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Item Open Access A 15-year consolidated overview of data in over 6000 patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS).(Orphanet journal of rare diseases, 2023-11) Gentile, Luca; Coelho, Teresa; Dispenzieri, Angela; Conceição, Isabel; Waddington-Cruz, Márcia; Kristen, Arnt; Wixner, Jonas; Diemberger, Igor; Gonzalez-Moreno, Juan; Cariou, Eve; Maurer, Mathew S; Planté-Bordeneuve, Violaine; Garcia-Pavia, Pablo; Tournev, Ivailo; Gonzalez-Costello, Jose; Duarte, Alejandra Gonzalez; Grogan, Martha; Mazzeo, Anna; Chapman, Doug; Gupta, Pritam; Glass, Oliver; Amass, Leslie; THAOS investigatorsBackground
Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs.Methods
Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry.Results
This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5).Conclusions
This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis.Trial registration
ClinicalTrials.gov Identifier: NCT00628745.Item Open Access A blood-based biomarker panel to risk-stratify mild traumatic brain injury.(PloS one, 2017-01) Sharma, Richa; Rosenberg, Alexandra; Bennett, Ellen R; Laskowitz, Daniel T; Acheson, Shawn KMild traumatic brain injury (TBI) accounts for the vast majority of the nearly two million brain injuries suffered in the United States each year. Mild TBI is commonly classified as complicated (radiographic evidence of intracranial injury) or uncomplicated (radiographically negative). Such a distinction is important because it helps to determine the need for further neuroimaging, potential admission, or neurosurgical intervention. Unfortunately, imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are costly and not without some risk. The purpose of this study was to screen 87 serum biomarkers to identify a select panel of biomarkers that would predict the presence of intracranial injury as determined by initial brain CT. Serum was collected from 110 patients who sustained a mild TBI within 24 hours of blood draw. Two models were created. In the broad inclusive model, 72kDa type IV collagenase (MMP-2), C-reactive protein (CRP), creatine kinase B type (CKBB), fatty acid binding protein-heart (hFABP), granulocyte-macrophage colony-stimulating factor (GM-CSF) and malondialdehyde modified low density lipoprotein (MDA-LDL) significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.975 and a negative predictive value (NPV) of 98.6. In the parsimonious model, MMP-2, CRP, and CKBB type significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.964 and a negative predictive value (NPV) of 97.2. These results suggest that a serum based biomarker panel can accurately differentiate patients with complicated mild TBI from those with uncomplicated mild TBI. Such a panel could be useful to guide early triage decisions, including the need for further evaluation or admission, especially in those environments in which resources are limited.Item Open Access A case of frontal neuropsychological and neuroimaging signs following multiple primary-blast exposure.(Neurocase, 2012-06) Hayes, Jasmeet Pannu; Morey, Rajendra A; Tupler, Larry ABlast-related traumatic brain injury (TBI) from the Afghanistan and Iraq wars represents a significant medical concern for troops and veterans. To better understand the consequences of primary-blast injury in humans, we present a case of a Marine exposed to multiple primary blasts during his 14-year military career. The neuropsychological profile of this formerly high-functioning veteran suggested primarily executive dysfunction. Diffusion-tensor imaging revealed white-matter pathology in long fiber tracks compared with a composite fractional-anisotropy template derived from a veteran reference control group without TBI. This study supports the existence of primary blast-induced neurotrauma in humans and introduces a neuroimaging technique with potential to discriminate multiple-blast TBI.Item Open Access A case study of inclusion of rural populations in research: Implications for science and health equity.