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Toward Implementing Primary Care at Chairside: Developing a Clinical Decision Support System for Dental Hygienists

Russell, Stefanie L; Greenblatt, Ariel Port; Gomes, Danni; Birenz, Shirley; Golembeski, Cynthia A; Shelley, Donna; McGuirk, Matthew; Eisenberg, Elise; Northridge, Mary E
INTRODUCTION: The goal of this project was to use the Consolidated Framework for Implementation Research (CFIR) as the theoretical foundation for developing a web-based clinical decision support system (CDSS) for primary care screening and care coordination by dental hygienists at chairside. METHODS: First, we appraised New York State education and scope of practice requirements for dental hygienists with input from health experts who constituted a Senior Advisory Board for the project, and reviewed current professional guidelines and best practices for tobacco use, hypertension and diabetes screening, and nutrition counseling at chairside. Second, we created algorithms for these four health issues (tobacco, hypertension, diabetes, and nutrition) using evidence-based guidelines endorsed by authoritative professional bodies. Third, an information technology specialist incorporated the algorithms into a tool using an iterative process to refine the CDSS, with input from dental hygienists, dentists, Senior Advisory Board members and research staff. RESULTS: An evidence-based CDSS for use by dental hygienists at chairside for tobacco use, hypertension and diabetes screening, and nutrition counseling was developed with the active participation of the individuals involved in the implementation process. CONCLUSIONS: CDSS technology may potentially be leveraged to enhance primary care screening and coordination by dental hygienists at chairside, leading to improved patient care. Using the CFIR as a pragmatic structure for implementing this intervention across multiple settings, the developed CDSS is available for downloading and adaptation to diverse dental settings and other primary care sensitive conditions.
PMCID:4691286
PMID: 26698000
ISSN: 1532-3390
CID: 1884192

Bicycle helmets are highly protective against traumatic brain injury within a dense urban setting

Sethi, Monica; Heidenberg, Jessica; Wall, Stephen P; Ayoung-Chee, Patricia; Slaughter, Dekeya; Levine, Deborah A; Jacko, Sally; Wilson, Chad; Marshall, Gary; Pachter, H Leon; Frangos, Spiros G
BACKGROUND: New York City (NYC) has made significant roadway infrastructure improvements, initiated a bicycle share program, and enacted Vision Zero, an action plan to reduce traffic deaths and serious injuries. The objective of this study was to examine whether bicycle helmets offer a protective advantage against traumatic brain injury (TBI) within a contemporary dense urban setting with a commitment to road safety. METHODS: A prospective observational study of injured bicyclists presenting to a Level I trauma centre was performed. All bicyclists arriving within 24h of injury were included. Data were collected between February, 2012 and August, 2014 and included demographics, imaging studies (e.g. computed tomography (CT)), injury patterns, and outcomes including Glasgow Coma Scale (GCS) and Injury Severity Score. RESULTS: Of 699 patients, 273 (39.1%) were wearing helmets at the time of injury. Helmeted bicyclists were more likely to have a GCS of 15 (96.3% [95% Confidence Interval (CI), 93.3-98.2] vs. 87.6 [95% CI, 84.1-90.6]) at presentation. Helmeted bicyclists underwent fewer head CTs (40.3% [95% CI, 34.4-46.4] vs. 52.8% [95% CI, 48.0-57.6]) and were less likely to sustain intracranial injury (6.3% [95% CI, 2.6-12.5] vs. 19.7% [14.7-25.6]), including skull fracture (0.9% [95% CI, 0.0-4.9] vs. 15.3% [95% CI, 10.8-20.7]) and subdural hematoma (0.0% [95% CI, 0.0-3.2] vs. 8.1% [95% CI, 4.9-12.5]). Helmeted bicyclists were significantly less likely to sustain significant TBI, i.e. Head AIS >/=3 (2.6% [95% CI: 0.7-4.5] vs.10.6% [7.6-12.5]). Four patients underwent craniotomy while three died; all were un-helmeted. A multivariable logistic regression model showed that helmeted bicyclists were 72% less likely to sustain TBI compared with un-helmeted bicyclists (Adjusted Odds Ratio 0.28, 95% CI 0.12-0.61). CONCLUSIONS: Despite substantial road safety measures in NYC, the protective impact of simple bicycle helmets in the event of a crash remains significant. A re-assessment of helmet laws for urban bicyclists is advisable to most effectively translate Vision Zero from a political action plan to public safety reality.
PMID: 26254573
ISSN: 1879-0267
CID: 1721522

Melamine Nephrotoxicity is Mediated by Hyperuricemia

Zhang, Long; Li, Hong Tian; Wang, Lin Lin; Trachtman, Howard; Trasande, Leonardo; Wang, Pei Xin; Liu, Jian Meng
OBJECTIVE: We tested whether melamine nephrotoxicity was exacerbated by urate (a typical component of renal stones in humans) in rats with hyperuricemiainduced by the uricase inhibitor, potassium oxonate (Oxo). METHODS: Rats were exposed to melamine or Oxo alone or combinations of melamine (200-400 mg/kg) and Oxo (200-600 mg/kg) for 3 consecutive days. Kidney injury was evaluated by renal biochemical functions, histomorphology, and lipid peroxidation. Kidney crystals were analyzed for their composition. RESULTS: Nephrotoxicity was minimal in animals administered melamine or Oxo alone, but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined. All rats in the 400+600 (melamine+Oxo) and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days; no rat died in the 200+400 or 200+200 mg/kg group. Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds. Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys, resembling human stones. CONCLUSION: Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans. Future studies should consider uric acid together with melamine when examining adverse effects in humans.
PMID: 26777910
ISSN: 0895-3988
CID: 1921332

