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Gradl G.,RWTH Aachen | Gradl G.,Massachussetts General Hospital | Jupiter J.,Massachussetts General Hospital | Pillukat T.,Rhon Klinikum AG | And 2 more authors.
Archives of Orthopaedic and Trauma Surgery | Year: 2013

Introduction: The purpose of this study was to quantify the clinical and radiographic outcomes after corrective osteotomy for malunions of the distal radius following failed internal fixation. Materials and methods: Results of 18 patients (8 women, 10 men; mean age 41 years) are presented an average of 7 years after osteotomy of a malunited distal radius fracture. We assessed active range of motion, grip strength, radiographic alignment, pain and disability. Subjective and objective data were summarized using the modified Mayo Wrist Score and the point-score system of Fernandez. Results: Wrist motion, pain and deformity improved with the operation in all cases. The modified Mayo Wrist Score averaged 79 points. The scale of Fernandez indicated ten good, two fair and six poor results. Conclusions: The results of this study suggest that the operative correction of a distal radius malunion following an unsuccessful internal fixation can be achieved with outcomes comparable to those reported after initial nonoperative treatment. © 2013 Springer-Verlag Berlin Heidelberg.


Bachireddy C.,Yale University | Soule M.C.,Massachussetts General Hospital | Izenberg J.M.,Yale University | Dvoryak S.,Ukrainian Institute on Public Health Policy | And 2 more authors.
Drug and Alcohol Dependence | Year: 2014

Background: People who inject drugs (PWID) experience poor outcomes and fuel HIV epidemics in middle-income countries in Eastern Europe and Central Asia. We assess integrated/co-located (ICL) healthcare for HIV-infected PWID, which despite international recommendations, is neither widely available nor empirically examined. Methods: A 2010 cross-sectional study randomly sampled 296 HIV-infected opioid-dependent PWID from two representative HIV-endemic regions in Ukraine where ICL, non-co-located (NCL) and harm reduction/outreach (HRO) settings are available. ICL settings provide onsite HIV, addiction, and tuberculosis services, NCLs only treat addiction, and HROs provide counseling, needles/syringes, and referrals, but no opioid substitution therapy (OST). The primary outcome was receipt of quality healthcare, measured using a quality healthcare indicator (QHI) composite score representing percentage of eight guidelines-based recommended indicators met for HIV, addiction and tuberculosis treatment. The secondary outcomes were individual QHIs and health-related quality-of-life (HRQoL). Results: On average, ICL-participants had significantly higher QHI composite scores compared to NCL- and HRO-participants (71.9% versus 54.8% versus 37.0%, p<. 0.001) even after controlling for potential confounders. Compared to NCL-participants, ICL-participants were significantly more likely to receive antiretroviral therapy (49.5% versus 19.2%, p<. 0.001), especially if CD4. ≤. 200 (93.8% versus 62.5% p<. 0.05); guideline-recommended OST dosage (57.3% versus 41.4%, p<. 0.05); and isoniazid preventive therapy (42.3% versus 11.2%, p<. 0.001). Subjects receiving OST had significantly higher HRQoL than those not receiving it (p<. 0.001); however, HRQoL did not differ significantly between ICL- and NCL-participants. Conclusions: These findings suggest that OST alone improves quality-of-life, while receiving care in integrated settings collectively and individually improves healthcare quality indicators for PWID. © 2013 Elsevier Ireland Ltd.


McCluggage W.G.,Royal Group of Hospitals Trust | Hirschowitz L.,Birmingham Womens Hospital | Wilson G.E.,University of Manchester | Oliva E.,Massachussetts General Hospital | And 2 more authors.
American Journal of Surgical Pathology | Year: 2011

The histologic assessment of cervical involvement in endometrial carcinoma may be problematic for a number of reasons, but an accurate evaluation of this is important for correct staging, dictating the need for adjuvant therapy, and prognostication. In this study, we assessed interobserver variation in the evaluation of cervical involvement in hysterectomy specimens of endometrial carcinoma among 6 specialist gynecologic pathologists. Seventy-six cases of endometrial carcinoma enriched for cases exhibiting some perceived issue in the assessment of cervical involvement were used. In all the cases, a single slide of the primary tumor in the uterine corpus and a single slide of the cervix were circulated among the 6 participants who filled in a proforma. On the basis of the responses, the tumors were staged according to the 1988 International Federation of Gynecology and Obstetrics (FIGO) staging system (I, IIA, IIB) and the 2009 FIGO staging system (I, II). Using the 1988 FIGO staging system, the unweighted and weighted κ values between individual observers ranged from 0.3115 to 0.6139 (average 0.4675) and from 0.3492 to 0.6533 (average 0.5065), respectively. The κ values between observers for the 2009 FIGO staging system ranged from 0.3481 to 0.6862 (average 0.4908). Although enriched for problematic cases, our study shows that there is at most a fair-to-good agreement among specialist gynecologic pathologists in the assessment of cervical involvement in endometrial carcinoma. Problematic factors include determination of the junction between the lower uterine segment and upper endocervix, the distinction between "floaters" and true cervical glandular involvement, the distinction between cervical glandular involvement and stromal involvement, and the distinction between cervical glandular involvement and reactive non-neoplastic lesions of the endocervical glands. There is a need for specialist pathology groups dealing with gynecologic cancers to develop and disseminate recommendations regarding the assessment of cervical involvement in endometrial carcinoma. Copyright © 2011 by Lippincott Williams & Wilkins.