(Clinical and translational science, 2024-08) Noonan, Devon; Lam, Wendy KK; Goodrich, James; Sullivan, Sydney; Bentley-Edwards, Keisha; Koeberl, Dwight; Palipana, Anushka; McClernon, F JosephPrior research highlights that rural populations have been historically underrepresented/excluded from clinical research. The primary objective of this study was to describe the inclusion of rural populations within our research enterprise using Clinical Research Management System demographic information at a large academic medical center in the Southeast. This was a cross-sectional study using participant demographic information for all protocols entered into our Clinical Research Management System between May 2018 and March 2021. Descriptive statistics were used to analyze the representation of rural and non-rural participants and demographic breakdown by age, sex, race, and ethnicity for our entire enterprise and at the state level. We also compared Material Community Deprivation Index levels between urban and rural participants. Results indicated that 19% of the research population was classified as rural and 81% as non-rural for our entire sample, and 17.5% rural and 82.5% urban for our state-level sample. There were significant differences in race, sex, and age between rural and non-rural participants and Material Community Deprivation Indices between rural and non-rural participants. Lessons learned and recommendations for increasing the inclusion of rural populations in research are discussed.Item Open Access A case-control study of airways obstruction among construction workers.(Am J Ind Med, 2015-10) Dement, John; Welch, Laura; Ringen, Knut; Quinn, Patricia; Chen, Anna; Haas, ScottBACKGROUND: While smoking is the major cause of chronic obstructive pulmonary disease (COPD), occupational exposures to vapors, gases, dusts, and fumes (VGDF) increase COPD risk. This case-control study estimated the risk of COPD attributable to occupational exposures among construction workers. METHODS: The study population included 834 cases and 1243 controls participating in a national medical screening program for older construction workers between 1997 and 2013. Qualitative exposure indices were developed based on lifetime work and exposure histories. RESULTS: Approximately 18% (95% CI = 2-24%) of COPD risk can be attributed to construction-related exposures, which are additive to the risk contributed by smoking. A measure of all VGDF exposures combined was a strong predictor of COPD risk. CONCLUSIONS: Construction workers are at increased risk of COPD as a result of broad and complex effects of many exposures acting independently or interactively. Control methods should be implemented to prevent worker exposures, and smoking cessation should be promoted.Item Open Access A clinician's guide to the ABCs of cardiovascular disease prevention: the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and American College of Cardiology Cardiosource Approach to the Million Hearts Initiative.(Clinical cardiology, 2013-07) Hsu, Steven; Ton, Van-Khue; Dominique Ashen, M; Martin, Seth S; Gluckman, Ty J; Kohli, Payal; Sisson, Stephen D; Blumenthal, Roger S; Blaha, Michael JAtherosclerotic cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. Fortunately, it is often preventable with early adoption of lifestyle modification, prevention of risk factor onset, and aggressive treatment of existing risk factors. The Million Hearts Initiative is an effort by the Centers for Disease Control that aims to prevent 1 million myocardial infarctions and strokes over the next 5 years. As part of this initiative, we present a simply organized "ABCDE" approach for guiding a consistent comprehensive approach to managing cardiovascular risk in daily clinical practice. ABCDE stands for assessment of risk, antiplatelet therapy, blood pressure management, cholesterol management, cigarette/tobacco cessation, diet and weight management, diabetes prevention and treatment, and exercise, interventions regularly used to reduce cardiovascular (CV) risk. Throughout this article we summarize recommendations related to each topic and reference landmark trials and data that support our approach. We believe that the ABCDE approach will be the core framework for addressing CV risk in our effort to prevent CVD.Item Open Access A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients.