA) patients treated with vortioxetine for major depression in real-world clinical practice.

Methods: This non-interventional study was conducted from August 2016 to April 2017. A total of 138 patients (aged 18-65 years) with an active episode of major depression were recruited from Malaysia, Philippines, Singapore and Thailand. Vortioxetine was initiated on the first visit and patients were followed for 3 months. Depression severity was assessed using the PHQ-9 questionnaire (patient assessed) and CGI-S scale (physician assessed); cognitive function was assessed with the PDQ-D questionnaire; work productivity and activity impairment (WPAI) was assessed with the WPAI questionnaire.

Results: At baseline, 89.9% of patients were moderately to severely depressed (PHQ-9 score ≥10). During the 3 month treatment period, mean ± SD PHQ-9 score decreased from 18.7 ± 5.7 to 5.0 ± 5.3, mean ± SD CGI-S score decreased from 4.4 ± 0.7 to 2.2 ± 1.1 and mean ± SD PDQ-D score decreased from 42.1 ± 18.8 to 13.4 ± 13.0. By Month 3, response and remission rates reached 80.8% and 59.0%, respectively. Work productivity loss decreased from 73.6% to 30.5%, while activity impairment decreased from 71.5% to 24.6%. Positive correlations were observed between PHQ-9, PDQ-D, and WPAI work productivity loss and activity impairment. By Month 3, 82.0% of patients were either not depressed or only mildly depressed (PHQ-9 score ≤9).

Conclusion: In real-world clinical settings, vortioxetine was effective in reducing depression severity and improving cognitive function and work productivity in SEA patients with major depression.
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http://dx.doi.org/10.1080/03007995.2018.1477746DOI Listing
November 2018

MYC-driven inhibition of the glutamate-cysteine ligase promotes glutathione depletion in liver cancer.

EMBO Rep 2017 04 20;18(4):569-585. Epub 2017 Feb 20.

Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA

How MYC reprograms metabolism in primary tumors remains poorly understood. Using integrated gene expression and metabolite profiling, we identify six pathways that are coordinately deregulated in primary MYC-driven liver tumors: glutathione metabolism; glycine, serine, and threonine metabolism; aminoacyl-tRNA biosynthesis; cysteine and methionine metabolism; ABC transporters; and mineral absorption. We then focus our attention on glutathione (GSH) and glutathione disulfide (GSSG), as they are markedly decreased in MYC-driven tumors. We find that fewer glutamine-derived carbons are incorporated into GSH in tumor tissue relative to non-tumor tissue. Expression of GCLC, the rate-limiting enzyme of GSH synthesis, is attenuated by the MYC-induced microRNA miR-18a. Inhibition of miR-18a leads to increased GCLC protein expression and GSH abundance in tumor tissue. Finally, MYC-driven liver tumors exhibit increased sensitivity to acute oxidative stress. In summary, MYC-dependent attenuation of GCLC by miR-18a contributes to GSH depletion , and low GSH corresponds with increased sensitivity to oxidative stress in tumors. Our results identify new metabolic pathways deregulated in primary MYC tumors and implicate a role for MYC in regulating a major antioxidant pathway downstream of glutamine.
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http://dx.doi.org/10.15252/embr.201643068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376764PMC
April 2017

The impact of bevacizumab in metastatic colorectal cancer with an intact primary tumor: Results from a large prospective cohort study.

Asia Pac J Clin Oncol 2017 Aug 25;13(4):314-321. Epub 2016 Nov 25.

Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.

Background: Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood.

Methods: Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT. Progression-free survival (PFS), overall survival (OS) and safety endpoints were analyzed.