Rubin M.F.,Massachussetts General Hospital | Rosas S.E.,Philadelphia Veterans Administration Medical Center | Rosas S.E.,University of Pennsylvania | Chirinos J.A.,Philadelphia Veterans Administration Medical Center | And 2 more authors.
American Journal of Kidney Diseases | Year: 2011

Although clinical cardiovascular outcomes, such as heart attack, stroke, and sudden cardiac death, have a dramatic onset, they result from prolonged exposure to an ever-growing array of risk factors. Several noninvasive procedures are available to assess the cumulative effect of these exposures with the goal of more precisely estimating a person's cardiovascular risk. These include ankle-brachial index, which provides an estimation of obstruction in major-vessel lumen caliber; carotid ultrasound, which evaluates carotid intima-media thickness and plaque, visibly quantifying atherosclerotic burden; aortic pulse wave velocity, which provides a measure of large-artery stiffness; and echocardiography, which measures left ventricular mass, providing a measure of subclinical hypertensive heart disease. In this narrative review, we discuss the role of each of these measures, with a particular emphasis on patients with chronic kidney disease. © 2011 National Kidney Foundation, Inc.


Gradl G.,Massachussetts General Hospital | Gradl G.,University of Rostock | Wendt M.,University of Rostock | Mittlmeier T.,University of Rostock | And 2 more authors.
Archives of Orthopaedic and Trauma Surgery | Year: 2013

Background: The aim of this study was to compare non-bridging external fixation to palmar angular stable plating with respect to radiological outcome, wrist function, and quality of life. Methods: One hundred and two consecutive patients (mean age: 63 years) were enrolled in the study. Fifty-two patients were randomized for plate osteosynthesis (2.4 mm, Synthes), 50 patients received non-bridging external fixation (AO small fixator). Objective (range of motion, grip strength), patient rated outcomes (quality of life, pain), and radiological outcome were assessed 8 weeks, 6 months, and 1 year after surgery. Results: Loss of radial length of more than 3 mm was not detected in any group. Volar tilt was better restored by external fixation (7.2) than by volar plating (0.1). Wrist function was good in both groups. The external fixator was tolerated very well, and the quality of life assessment revealed comparable results in both groups. Osteoporosis was found in 54 % of patients and had no influence on radiological and functional outcome. Conclusion: Non-bridging external fixation employing multiplanar K-wires is a suitable treatment option in intra- and extra-articular fractures of the distal radius even in osteoporotic bone. Level of evidence: Prospective randomized trial, Level I. © 2013 Springer-Verlag Berlin Heidelberg.


Ezell J.,Vanderbilt University | Shui A.,Massachussetts General Hospital | Sanders K.,Vanderbilt University | Veenstra-VanderWeele J.,Columbia University
Pediatrics | Year: 2016

OBJECTIVES: To determine whether adopted children with Autism spectrum disorder (ASD) differ from the general ASD population in terms of diagnosis, internalizing and externalizing behaviors, sleep problems, and medications. METHODS: We studied 163 adoptees in the Autism Speaks Autism Treatment Network (ATN) in comparison with 5624 nonadopted ATN participants (aged 1.5-17.6 years; mean [SD] = 6.2 [3.4] years). Gender, age, race, ethnicity, IQ, and categorical Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, ASD diagnosis were tested for differences by group (adopted versus nonadopted) by using independent-samples t tests for continuous variables and Fisher's exact tests for categorical variables. Logistic or linear regression models were used to examine the association between adoption status and several outcome variables, after controlling for covariates. RESULTS: After controlling for demographics and diagnosis, there were significant differences in group characteristics, including greater propensity for externalizing behavior (P < .001), internalizing behavior (P = .001), and sleep problems (P < .001) in the adopted population. Adoptees were also prescribed psychotropic medications (P < .001) more often than the nonadoptees. Adoptees received a diagnosis of pervasive developmental disorder-not otherwise specified significantly more frequently than controls (odds ratio = 1.8; CI = 1.3- 2.5; P < .001), despite no significant difference in symptoms on standardized measures. CONCLUSIONS: These results suggest that the population of adopted children with ASD differs from the general ASD population both with regard to diagnostic subtype and co-occurring behavioral problems. Future research should evaluate the contributions of specific factors associated with adoption such as biological family history, pregnancy history, early childhood experience, and age at adoption. © 2016 by the American Academy of Pediatrics.