(BMC Musculoskelet Disord, 2015-03-01) Zura, Robert; Mehta, Samir; Rocca, Gregory J Della; Jones, John; Steen, R GrantBACKGROUND: Patient age is one of many potential risk factors for fracture nonunion. Our hypothesis is that older patients (≥ 60) with fracture risk factors treated with low-intensity pulsed ultrasound (LIPUS) have similar heal rate (HR) to the population as a whole. We evaluate the impact of age in conjunction with other risk factors on HR in LIPUS-treated patients with fresh fracture (≤ 90 days old). METHODS: The Exogen Bone Healing System is a LIPUS device approved in 1994 to accelerate healing of fresh fracture. After approval, the FDA required a Post-Market Registry to assess performance. Patient data collected from October 1994 until October 1998 were individually reviewed and validated by a registered nurse. Four distinct data elements were required to report a patient: date fracture occurred; date treatment began; date treatment ended; and a dichotomous outcome of healed v. failed, by clinical and radiological criteria. Data were used to calculate two derived variables; days to treatment (DTT) and days on treatment (DOT). Every validated fresh fracture patient with DTT, DOT, and outcome is reported. RESULTS: The validated registry had 5,765 patients with fresh fracture; 73% (N = 4,190) are reported, while 13% of patients were lost to follow-up, 11% withdrew or were non-compliant, and 3% died or are missing outcome. Among treatment-compliant patients, HR was 96.2%. Logistic estimates of the odds ratio for healing are equivalent for patients age 30 to 79 years and all age cohorts had a HR > 94%. Open fracture, current smoking, diabetes, vascular insufficiency, osteoporosis, cancer, rheumatoid arthritis, and prescription NSAIDs all reduced HR, but older patients (≥ 60) had similar HRs to the population as a whole. DTT was significantly shorter for patients who healed (p < 0.0001). CONCLUSIONS: Comorbid conditions in conjunction with aging can reduce fracture HR. Patients with fracture who used LIPUS had a 96% HR, whereas the expected HR averages 93%. Time to treatment was significantly shorter among patients who healed (p < 0.0001), suggesting that it is beneficial to begin LIPUS treatment early. Older patients (≥ 60) with fracture risk factors treated with LIPUS exhibit similar heal rates to the population as a whole.Item Open Access A comparative analysis of the prevalence and characteristics of cervical malalignment in adults presenting with thoracolumbar spine deformity based on variations in treatment approach over 2 years.(European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2016-08) Jalai, Cyrus M; Passias, Peter G; Lafage, Virginie; Smith, Justin S; Lafage, Renaud; Poorman, Gregory W; Diebo, Bassel; Liabaud, Barthélemy; Neuman, Brian J; Scheer, Justin K; Shaffrey, Christopher I; Bess, Shay; Schwab, Frank; Ames, Christopher P; International Spine Study Group (ISSG)Purpose
Characteristics specific to cervical deformity (CD) concomitant with adult thoracolumbar deformity (TLD) remains uncertain, particularly regarding treatment. This study identifies cervical malalignment prevalence following surgical and conservative TLD treatment through 2 years.Methods
Retrospective analysis of a prospective, multicenter adult spinal deformity (ASD) database. CD was defined in operative and non-operative ASD patients according to the following criteria: T1 Slope minus Cervical Lordosis (T1S-CL) ≥20°, C2-C7 Cervical Sagittal Vertical Axis (cSVA) ≥40 mm, C2-C7 kyphosis >10°. Differences in rates, demographics, health-related quality of life (HRQoL) scores for Oswestry Disability Index (ODI) and Scoliosis Research Society Questionnaire (SRS-22r), and radiographic variables were assessed between treatment groups (Op vs. Non-Op) and follow-up periods (baseline, 1-year, 2-year).Results
Three hundred and nineteen (200 Op, 199 Non-Op) ASD patients were analyzed. Op patients' CD rates at 1 and 2 years were 78.9, and 63.0 %, respectively. Non-Op CD rates were 21.1 and 37.0 % at 1 and 2 years, respectively. T1S-CL mismatch and cSVA malalignment characterized Op CD at 1 and 2 years (p < 0.05). Op and Non-Op CD groups had similar cervical/global alignment at 1 year (p > 0.05 for all), but at 2 years, Op CD patients had worse thoracic kyphosis (TK), T1S-CL, CL, cSVA, C2-T3 SVA, and global SVA compared to Non-Ops (p < 0.05). Op CD patients had worse ODI, and SRS Activity at 1 and 2 years post-operative (p < 0.05), but had greater 2-year SRS Satisfaction scores (p = 0.019).Conclusions
In the first study to compare cervical malalignment at extended follow-up between ASD treatments, CD rates rose overall through 2 years. TLD surgery, resulting in higher CD rates characterized by T1S-CL and cSVA malalignment, produced poorer HRQoL. This information can aid in treatment method decision-making when cervical deformity is present concomitant with TLD.Item Open Access A Comparison of Minimally Invasive and Open Transforaminal Lumbar Interbody Fusion for Grade 1 Degenerative Lumbar Spondylolisthesis: An Analysis of the Prospective Quality Outcomes Database.(Neurosurgery, 2020-09) Chan, Andrew K; Bisson, Erica F; Bydon, Mohamad; Foley, Kevin T; Glassman, Steven D; Shaffrey, Christopher I; Wang, Michael Y; Park, Paul; Potts, Eric A; Shaffrey, Mark E; Coric, Domagoj; Knightly, John J; Fu, Kai-Ming; Slotkin, Jonathan R; Asher, Anthony L; Virk, Michael S; Kerezoudis, Panagiotis; Alvi, Mohammed A; Guan, Jian; Haid, Regis W; Mummaneni, Praveen VBackground