Results: Of 1204 mCRC patients, 826 (69%) were eligible for inclusion. Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared with chemotherapy alone, bevacizumab use was associated with significantly longer PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P < 0.001) and OS (IPT: 20 months vs 14.8 months, P = 0.005; RPT: 24.4 months vs 17.3 months, P = 0.004)). Bevacizumab use in an IPT was associated with more GI perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%, P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone. Median survival was equivalent between patients that did or did not experience bevacizumab-related adverse events - 20.0 months versus 19.9 months, hazard ratio = 0.98, P = 0.623. CONCLUSIONS: The addition of bevacizumab significantly improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab-related adverse events did not significantly impact survival outcomes.
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http://dx.doi.org/10.1111/ajco.12639DOI Listing
August 2017

Teaching Pain Management in Interprofessional Medical Education: A Review of Three Portal of Geriatric Online Education Modules.

J Am Geriatr Soc 2016 10 2;64(10):2122-2125. Epub 2016 Sep 2.

Department of Internal Medicine, Griffin Hospital, Derby, Connecticut.

Chronic pain is an international healthcare crisis that affects an estimated 1.5 billion individuals worldwide, but pain management is not emphasized in the medical school curriculum, and thus supplemental education is essential. The Portal of Geriatric Online Education (POGOe) is a free repository of teaching modules for use by geriatric educators and learners. This article highlights three teaching modules available on this site: It's My Old Back Again: An Approach to Diagnosing and Managing Back Pain in the Older Adult (POGOe ID: 21670), Computer Based Learning Workbook, Third Edition module on Pain Management (POGOe ID: 21036), and Aging Q3 Curriculum on Pain Management of Older Adult Patients (POGOe ID: 21187). These modules were chosen based on their ability to address the major topics that the International Association for the Study of Pain proposes should be included in medical school curricula: mulitdimensional nature of pain, pain assessment and measurement, management of pain, and clinical conditions resulting in pain in older adults. They were also selected for their ability to be adapted for interprofessional education and how well they integrate basic science and clinical principles.
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http://dx.doi.org/10.1111/jgs.14309DOI Listing
October 2016

Lifestyle medicine curriculum for a preventive medicine residency program: implementation and outcomes.

Med Educ Online 2016 8;21:29339. Epub 2016 Aug 8.

Institute of Lifestyle Medicine, Physical Medicine & Rehabilitation Service, VA Boston Healthcare System, Brockton, MA, USA.

Background: The vast majority of the healthcare problems burdening our society today are caused by disease-promoting lifestyles (e.g., physical inactivity and unhealthy eating). Physicians report poor training and lack of confidence in counseling patients on lifestyle changes.

Objective: To evaluate a new curriculum and rotation in lifestyle medicine for preventive medicine residents.

Methods: Training included didactics (six sessions/year), distance learning, educational conferences, and newly developed lifestyle medicine rotations at the Institute of Lifestyle Medicine, the Yale-Griffin Prevention Research Center, and the Integrative Medicine Center. We used a number of tools to assess residents' progress including Objective Structured Clinical Examinations (OSCEs), self-assessments, and logs of personal health habits.

Results: A total of 20 residents participated in the lifestyle medicine training between 2010 and 2013. There was a 15% increase in residents' discussions of lifestyle issues with their patients based on their baseline and follow-up surveys. The performance of preventive medicine residents on OSCEs increased each year they were in the program (average OSCE score: PGY1 73%, PGY2 83%, PGY3 87%, and PGY4 91%, p=0.01). Our internal medicine and preliminary residents served as a control, since they did participate in didactics but not in lifestyle medicine rotations. Internal medicine and preliminary residents who completed the same OSCEs had a slightly lower average score (76%) compared with plural for resident, preventive medicine residents (80%). However, this difference did not reach statistical significance (p=0.11).

Conclusion: Incorporating the lifestyle medicine curriculum is feasible for preventive medicine training allowing residents to improve their health behavior change discussions with patients as well as their own personal health habits.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978856PMC
http://dx.doi.org/10.3402/meo.v21.29339DOI Listing
July 2017

Technical Validation of a Next-Generation Sequencing Assay for Detecting Actionable Mutations in Patients with Gastrointestinal Cancer.

J Mol Diagn 2016 05 9;18(3):416-424. Epub 2016 Mar 9.