Gradl G.,RWTH Aachen | Gradl G.,Massachussetts General Hospital | Jupiter J.B.,Massachussetts General Hospital
Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca | Year: 2012

Elbow injuries continue to rise with increased athletic activity and life expectancy. Knowledge of anatomy and biomechanics of this sophisticated joint, various injury patterns, and the implication of injury to the static and dynamic stabilizers will result in improvement in specific diagnosis, and therapy. The surgical treatment of trauma to the adult elbow has evolved rapidly in recent years and many useful concepts and techniques have been established. © Česká společnost pro ortopedii a traumatologii 2006.


Palacios N.,Harvard University | Weisskopf M.,Harvard University | Simon K.,Harvard University | Gao X.,Harvard University | And 2 more authors.
Parkinsonism and Related Disorders | Year: 2010

Caffeine intake has been associated with a decreased risk of Parkinson's disease (PD) in men but the effect in women is less clear, and appears to be modified by use of post-menopausal estrogens. In a nested case-control study within the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), we examined associations between single nucleotide polymorphisms (SNPs) of caffeine metabolizing genes (CYP1A2 and NAT2) and estrogen receptors (ESR1 and ESR2), their interaction with caffeine intake and hormone replacement therapy (PMH) use (collected prospectively) and risk of PD. We matched 159 female cases to 724 controls and 139 male cases to 561 controls on birth year, source of DNA (blood or buccal smear), age and sex. The CYP1A2 rs762551 polymorphism (lower enzyme inducibility) was marginally associated with an increased risk of PD (RR, for increasing number of minor alleles = 1.34; 95% CI 1.02, 1.78 in women, but not in men. None of the NAT2 (classified as slow vs. fast acetylator), ESR1 or ESR2 polymorphisms were significantly associated with an altered risk of PD. Marginally significant interactions were observed between caffeine intake and the ESR1 polymorphism rs3798577 (p= 0.07) and ESR2 polymorphism rs1255998 (p= 0.07). The observed increased risk of PD among female but not male carriers of the rs762551 polymorphism of CYP1A2 and the interactions of caffeine with ESR1 rs3798577 and ESR2 rs1255998 may provide clues to explain the relationship between gender, caffeine intake, estrogen status and risk of PD and need to be replicated. © 2010 Elsevier Ltd.


Glajch K.E.,Massachussetts General Hospital | Sadri-Vakili G.,Massachussetts General Hospital
Journal of Huntington's disease | Year: 2015

Transcriptional dysregulation is an early event and may be an important pathological mechanism in Huntington's disease (HD). However, the exact process that leads to alterations in gene expression in HD is not clear. One potential mechanism underlying transcriptional abnormalities in HD may be epigenetic alterations which regulate gene expression without changing the DNA sequence. Previous work has demonstrated that epigenetic marks, such as DNA methylation and post-translational modifications of histone proteins, are significantly altered in HD cellular and animal models as well as HD patients. Furthermore, studies have shown a therapeutic role for histone deacetylase (HDAC) inhibitors in numerous HD …models. Here, we review a range of studies describing epigenetic changes in HD as well as several potential therapeutics that target aberrant epigenetic alterations in HD.


Ausiello D.,Massachussetts General Hospital | Lipnick S.,Massachussetts General Hospital
Big Data | Year: 2015

The next frontier in medicine involves better quantifying human traits, known as "phenotypes." Biological markers have been directly associated with disease risks, but poor measurement of behaviors such as diet and exercise limits our understanding of preventive measures. By joining together an uncommonly wide range of disciplines and expertise, the Kavli HUMAN Project will advance measurement of behavioral phenotypes, as well as environmental factors that impact behavior. By following the same individuals over time, KHP will liberate new understanding of dynamic links between behavioral phenotypes, disease, and the broader environment. As KHP advances understanding of the bio-behavioral complex, it will seed new approaches to the diagnosis, prevention, and treatment of human disease. © Mary Ann Liebert, Inc. 2015.

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