Dartmouth, Lebanon
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Holubar S.D.,One Medical Center Dr | Pendlimari R.,Mayo Medical School | Loftus Jr. E.V.,Mayo Medical School | Larson D.,Mayo Medical School | And 3 more authors.
Diseases of the Colon and Rectum | Year: 2012

BACKGROUND: We previously reported the costs associated with surgery for chronic ulcerative colitis in the Olmsted County population and found that direct medical costs after surgery were significantly reduced compared with before surgery. However, in that study, costs associated with chronic medical therapy for ulcerative colitis were not assessed in nonsurgical patients. OBJECTIVE: To gain insight into the drivers of costs of treatment for chronic ulcerative colitis, we assessed direct costs after surgical and medical therapy in 120 patients in the Rochester Epidemiology Project database. METHODS: A cohort of 60 patients who recovered from surgery for ulcerative colitis from 1988 to 2006 were 1:1 matched by age, sex, and referent year to medically managed patients. Direct health care costs were estimated from an institutional database, and observed cost differences over a 2-year period were calculated. Statistical significance was assessed by paired t tests and bootstrapping; mean costs are adjusted 2009 constant dollars. RESULTS: Two-year direct health care costs in the surgical and medical cohorts were $10,328 vs $6,586 (p = 0.19). In the surgical cohort, Brooke ileostomy patients were observed to have higher costs than patients with ileal pouches (Δ$8187, p = 0.04), and after ileal pouch, pouchitis was associated with increased costs (Δ$12,763, p < 0.01). In the medical cohort, disease extent (Δ$6059, p = 0.04) but not disease severity was associated with increased costs. LIMITATIONS: This study was limited by the relatively small population size and by its performance in a county with a tertiary referral center. CONCLUSIONS: Before the introduction of biologic therapies for ulcerative colitis, patients were observed to have similar health care costs after surgical and medical therapy. In medically treated patients, disease extent was associated with increased costs, whereas in surgically treated patients, permanent ileostomy and pouchitis were observed to be associated with increased costs. © The ASCRS 2012.

Salinas P.D.,One Medical Center Dr | Manning H.L.,One Medical Center Dr
Chest | Year: 2015

A 62-year-old woman presented with a 3-month history of abdominal distension and decreased exercise tolerance. A chest radiograph showed a probable left pleural eff usion ( Fig 1 ). A CT scan of the abdomen revealed a solid ovarian mass with omental caking and a large volume of ascites; there was also confi rmation of a left pleural eff usion. Three days before surgery a CT pulmonary angiogram (CTPA) showed no evidence of pulmonary thromboembolism (PTE). The patient had some improvement in her symptoms after paracentesis and thoracentesis with drainage of 2,000 mL and 250 mL of fl uid, respectively. She underwent total abdominal hysterectomy, bilateral oophorectomy, and partial sigmoid resection with an estimated blood loss of 850 mL. During the operation, she received 5 L of crystalloid and required phenylephrine at 40 to 80 m g/min to maintain a mean arterial pressure . 65 mm Hg. She was extubated after surgery, but immediately after extubation, she became markedly hypotensive and hypoxemic with a BP of 50/20 mm Hg and an oxygen saturation of 70%. An ECG showed T-wave inversions from V1 to V5 and an S1Q3T3 pattern ( Fig 2 ). A bedside echocardiogram showed an enlarged right ventricle (RV), septal dyskinesia, and obliteration of the left ventricle, all consistent with systolic and diastolic RV overload ( Fig 3 ). © 2015 American College Of Chest Physicians.

Karagas M.R.,One Medical Center Dr | Choi A.L.,Harvard University | Oken E.,Harvard University | Horvat M.,Jozef Stefan Institute | And 5 more authors.
Environmental Health Perspectives | Year: 2012

Background: Methylmercury (MeHg) is a known neurotoxicant. Emerging evidence indicates it may have adverse effects on the neurologic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by beneficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited. Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide. Data sources and extraction: We reviewed the published literature for original human epidemiologic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon). ata synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neurologic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardiovascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent. Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and nonlinearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.