Genome Institute of Singapore, Singapore; Cancer & Stem Cell Biology Program, Duke-National University of Singapore Graduate Medical School, Singapore; Cancer Science Institute Singapore, National University of Singapore, Singapore; Division of Cellular and Molecular Research, National Cancer Centre Singapore, Singapore. Electronic address:

Targeted next-generation sequencing is becoming increasingly common as a clinical diagnostic and prognostic test for patient- and tumor-specific genetic profiles as well as to optimally select targeted therapies. Here, we describe a custom-developed, next-generation sequencing test for detecting single-nucleotide variants (SNVs) and short insertions and deletions (indels) in 93 genes related to gastrointestinal cancer from routine formalin-fixed, paraffin-embedded clinical specimens. We implemented a validation strategy, based on the College of American Pathologists requirements, using reference DNA mixtures from cell lines with known genetic variants, which model a broad range of allele frequencies. Test sensitivity achieved >99% for both SNVs and indels, with allele frequencies >10%, with high specificity (97.4% for SNVs and 93.6% for indels). We further confirmed test accuracies using primary formalin-fixed, paraffin-embedded colorectal cancer specimens characterized by alternative and conventional clinical diagnostic technologies. Robust performance was observed on the formalin-fixed, paraffin-embedded specimens: sensitivity was 97.2% and specificity was 99.2%. We also observed high intrarun and inter-run reproducibility, as well as a low cross-contamination rate. Overall assessment using cell line samples and formalin-fixed, paraffin-embedded samples showed that our custom next-generation sequencing assay has consistent detection sensitivity down to 10% variant frequency.
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http://dx.doi.org/10.1016/j.jmoldx.2016.01.006DOI Listing
May 2016

Impact of Primary Tumor Site on Bevacizumab Efficacy in Metastatic Colorectal Cancer.

Clin Colorectal Cancer 2016 Jun 13;15(2):e9-e15. Epub 2016 Feb 13.

Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia; Western Health, Department of Medical Oncology, Footscray, Melbourne, Victoria, Australia.

Background: With an ever-increasing focus on personalized medicine, all factors known to affect treatment response need to be considered when defining optimal therapy for individual patients. While the prognostic impact of primary tumor site on colorectal cancer (CRC) outcomes is established, emerging data suggest potential differences in response to biologic therapies. We studied the impact of tumor site on bevacizumab efficacy in patients with metastatic CRC.

Patients And Methods: We analyzed data of patients in an Australian prospective multicenter metastatic CRC (mCRC) registry who received first-line chemotherapy. Tumor site was defined as right colon, cecum to transverse; left colon, splenic flexure to rectosigmoid; and rectum. Kaplan-Meier and Cox models were used for survival analyses.

Results: Of 926 patients, 297 had right colon, 354 left colon, and 275 rectum primary disease. Median age was 68.6, 65.9, and 63.3 years, respectively (P = .001). Right colon disease was significantly associated with intraperitoneal spread (P < .0001), while left colon and rectum disease preferentially metastasized to the liver and lungs, respectively (P < .0001 in both settings). A total of 636 patients (68.7%) received bevacizumab. Progression-free survival was superior for bevacizumab-treated patients in all groups but appeared greatest in right colon disease (hazard ratio, 0.46; 95% confidence interval, 0.36-0.60; P ≤ .001). Overall survival was longest in patients with disease of the rectum, followed by left colon and right colon (median, 26.2, 23.6, and 18.2 months, respectively; P = .0004).

Conclusion: Tumor site appears to be prognostic in mCRC, with rectum and right colon disease associated with the best and worst outcomes, respectively. Patients who received bevacizumab in addition to chemotherapy had superior outcomes, with the effect appearing greatest in patients with right colon disease.
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http://dx.doi.org/10.1016/j.clcc.2016.02.007DOI Listing
June 2016

MicroRNA-494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer.