It remains unclear if minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is comparable to traditional, open TLIF because of the limitations of the prior small-sample-size, single-center studies reporting comparative effectiveness.Objective
To compare MI-TLIF to traditional, open TLIF for grade 1 degenerative lumbar spondylolisthesis in the largest study to date by sample size.Methods
We utilized the prospective Quality Outcomes Database registry and queried patients with grade 1 degenerative lumbar spondylolisthesis who underwent single-segment surgery with MI- or open TLIF methods. Outcomes were compared 24 mo postoperatively.Results
A total of 297 patients were included: 72 (24.2%) MI-TLIF and 225 (75.8%) open TLIF. MI-TLIF surgeries had lower mean body mass indexes (29.5 ± 5.1 vs 31.3 ± 7.0, P = .0497) and more worker's compensation cases (11.1% vs 1.3%, P < .001) but were otherwise similar. MI-TLIF had less blood loss (108.8 ± 85.6 vs 299.6 ± 242.2 mL, P < .001), longer operations (228.2 ± 111.5 vs 189.6 ± 66.5 min, P < .001), and a higher return-to-work (RTW) rate (100% vs 80%, P = .02). Both cohorts improved significantly from baseline for 24-mo Oswestry Disability Index (ODI), Numeric Rating Scale back pain (NRS-BP), NRS leg pain (NRS-LP), and Euro-Qol-5 dimension (EQ-5D) (P > .001). In multivariable adjusted analyses, MI-TLIF was associated with lower ODI (β = -4.7; 95% CI = -9.3 to -0.04; P = .048), higher EQ-5D (β = 0.06; 95% CI = 0.01-0.11; P = .02), and higher satisfaction (odds ratio for North American Spine Society [NASS] 1/2 = 3.9; 95% CI = 1.4-14.3; P = .02). Though trends favoring MI-TLIF were evident for NRS-BP (P = .06), NRS-LP (P = .07), and reoperation rate (P = .13), these results did not reach statistical significance.Conclusion
For single-level grade 1 degenerative lumbar spondylolisthesis, MI-TLIF was associated with less disability, higher quality of life, and higher patient satisfaction compared with traditional, open TLIF. MI-TLIF was associated with higher rates of RTW, less blood loss, but longer operative times. Though we utilized multivariable adjusted analyses, these findings may be susceptible to selection bias.Item Open Access A Comparison of Three Different Positioning Techniques on Surgical Corrections and Postoperative Alignment in Cervical Spinal Deformity (CD) Surgery.(Spine, 2021-05) Morse, Kyle W; Lafage, Renaud; Passias, Peter; Ames, Christopher P; Hart, Robert; Shaffrey, Christopher I; Mundis, Gregory; Protopsaltis, Themistocles; Gupta, Munish; Klineberg, Eric; Burton, Doug; Lafage, Virginie; Kim, Han Jo; International Spine Study GroupStudy design
Retrospective review of a prospective multicenter cervical deformity database.Objective
To examine the differences in sagittal alignment correction between three positioning methods in cervical spinal deformity surgery (CD).Summary of background data
Surgical correction for CD is technically demanding and various techniques are utilized to achieve sagittal alignment objectives. The effect of different patient positioning techniques on sagittal alignment correction following CD remains unknown.Methods
Patients with sagittal deformity who underwent a posterior approach (with and without anterior approach) with an upper instrumented vertebra of C6 or above. Patients with Grade 5, 6, or 7 osteotomies were excluded. Positioning groups were Mayfield skull clamp, bivector traction, and halo ring. Preoperative lower surgical sagittal curve (C2-C7), C2-C7 sagittal vertical axis (cSVA), cervical scoliosis, T1 slope minus cervical lordosis (TS-CL), T1 slope (T1S), chin-brow vertebral angle (CBVA), C2-T3 curve, and C2-T3 SVA was assessed and compared with postoperative radiographs. Segmental changes were analyzed using the Fergusson method.Results