Martin B.I.,Dartmouth Hitchcock Medical Center | Deyo R.A.,Oregon Health And Science University | Lurie J.D.,Dartmouth Institute | Carey T.S.,University of North Carolina at Chapel Hill | And 2 more authors.
Spine | Year: 2016

Study Design. An analysis of the State Inpatient Database of North Carolina, 2005 to 2012, and the Nationwide Inpatient Sample, including all inpatient lumbar fusion admissions from nonfederal hospitals. Objective. The aim of the study was to examine the influence of a major commercial policy change that restricted lumbar fusion for certain indications and to forecast the potential impact if the policy were adopted nationally. Summary of Background Data. Few studies have examined the effects of recent changes in commercial coverage policies that restrict the use of lumbar fusion. Methods. We included adults undergoing elective lumbar fusion or re-fusion operations in North Carolina. We aggregated data into a monthly time series to report changes in the rates and volume of lumbar fusion operations for disc herniation or degeneration, spinal stenosis, spondylolisthesis, or revision fusions. Time series regression models were used to test for significant changes in the use of fusion operation following a major commercial coverage policy change initiated on January 1, 2011. Results. There was a substantial decline in the use of lumbar fusion for disc herniation or degeneration following the policy change on January 1, 2011. Overall rates of elective lumbar fusion operations in North Carolina (per 100,000 residents) increased from 103.2 in 2005 to 120.4 in 2009, before declining to 101.9 by 2012. The population rate (per 100,000 residents) of fusion among those under age 65 increased from 89.5 in 2005 to 101.2 in 2009, followed by a sharp decline to 76.8 by 2012. There was no acceleration in the already increasing rate of fusion for spinal stenosis, spondylolisthesis, or revision procedures, but there was a coincident increase in decompression without fusion. Conclusion. This commercial insurance policy change had its intended effect of reducing fusion operations for indications with less evidence of effectiveness without changing rates for other indications or resulting in an overall reduction in spine surgery. Nevertheless, broader adoption of the policy could significantly reduce the national rates of fusion operations and associated costs. © 2016 Wolters Kluwer Health, Inc.

Lahey T.,One Medical Center Dr | Sheth S.,One Medical Center Dr | Matee M.,Muhimbili University of Health and Allied Sciences | Arbeit R.,Tufts University | And 8 more authors.
Journal of Infectious Diseases | Year: 2010

Background. The cellular immune responses that protect against tuberculosis have not been identified. Methods. We assessed baseline interferon γ (IFN-γ) and lymphocyte proliferation assay (LPA) responses to antigen 85 (Ag85), early secretory antigenic target 6 (ESAT-6), and Mycobacterium tuberculosis whole cell lysate (WCL) in human immunodeficiency virus (HIV)-infected and bacille Calmette-Guérin (BCG)-immunized adults with CD4 cell counts of ≥200 cells/μL who received placebo in the DarDar tuberculosis vaccine trial in Tanzania. Subjects were followed prospectively to diagnose definite or probable tuberculosis. Results. Tuberculosis was diagnosed in 92 of 979 subjects during a mean follow-up of 3.2 years. The relative risk of tuberculosis among subjects with positive IFN-γ responses to Ag85 was 0.51 (95% confidence interval [CI], 0.26-0.99; P = .049), to ESAT-6 was 0.44 (95% CI, 0.23-0.85; P = .004), and to WCL was 0.67 (95% CI, 0.49-0.88; P = .002). The relative risk of tuberculosis was not significantly associated with baseline LPA responses. In a multivariate Cox regression model, subjects with IFN-γ responses to ESAT-6 and WCL had a lower hazard of developing tuberculosis, with a hazard ratio for ESAT-6 of 0.35 (95% CI, 0.16-0.77; P = .009) and a hazard ratio for WCL of 0.30 (95% CI, 0.16-0.56; P < .001). Conclusions. Baseline IFN-γ responses to ESAT-6 and WCL were associated with protection from subsequent tuberculosis among HIV-infected subjects with childhood BCG immunization in a region of high tuberculosis prevalence. Trial registration. ClinicalTrials.gov identifier: NCT00052195. © 2010 by the Infectious Diseases Society of America. All rights reserved.

Moore J.H.,One Medical Center Dr | Hill D.P.,One Medical Center Dr
Methods in molecular biology (Clifton, N.J.) | Year: 2015

Here we introduce artificial intelligence (AI) methodology for detecting and characterizing epistasis in genetic association studies. The ultimate goal of our AI strategy is to analyze genome-wide genetics data as a human would using sources of expert knowledge as a guide. The methodology presented here is based on computational evolution, which is a type of genetic programming. The ability to generate interesting solutions while at the same time learning how to solve the problem at hand distinguishes computational evolution from other genetic programming approaches. We provide a general overview of this approach and then present a few examples of its application to real data.