Hepatology 2014 Jan 22;59(1):202-15. Epub 2013 Nov 22.

Department of Cell & Tissue Biology, University of California San Francisco, San Francisco, CA; Department of Medicine, University of California San Francisco, San Francisco, CA.

Unlabelled: Hepatocellular carcinoma (HCC) is associated with poor survival for patients and few effective treatment options, raising the need for novel therapeutic strategies. MicroRNAs (miRNAs) play important roles in tumor development and show deregulated patterns of expression in HCC. Because of the liver's unique affinity for small nucleic acids, miRNA-based therapy has been proposed in the treatment of liver disease. Thus, there is an urgent need to identify and characterize aberrantly expressed miRNAs in HCC. In our study, we profiled miRNA expression changes in de novo liver tumors driven by MYC and/or RAS, two canonical oncogenes activated in a majority of human HCCs. We identified an up-regulated miRNA megacluster comprised of 53 miRNAs on mouse chromosome 12qF1 (human homolog 14q32). This miRNA megacluster is up-regulated in all three transgenic liver models and in a subset of human HCCs. An unbiased functional analysis of all miRNAs within this cluster was performed. We found that miR-494 is overexpressed in human HCC and aids in transformation by regulating the G1 /S cell cycle transition through targeting of the Mutated in Colorectal Cancer tumor suppressor. miR-494 inhibition in human HCC cell lines decreases cellular transformation, and anti-miR-494 treatment of primary MYC-driven liver tumor formation significantly diminishes tumor size.

Conclusion: Our findings identify a new therapeutic target (miR-494) for the treatment of HCC.
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http://dx.doi.org/10.1002/hep.26662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877416PMC
January 2014

Screening for sudden cardiac death before participation in high school and collegiate sports: American College of Preventive Medicine position statement on preventive practice.

Am J Prev Med 2013 Jul;45(1):130-133

Florida Department of Health in Orange County, CL Brumback Health Center; Department of Family Medicine and Rural Health, Florida State University College of Medicine, Tallahassee; Department of Family Medicine, University of Central Florida College of Medicine, Orlando, Florida.

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http://dx.doi.org/10.1016/j.amepre.2013.04.002DOI Listing
July 2013

Pineapple translation factor SUI1 and ribosomal protein L36 promoters drive constitutive transgene expression patterns in Arabidopsis thaliana.

Plant Mol Biol 2013 Mar 22;81(4-5):327-36. Epub 2012 Dec 22.

University of Queensland, Brisbane, 4072, Australia.

The availability of a variety of promoter sequences is necessary for the genetic engineering of plants, in basic research studies and for the development of transgenic crops. In this study, the promoter and 5' untranslated regions of the evolutionally conserved protein translation factor SUI1 gene and ribosomal protein L36 gene were isolated from pineapple and sequenced. Each promoter was translationally fused to the GUS reporter gene and transformed into the heterologous plant system Arabidopsis thaliana. Both the pineapple SUI1 and L36 promoters drove GUS expression in all tissues of Arabidopsis at levels comparable to the CaMV35S promoter. Transient assays determined that the pineapple SUI1 promoter also drove GUS expression in a variety of climacteric and non-climacteric fruit species. Thus the pineapple SUI1 and L36 promoters demonstrate the potential for using translation factor and ribosomal protein genes as a source of promoter sequences that can drive constitutive transgene expression patterns.
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http://dx.doi.org/10.1007/s11103-012-0002-3DOI Listing
March 2013

IRE1α cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2.

Science 2012 Nov 4;338(6108):818-22. Epub 2012 Oct 4.

Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.