Eighty patients (58% female) with a mean age of 60.6 ± 10.5 years (range, 31-83) were included. The mean postoperative C2-C7 lordosis was 7.8° ± 14 and C2-C7 SVA was 34.1 mm ± 15. There were overall significant changes in cervical alignment across the entire cohort, with improvements in T1 slope (P < 0.001), C2-C7 (P < 0.001), TS-CL (P < 0.001), and cSVA (P = 0.006). There were no differences postoperatively of any radiographic parameter between positioning groups (P > 0.05). The majority of segmental lordotic correction was achieved at C4-5-6 (mean 6.9° ± 11). Additionally, patients who had bivector traction applied had had significantly more segmental correction at C7-T1-T2 compared with Mayfield and halo traction (4.2° vs. 0.3° vs. -1.7° respectively, P < 0.027).Conclusion
Postoperative cervical sagittal correction or alignment was not affected by patient position. The majority of segmental correction occurred at C4-5-6 across all positioning methods, while bivector traction had the largest corrective ability at the cervicothoracic junction.Level of Evidence: 4.Item Open Access A conceptual framework for patient-centered fertility treatment.(Reproductive health, 2017-09-07) Duthie, Elizabeth A; Cooper, Alexandra; Davis, Joseph B; Schoyer, Katherine D; Sandlow, Jay; Strawn, Estil Y; Flynn, Kathryn EBACKGROUND:Patient-centered care is a pillar of quality health care and is important to patients experiencing infertility. In this study we used empirical, in-depth data on couples' experiences of infertility treatment decision making to inform and revise a conceptual framework for patient-centered fertility treatment that was developed based on health care professionals' conceptualizations of fertility treatment, covering effectiveness, burden, safety, and costs. METHODS:In this prospective, longitudinal mixed methods study, we collected data from both members (separately) of 37 couples who scheduled an initial consult with a reproductive specialist. Data collection occurred 1 week before the initial consultation, 1 week after the initial consultation, and then roughly 2, 4, 8, and 12 months later. Data collection included semi-structured qualitative interviews, self-reported questionnaires, and medical record review. Interviews were recorded, transcribed, and content analyzed in NVivo. A single coder analyzed all transcripts, with > 25% of transcripts coded by a second coder to ensure quality control and consistency. RESULTS:Content analysis of the interview transcripts revealed 6 treatment dimensions: effectiveness, physical and emotional burden, time, cost, potential risks, and genetic parentage. Thus, the revised framework for patient-centered fertility treatment retains much from the original framework, with modification to one dimension (from safety to potential risks) and the addition of two dimensions (time and genetic parentage). For patients and their partners making fertility treatment decisions, tradeoffs are explicitly considered across dimensions as opposed to each dimension being considered on its own. CONCLUSIONS:Patient-centered fertility treatment should account for the dimensions of treatment that patients and their partners weigh when making decisions about how to add a child to their family. Based on the lived experiences of couples seeking specialist medical care for infertility, this revised conceptual framework can be used to inform patient-centered treatment and research on infertility and to develop decision support tools for patients and providers.Item Open Access A cross-sectional exploratory study of knowledge, attitudes, and practices of emergency health care providers in the assessment of child maltreatment in Maputo, Mozambique.(BMC emergency medicine, 2018-05-09) Pinto, Liliana; Lein, Adriana; Mahoque, Raquel; Wright, David W; Sasser, Scott M; Staton, Catherine ABACKGROUND:In Mozambique, and other low-income countries (LICs), there is little information on the burden of child maltreatment (CM). Emergency care services (ECS) play an important role in recognizing, treating, and intervening in situations of CM. We aim to identify knowledge, attitudes, and practices regarding CM among health care providers in ECS at Mavalane General Hospital in Maputo, Mozambique. METHODS:This exploratory cross-sectional study evaluates the knowledge, attitudes, and practices of health care providers to diagnose and treat cases of CM. A 25 min, pilot-tested verbal interview questionnaire was administered to 49 physicians and nurses working in ECS at Mavalane General Hospital. Interviews were completed between October-November 2010. Data were managed and analyzed in SPSS 14.0 and descriptive statistics were generated. RESULTS:Of 49 health care providers, 83.6% reporting receiving no, or very little CM education or training. Only 61.2% had knowledge of physical abuse as a main form of child