Pearson A.,One Medical Center Dr | Lurie J.,One Medical Center Dr | Tosteson T.,One Medical Center Dr | Zhao W.,One Medical Center Dr | And 3 more authors.
Spine | Year: 2012

STUDY DESIGN.: Combined prospective randomized controlled trial and observational cohort study of intervertebral disc herniation (IDH), an as-treated analysis. OBJECTIVE.: To determine modifiers of the treatment effect (TE) of surgery (the difference between surgical and nonoperative outcomes) for intervertebral disc herniation (IDH) using subgroup analysis. SUMMARY OF BACKGROUND DATA.: The Spine Patient Outcomes Research Trial demonstrated a positive surgical TE for IDH at the group level. However, individual characteristics may affect TE. No prior studies have evaluated TE modifiers in IDH. METHODS.: IDH patients underwent either discectomy (n = 788) or nonoperative care (n = 404) and were analyzed according to treatment received. Thirty-seven baseline variables were used to define subgroups for calculating the time-weighted average TE for the Oswestry Disability Index (ODI) across 4 years (TE = ΔODIsurgery -ΔODInonoperative). Variables with significant subgroup-by-treatment interactions (P < 0.1) were simultaneously entered into a multivariate model to select independent TE predictors. RESULTS.: All analyzed subgroups improved significantly more with surgery than with nonoperative treatment (P < 0.05). In minimally adjusted univariate analyses, being married, absence of joint problems, worsening symptom trend at baseline, high school education or less, older age, no worker's compensation, longer duration of symptoms, and an SF-36 mental component score (MCS) less than 35 were associated with greater TEs. Multivariate analysis demonstrated that being married (TE, -15.8 vs. -7.7 single, P < 0.001), absence of joint problems (TE, -14.6 vs. -10.3 joint problems, P = 0.012), and worsening symptoms (TE, -15.9 vs. -11.8 stable symptoms, P = 0.032) were independent TE modifiers. TEs were greatest in married patients with worsening symptoms (-18.3) vs. single patients with stable symptoms (-7.8). CONCLUSION.: IDH patients who met strict inclusion criteria improved more with surgery than with nonoperative treatment, regardless of specific characteristics. However, being married, without joint problems, and worsening symptom trend at baseline were associated with a greater TE. Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

The recently released third edition of the International Classification of Sleep Disorders (ICSD) is a fully revised version of the American Academy of Sleep Medicine's manual of sleep disorders nosology, published in cooperation with international sleep societies. It is the key reference work for the diagnosis of sleep disorders. The ICSD-3 is built on the same basic outline as the ICSD-2, identifying seven major categories that include insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, and other sleep disorders. Significant modifications have been made to the nosology of insomnia, narcolepsy, and parasomnias. Major features and changes of the manual are reviewed in this article. The rationales for these changes are also discussed. © 2014 American College of Chest Physicians.

PubMed | One Medical Center Dr
Type: Journal Article | Journal: Discovery medicine | Year: 2016

Autoimmune disorders are long-term diseases that adversely affect the quality of life for patients, and they are one of the top ten leading causes of death. While each autoimmune disorder is unique, they all are caused by a breakdown of tolerance against endogenous proteins. This leads to auto-inflammatory events that promote the destruction of organs in a humoral and cellular immune mediated manner. Treatment options for autoimmunity can involve the use of chemical and biologic agents that suppress inflammation. While these treatment options for patients have shown to be beneficial in autoimmunity, they can result in patients being vulnerable to opportunistic infections. Newer therapies aim to identify methods to specifically block auto-inflammatory immune cells while allowing for an intact immune response to other antigens. T regulatory (Treg) cells are a subtype of the adoptive immune cell that is capable of suppressing inflammatory events in an antigen-specific manner, but they are often poorly functioning within autoimmune patients. Treg cells have been well characterized for their immune modulating capabilities and preclinical and early clinical studies support their therapeutic potential for antigen-specific immune suppression. This review will examine the current understanding of Treg cell function and the therapeutic potential of enhancing Treg cells in patients with inflammatory disorders.

Moore J.H.,One Medical Center Dr | Andrews P.C.,One Medical Center Dr
Methods in molecular biology (Clifton, N.J.) | Year: 2015

Here we introduce the multifactor dimensionality reduction (MDR) methodology and software package for detecting and characterizing epistasis in genetic association studies. We provide a general overview of the method and then highlight some of the key functions of the open-source MDR software package that is freely distributed. We end with a few examples of published studies of complex human diseases that have used MDR.

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