The endoplasmic reticulum (ER) is the primary organelle for folding and maturation of secretory and transmembrane proteins. Inability to meet protein-folding demand leads to "ER stress," and activates IRE1α, an ER transmembrane kinase-endoribonuclease (RNase). IRE1α promotes adaptation through splicing Xbp1 mRNA or apoptosis through incompletely understood mechanisms. Here, we found that sustained IRE1α RNase activation caused rapid decay of select microRNAs (miRs -17, -34a, -96, and -125b) that normally repress translation of Caspase-2 mRNA, and thus sharply elevates protein levels of this initiator protease of the mitochondrial apoptotic pathway. In cell-free systems, recombinant IRE1α endonucleolytically cleaved microRNA precursors at sites distinct from DICER. Thus, IRE1α regulates translation of a proapoptotic protein through terminating microRNA biogenesis, and noncoding RNAs are part of the ER stress response.
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http://dx.doi.org/10.1126/science.1226191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742121PMC
November 2012

HER3 signalling is regulated through a multitude of redundant mechanisms in HER2-driven tumour cells.

Biochem J 2012 Nov;447(3):417-25

Department of Medicine and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA.

HER2 (human epidermal growth factor receptor-2)-amplified tumours are characterized by constitutive signalling via the HER2-HER3 co-receptor complex. Although phosphorylation activity is driven entirely by the HER2 kinase, signal volume generated by the complex is under the control of HER3, and a large capacity to increase its signalling output accounts for the resiliency of the HER2-HER3 tumour driver and accounts for the limited efficacies of anti-cancer drugs designed to target it. In the present paper we describe deeper insights into the dynamic nature of HER3 signalling. Signalling output by HER3 is under several modes of regulation, including transcriptional, post-transcriptional, translational, post-translational and localizational control. These redundant mechanisms can each increase HER3 signalling output and are engaged in various degrees depending on how the HER3/PI3K (phosphoinositide 3-kinase)/Akt/mTOR (mammalian target of rapamycin) signalling network is disturbed. The highly dynamic nature of HER3 expression and signalling, and the plurality of downstream elements and redundant mechanisms that function to ensure HER3 signalling throughput identify HER3 as a major signalling hub in HER2-amplified cancers and a highly resourceful guardian of tumorigenic signalling in these tumours.
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http://dx.doi.org/10.1042/BJ20120724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722874PMC
November 2012

Palliative care teaching in medical residency: a review of two POGO-e teaching products.

J Am Geriatr Soc 2012 Jun 29;60(6):1141-4. Epub 2012 May 29.

Department of Internal Medicine, Griffin Hospital, Derby, Connecticut 06418, USA.

This is a comparison review of GeriaSims and Care of the Aging Medical Patient (CHAMP) modules addressing issues in palliative and hospice medicine found in the Portal of Geriatric Online Education, a free on-line repository of geriatric educational materials for medical educators. GeriaSims is a self-directed teaching module designed to systematically address many of the important questions involved in caring for individuals with chronic progressive and life-limiting illnesses. It is well suited for physicians, particularly medical residents and fellows in-training, who provide care for medically complicated elderly and terminally ill individuals. The CHAMP module is designed to familiarize physician educators with palliative and hospice medicine basics to teach residents and fellows through didactic slides, although it can probably be adapted for use by residents and fellows if audio commentary accompanies the slides. Both modules address practical approaches to addressing palliative care in patients and their families. They are useful teaching tools that address an important learning need and can be readily used to supplement current residency curriculum in hospice and palliative medicine.
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http://dx.doi.org/10.1111/j.1532-5415.2012.03964.xDOI Listing
June 2012

Adding a panel manager to EMR reminders improved some preventive care processes.

Authors:
Lionel S Lim

Ann Intern Med 2012 Jan;156(2):JC1-12

Griffin Hospital, Derby, Connecticut, USA.

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http://dx.doi.org/10.7326/0003-4819-156-2-201201170-02012DOI Listing
January 2012

Atherosclerotic cardiovascular disease screening in adults: American College Of Preventive Medicine position statement on preventive practice.

Am J Prev Med 2011 Mar;40(3):381.e1-10

Departments of Preventive and Internal Medicine, Griffin Hospital, Derby, Connecticut, USA.