maltreatment and 38.8% were able to identify corresponding symptoms of physical abuse. Sexual abuse as a main form of CM was mentioned by 26.5 and 2% cited its symptoms. While 87.7% of health care providers strongly agreed or agreed that they hold an important role in preventing CM, 51.1% also strongly disagreed or disagreed that they feel confident diagnosing and treating CM cases. In regards to follow-up, 14.3% strongly disagreed or disagreed that they know where to refer victims for further follow-up and an additional 14.3% did not know whether they agreed or disagreed. CONCLUSION:This study revealed knowledge gaps in emergency health care provider knowledge of the main forms of CM and their symptoms. The fact that a majority of health care providers in our sample did not receive information specific to CM in their medical education and training could explain this gap, as well as their unawareness of where to refer victims. Given that health care providers believe they play an important role in identifying and treating CM, future research should focus on raising physician awareness of CM and developing education and training materials grounded in cultural contexts to build response capacity in Mozambique and other LICs.Item Open Access A cross-site, comparative effectiveness study of an integrated HIV and substance use treatment program.(AIDS Patient Care STDS, 2010-10) Proeschold-Bell, Rae Jean; Heine, Amy; Pence, Brian Wells; McAdam, Keith; Quinlivan, Evelyn ByrdCo-occurrence of HIV and substance abuse is associated with poor outcomes for HIV-related health and substance use. Integration of substance use and medical care holds promise for HIV patients, yet few integrated treatment models have been reported. Most of the reported models lack data on treatment outcomes in diverse settings. This study examined the substance use outcomes of an integrated treatment model for patients with both HIV and substance use at three different clinics. Sites differed by type and degree of integration, with one integrated academic medical center, one co-located academic medical center, and one co-located community health center. Participants (n=286) received integrated substance use and HIV treatment for 12 months and were interviewed at 6-month intervals. We used linear generalized estimating equation regression analysis to examine changes in Addiction Severity Index (ASI) alcohol and drug severity scores. To test whether our treatment was differentially effective across sites, we compared a full model including site by time point interaction terms to a reduced model including only site fixed effects. Alcohol severity scores decreased significantly at 6 and 12 months. Drug severity scores decreased significantly at 12 months. Once baseline severity variation was incorporated into the model, there was no evidence of variation in alcohol or drug score changes by site. Substance use outcomes did not differ by age, gender, income, or race. This integrated treatment model offers an option for treating diverse patients with HIV and substance use in a variety of clinic settings. Studies with control groups are needed to confirm these findings.Item Open Access A defensive mindset: A pattern of social information processing that develops early and predicts life course outcomes.(Child development, 2022-07) Dodge, Kenneth A; Bai, Yu; Godwin, Jennifer; Lansford, Jennifer E; Bates, John E; Pettit, Gregory S; Jones, DamonThe hypothesis was tested that some children develop a defensive mindset that subsumes individual social information processing (SIP) steps, grows from early experiences, and guides long-term outcomes. In Study 1 (Fast Track [FT]), 463 age-5 children (45% girls; 43% Black) were first assessed in 1991 and followed through age 32 (83% retention). In Study 2 (Child Development Project [CDP]), 585 age-5 children (48% girls, 17% Black) were first assessed in 1987 and followed through age 34 (78% retention). In both studies, measures were collected of early adverse experiences, defensive mindset and SIP, and adult outcomes. Across both studies, a robust latent construct of school-age defensive mindset was validated empirically (comparative fit index = .99 in each study) and found to mediate the impact of early child abuse (38% in FT and 29% in CDP of total effect) and peer social rejection (14% in FT and 7% in CDP of total effect) on adult incarceration.Item Open Access A depth aftereffect caused by viewing a rotating Ames window.