Context: Atherosclerotic cardiovascular diseases, including coronary heart disease (CHD), carotid artery stenosis (CAS), peripheral artery disease (PAD), and abdominal aortic aneurysm (AAA), affect millions of U.S. adults and are leading causes of morbidity and mortality. There is some uncertainty regarding the utility of certain screening tests for prevention of cardiovascular morbidity and mortality.

Evidence Acquisition: Current guidelines and studies pertaining to CHD, CAS, PAD, and AAA screening in the adult population were reviewed.

Evidence Synthesis: CHD risk can be estimated by the Framingham Risk Score (FRS), which is valuable in identifying high-risk asymptomatic adults who may benefit from preventive treatments. There is moderate certainty that the benefits of screening do not outweigh the harms for individuals with asymptomatic CAS. The potential harms associated with routine PAD screening in asymptomatic adults are also likely to exceed benefits. Ultrasonography is a safe, noninvasive, and reliable screening test used to identify AAAs for treatment in men aged >65 years who have ever smoked.

Conclusions: American College of Preventive Medicine (ACPM) recommends CHD risk assessment using the FRS to guide risk-based therapy. ACPM does not recommend routine screening of the general adult population using electrocardiogram, exercise-stress testing, computed tomography scanning, ankle-brachial index, carotid intima medial thickness, or emerging risk factors, including high-sensitivity C-reactive protein (hs-CRP). ACPM does not recommend routine screening of the general adult population for CAS or PAD. ACPM recommends one-time AAA screening in men aged 65-75 years who have ever smoked. Routine AAA screening in women is not recommended.
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http://dx.doi.org/10.1016/j.amepre.2010.11.021DOI Listing
March 2011

ACP Journal Club. Use of bisphosphonates was not associated with increased risk for esophageal or gastric cancer.

Authors:
Lionel S Lim

Ann Intern Med 2010 Dec;153(12):JC6-12

Griffin Hospital, Derby, Connecticut, USA.

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http://dx.doi.org/10.7326/0003-4819-153-12-201012210-02012DOI Listing
December 2010

miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma.

Nat Med 2010 Oct 26;16(10):1134-40. Epub 2010 Sep 26.

Cancer Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.

Inactivation of the p53 tumor suppressor pathway allows cell survival in times of stress and occurs in many human cancers; however, normal embryonic stem cells and some cancers such as neuroblastoma maintain wild-type human TP53 and mouse Trp53 (referred to collectively as p53 herein). Here we describe a miRNA, miR-380-5p, that represses p53 expression via a conserved sequence in the p53 3' untranslated region (UTR). miR-380-5p is highly expressed in mouse embryonic stem cells and neuroblastomas, and high expression correlates with poor outcome in neuroblastomas with neuroblastoma derived v-myc myelocytomatosis viral-related oncogene (MYCN) amplification. miR-380 overexpression cooperates with activated HRAS oncoprotein to transform primary cells, block oncogene-induced senescence and form tumors in mice. Conversely, inhibition of endogenous miR-380-5p in embryonic stem or neuroblastoma cells results in induction of p53, and extensive apoptotic cell death. In vivo delivery of a miR-380-5p antagonist decreases tumor size in an orthotopic mouse model of neuroblastoma. We demonstrate a new mechanism of p53 regulation in cancer and stem cells and uncover a potential therapeutic target for neuroblastoma.
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http://dx.doi.org/10.1038/nm.2227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019350PMC
October 2010

Loop diuretic use and rates of hip bone loss and risk of falls and fractures in older women.

J Am Geriatr Soc 2009 May 2;57(5):855-62. Epub 2009 Apr 2.

Departments of Internal Medicine, Griffin Hospital, 130 Division St, Derby, CT 06418, USA.

Objectives: To determine whether loop diuretic use is associated with hip bone loss and greater risk of falls and fractures in older women.

Design: Prospective cohort study from August 1992 to April 2004.

Setting: Four regions in the United States from the Study of Osteoporotic Fractures (SOF).

Participants: Women aged 65 and older (N=8,127) with medication use data who participated in the fourth SOF examination, from which three study cohorts were derived.

Measurements: Bone mineral density (BMD) of the total hip assessed using dual-energy X-ray absorptiometry at the fourth and sixth examinations (n=2,980); recurrent (> or =2) falls in the year after the fourth examination (n=6,244); and incident fracture, including nonspine (n=6,778) and hip fracture (n=7,272).

Results: After multivariable adjustment, loop diuretic users had greater loss of total hip BMD than nonusers (mean annualized % BMD -0.87 vs -0.71, P=.03) after a mean of 4.4+/-0.6 years. The risks of recurrent falls (odds ratio=0.99, 95% confidence interval (CI)=0.71-1.39), nonspine (relative risk (RR)=1.04, 95% CI=0.90-1.21), and hip fracture (RR=1.03, 95% CI=0.81-1.31) were not greater in loop diuretic users than in nonusers.

Conclusion: In this cohort of older women, loop diuretic use was associated with a small but significantly higher rate of hip bone loss than nonuse after a mean duration of 4.4 years, although the risk of falls or fracture did not differ between the two groups.
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http://dx.doi.org/10.1111/j.1532-5415.2009.02195.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721719PMC
May 2009

Screening for osteoporosis in the adult U.S. population: ACPM position statement on preventive practice.

Am J Prev Med 2009 Apr;36(4):366-75

Department of Internal Medicine, Griffin Hospital, Derby, Connecticut, USA.

Context: Osteoporosis is a common and costly disease that is associated with high morbidity and mortality. There is a lack of direct evidence supporting the benefits of bone mineral density (BMD) screening on osteoporosis outcomes. However, there is indirect evidence to support screening for osteoporosis given the availability of medications with good antifracture efficacy. This paper addresses the position of the American College of Preventive Medicine (ACPM) on osteoporosis screening.

Evidence Acquisition: The medical literature was reviewed for studies examining the benefits and harms of osteoporosis screening. An overview is also provided of available modalities for osteoporosis screening, risk-assessment tools, cost effectiveness, benefits and harms of screening, rationale for the study, and recommendations from leading health organizations and ACPM. A review was done of English language articles published prior to September 2008 that were retrieved via search on PubMed, from references from pertinent review or landmark articles, and from websites of leading health organizations.

Evidence Synthesis: There were no randomized controlled trials (RCTs) of osteoporosis screening on fracture outcomes. However, there was one observational study that demonstrated reduced fracture incidence among recipients of BMD testing. Dual energy x-ray absorptiometry is currently one of the most widely accepted and utilized methods for assessing BMD. Other potential tests for detecting osteoporosis include quantitative ultrasound, quantitative computer tomography, and biochemical markers of bone turnover. Testing via BMD is a cost-effective method for detecting osteoporosis in both men and women. Osteoporosis risk-assessment tools such as the WHO fracture-risk algorithm are useful supplements to BMD assessments as they provide estimates of absolute fracture risks. They can also be used with or without BMD testing to assist healthcare providers and patients in making decisions regarding osteoporosis treatments.

Conclusions: All adult patients aged >or=50 years should be evaluated for risk factors for osteoporosis. Screening with BMD testing for osteoporosis is recommended in women aged >or=65 years and in men aged >or=70 years. Younger postmenopausal women and men aged 50-69 years should undergo screening if they have at least one major or two minor risk factors for osteoporosis. It is also recommended that clinicians consider using an osteoporosis risk-assessment tool to evaluate absolute fracture risk to determine appropriate osteoporosis therapies.
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http://dx.doi.org/10.1016/j.amepre.2009.01.013DOI Listing
April 2009

Review of comparative effectiveness of treatments to prevent fractures.

Authors:
Lionel S Lim

Ann Intern Med 2008 Jun;148(11):884-5; author reply 887

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http://dx.doi.org/10.7326/0003-4819-148-11-200806030-00017DOI Listing
June 2008
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