(Perception, 1982-01) Rubin, DCAfter a rotating Ames window has been viewed, a normal test window held diagonal to the subject's line of sight appears to be distorted, having a larger back than front. The effect does not occur if a normal window is rotated or if the test window is held perpendicular to the subject's line of sight.Item Open Access A dimensional approach to understanding severity estimates and risk correlates of marijuana abuse and dependence in adults.(International journal of methods in psychiatric research, 2012-06) Wu, Li-Tzy; Woody, George E; Yang, Chongming; Pan, Jeng-Jong; Reeve, Bryce B; Blazer, Dan GWhile item response theory (IRT) research shows a latent severity trait underlying response patterns of substance abuse and dependence symptoms, little is known about IRT-based severity estimates in relation to clinically relevant measures. In response to increased prevalences of marijuana-related treatment admissions, an elevated level of marijuana potency, and the debate on medical marijuana use, we applied dimensional approaches to understand IRT-based severity estimates for marijuana use disorders (MUDs) and their correlates while simultaneously considering gender- and race/ethnicity-related differential item functioning (DIF). Using adult data from the 2008 National Survey on Drug Use and Health (N = 37,897), Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for MUDs among past-year marijuana users were examined by IRT, logistic regression, and multiple indicators-multiple causes (MIMIC) approaches. Among 6917 marijuana users, 15% met criteria for a MUD; another 24% exhibited subthreshold dependence. Abuse criteria were highly correlated with dependence criteria (correlation = 0.90), indicating unidimensionality; item information curves revealed redundancy in multiple criteria. MIMIC analyses showed that MUD criteria were positively associated with weekly marijuana use, early marijuana use, other substance use disorders, substance abuse treatment, and serious psychological distress. African Americans and Hispanics showed higher levels of MUDs than Whites, even after adjusting for race/ethnicity-related DIF. The redundancy in multiple criteria suggests an opportunity to improve efficiency in measuring symptom-level manifestations by removing low-informative criteria. Elevated rates of MUDs among African Americans and Hispanics require research to elucidate risk factors and improve assessments of MUDs for different racial/ethnic groups.Item Open Access A Functional Polymorphism (rs2494752) in the AKT1 Promoter Region and Gastric Adenocarcinoma Risk in an Eastern Chinese Population.(Scientific reports, 2016-01-28) Wang, Meng-Yun; He, Jing; Zhu, Mei-Ling; Teng, Xiao-Yan; Li, Qiao-Xin; Sun, Meng-Hong; Wang, Xiao-Feng; Yang, Ya-Jun; Wang, Jiu-Cun; Jin, Li; Wang, Ya-Nong; Wei, Qing-YiAKT is an important signal transduction protein that plays a crucial role in cancer development. Therefore, we evaluated associations between single nucleotide polymorphisms (SNPs) in the AKT promoter region and gastric cancer (GCa) risk in a case-control study of 1,110 GCa patients and 1,114 matched cancer-free controls. We genotyped five SNPs (AKT1 rs2494750G >C, AKT1 rs2494752A >G, AKT1 rs10138227C >T, AKT2 rs7254617G>A and AKT2 rs2304186G >T) located in the 5' upstream regulatory, first intron or promoter regions. In the logistic regression analysis, a significantly elevated GCa risk was associated with the rs2494752 AG/GG variant genotypes (adjusted odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.02-1.42) under a dominant genetic model, and this risk was more evident in subgroups of ever drinkers. The luciferase reporter assay showed that the rs2494752 G allele significantly increased luciferase activity. Our results suggest that the potentially functional AKT1 rs2494752 SNP may affect GCa susceptibility, likely by modulating the AKT1 promoter transcriptional activity. Larger, independent studies are warranted to validate our findings.Item Open Access A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population.(BMC cancer, 2011-01) Zhou, Keke; Hu, Dezhi; Lu, Juan; Fan, Weiwei; Liu, Hongliang; Chen, Hongyan; Chen, Gong; Wei, Qingyi; Du, Guhong; Mao, Ying; Lu, Daru; Zhou, LiangfuBACKGROUND: The human apurinic/apyrimidinic endonuclease 1/Redox effector factor-1 (APE1/Ref-1) is implicated in tumor development and progression. Recently, the APE1/Ref-1 promoter -141T/G variant (rs1760944) has been reported to be associated with lung cancer risk. Given the importance of APE1/Ref-1 in both DNA repair and redox activity, we speculate that the -141T/G polymorphism may confer individual susceptibility to gliomas or its subtypes. METHODS: The APE1/Ref-1 -141T/G polymorphism was analyzed in a case-control study including 766 glioma patients (among them 241 glioblastoma, 284 astrocytomas except for glioblastoma and 241 other gliomas) and 824 cancer-free controls from eastern China. Genotyping was performed with Sequenom MassARRAY iPLEX platform by use of allele-specific MALDI-TOF mass spectrometry assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression. A test of trend was calculated using the genotype as an ordinal variable in the regression model. For each statistically significant association identified, we estimated the false positive reporting probability (FPRP). FPRP values less than 0.2 were consider to indicate robust associations. RESULTS: The significant association between the APE1/Ref-1 promoter -141T/G polymorphism and glioma risk was not observed. However, the stratified analysis by histology revealed the variant allele G significantly decreased glioblastoma risk (OR = 0.80, 95% CI = 0.65-0.98, P = 0.032). Individuals with the homozygous -141GG genotype exhibited 46% reduced risk of glioblastoma (adjusted OR = 0.54, 95% CI 0.34-0.87, P = 0.012), compared with the TT homozygote. This result remained robust given the prior probabilities of 25% (FPRP = 0.052) and 10% (FPRP = 0.140), but not with a prior probability of 1% (FPRP = 0.643). The P-associated with the trend test was 0.014. CONCLUSIONS: Our results suggest that a specific genetic variant located in the APE1/Ref-1 promoter may modulate risk of glioblastoma, but not for other histological gliomas. Larger studies with more APE1 polymorphisms are required to validate these preliminary findings.Item Open Access A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.(PLoS Genet, 2010-02-19) Tsai, Fuu-Jen; Yang, Chi-Fan; Chen, Ching-Chu; Chuang, Lee-Ming; Lu, Chieh-Hsiang; Chang, Chwen-Tzuei; Wang, Tzu-Yuan; Chen, Rong-Hsing; Shiu, Chiung-Fang; Liu, Yi-Min; Chang, Chih-Chun; Chen, Pei; Chen, Chien-Hsiun; Fann, Cathy SJ; Chen, Yuan-Tsong; Wu, Jer-YuarnTo investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.Item Open Access A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.(PLoS genetics, 2011-03-17) McKay, James D; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun; Byrnes, Graham; Zaridze, David; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Holcatova, Ivana; Janout, Vladimir; Foretova, Lenka; Lagiou, Pagona; Trichopoulos, Dimitrios; Benhamou, Simone; Bouchardy, Christine; Ahrens, Wolfgang; Merletti, Franco; Richiardi, Lorenzo; Talamini, Renato; Barzan, Luigi; Kjaerheim, Kristina; Macfarlane, Gary J; Macfarlane, Tatiana V; Simonato, Lorenzo; Canova, Cristina; Agudo, Antonio; Castellsagué, Xavier; Lowry, Ray; Conway, David I; McKinney, Patricia A; Healy, Claire M; Toner, Mary E; Znaor, Ariana; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wünsch-Filho, Victor; Neto, José Eluf; Garrote, Leticia Fernández; Boccia, Stefania; Cadoni, Gabriella; Arzani, Dario; Olshan, Andrew F; Weissler, Mark C; Funkhouser, William K; Luo, Jingchun; Lubiński, Jan; Trubicka, Joanna; Lener, Marcin; Oszutowska, Dorota; Schwartz, Stephen M; Chen, Chu; Fish, Sherianne; Doody, David R; Muscat, Joshua E; Lazarus, Philip; Gallagher, Carla J; Chang, Shen-Chih; Zhang, Zuo-Feng; Wei, Qingyi; Sturgis, Erich M; Wang, Li-E; Franceschi, Silvia; Herrero, Rolando; Kelsey, Karl T; McClean, Michael D; Marsit, Carmen J; Nelson, Heather H; Romkes, Marjorie; Buch, Shama; Nukui, Tomoko; Zhong, Shilong; Lacko, Martin; Manni, Johannes J; Peters, Wilbert HM; Hung, Rayjean J; McLaughlin, John; Vatten, Lars; Njølstad, Inger; Goodman, Gary E; Field, John K; Liloglou, Triantafillos; Vineis, Paolo; Clavel-Chapelon, Francoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; González, Carlos A; Quirós, J Ramón; Martínez, Carmen; Navarro, Carmen; Ardanaz, Eva; Larrañaga, Nerea; Khaw, Kay-Tee; Key, Timothy; Bueno-de-Mesquita, H Bas; Peeters, Petra HM; Trichopoulou, Antonia; Linseisen, Jakob; Boeing, Heiner; Hallmans, Göran; Overvad, Kim; Tjønneland, Anne; Kumle, Merethe; Riboli, Elio; Välk, Kristjan; Vooder, Tõnu; Metspalu, Andres; Zelenika, Diana; Boland, Anne; Delepine, Marc; Foglio, Mario; Lechner, Doris; Blanché, Hélène; Gut, Ivo G; Galan, Pilar; Heath, Simon; Hashibe, Mia; Hayes, Richard B; Boffetta, Paolo; Lathrop, Mark; Brennan, PaulGenome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.