Heart Disease Is Associated With Anthropometric Indices and Change in Body Size Perception Over the Life Course: The Golestan Cohort Study

Garg, Vaani P; Vedanthan, Rajesh; Islami, Farhad; Pourshams, Akram; Poutschi, Hossein; Khademi, Hooman; Naeimi, Mohammad; Malekshah, Akbar Fazel-Tabar; Jafari, Elham; Salahi, Rasool; Kamangar, Farin; Etemadi, Arash; Pharoah, Paul D; Abnet, Christian C; Brennan, Paul; Dawsey, Sanford M; Fuster, Valentin; Boffetta, Paolo; Malekzadeh, Reza
BACKGROUND:Cardiovascular disease and obesity are now becoming leading causes of morbidity and mortality in low- and middle-income countries. OBJECTIVES/OBJECTIVE:We investigated the relationship between prevalent heart disease (HD) and current anthropometric indices and body size perception over time from adolescence to adulthood in Iran. METHODS:We present a cross-sectional analysis of baseline data from a prospective study of adults in Golestan Province, Iran. Demographics, cardiac history, and current anthropometric indices-body mass index, waist circumference, and waist to hip ratio-were recorded. Body size perception for ages 15 years, 30 years, and at the time of interview was assessed via pictograms. Associations of these factors and temporal change in perceived body size with HD were evaluated using multivariable logistic regression models. RESULTS:Complete data were available for 50,044 participants; 6.1% of which reported having HD. Higher body mass index, waist circumference, and waist to hip ratio were associated with HD (p < 0.001). Men had a U-shaped relationship between HD and body size perception at younger ages. For change in body size perception, men and women demonstrated a U-shaped relationship with prevalent HD from adolescence to early adulthood, but a J-shaped pattern from early to late adulthood. CONCLUSIONS:HD was associated with anthropometric indices and change in body size perception over time for men and women in Iran. Due to the increasing prevalence of overweight and obesity in low- and middle-income countries, interventions focused on decreasing the cumulative burden of risk factors throughout the life course may be an important component of cardiovascular risk reduction.
PMCID:4561595
PMID: 26014653
ISSN: 2211-8179
CID: 3239942

Engaging the Entire Care Cascade in Western Kenya: A Model to Achieve the Cardiovascular Disease Secondary Prevention Roadmap Goals

Vedanthan, Rajesh; Kamano, Jemima H; Bloomfield, Gerald S; Manji, Imran; Pastakia, Sonak; Kimaiyo, Sylvester N
Cardiovascular disease (CVD) is the leading cause of death in the world, with a substantial health and economic burden confronted by low- and middle-income countries. In low-income countries such as Kenya, there exists a double burden of communicable and noncommunicable diseases, and the CVD profile includes many nonatherosclerotic entities. Socio-politico-economic realities present challenges to CVD prevention in Kenya, including poverty, low national spending on health, significant out-of-pocket health expenditures, and limited outpatient health insurance. In addition, the health infrastructure is characterized by insufficient human resources for health, medication stock-outs, and lack of facilities and equipment. Within this socio-politico-economic reality, contextually appropriate programs for CVD prevention need to be developed. We describe our experience from western Kenya, where we have engaged the entire care cascade across all levels of the health system, in order to improve access to high-quality, comprehensive, coordinated, and sustainable care for CVD and CVD risk factors. We report on several initiatives: 1) population-wide screening for hypertension and diabetes; 2) engagement of community resources and governance structures; 3) geographic decentralization of care services; 4) task redistribution to more efficiently use of available human resources for health; 5) ensuring a consistent supply of essential medicines; 6) improving physical infrastructure of rural health facilities; 7) developing an integrated health record; and 8) mobile health (mHealth) initiatives to provide clinical decision support and record-keeping functions. Although several challenges remain, there currently exists a critical window of opportunity to establish systems of care and prevention that can alter the trajectory of CVD in low-resource settings.
PMCID:4691279
PMID: 26704963
ISSN: 2211-8179
CID: 3239992

Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial

Ramirez, Claudia E; Nian, Hui; Yu, Chang; Gamboa, Jorge L; Luther, James M; Brown, Nancy J; Shibao, Cyndya A
CONTEXT/BACKGROUND:Sildenafil increases insulin sensitivity in mice. In humans, phosphodiesterase 5 inhibition improves disposition index, but the mechanism of this effect has not been elucidated and may depend on duration. In addition, increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance. OBJECTIVE:The objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with sildenafil improves insulin sensitivity and secretion without diminishing fibrinolytic function. DESIGN/METHODS:This was a randomized, double-blind, placebo-controlled study. SETTING/METHODS:This trial was conducted at Vanderbilt Clinical Research Center. PARTICIPANTS/METHODS:Participants included overweight individuals with prediabetes. INTERVENTIONS/METHODS:Subjects were randomized to treatment with sildenafil 25 mg three times a day or matching placebo for 3 months. Subjects underwent a hyperglycemic clamp prior to and at the end of treatment. MAIN OUTCOME MEASURES/METHODS:The primary outcomes of the study were insulin sensitivity and glucose-stimulated insulin secretion. RESULT/RESULTS:Twenty-one subjects completed each treatment arm. After 3 months, the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group by 1.84 mg/kg/min per μU/mL*100 (95% confidence interval, 0.01 to 3.67 mg/kg/min per μU/mL*100; P = .049), after adjusting for baseline insulin sensitivity index and body mass index. In contrast, there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion (P > .30). Sildenafil decreased plasminogen activator inhibitor-1 (P = .01), without altering tissue-plasminogen activator. In contrast to placebo, sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 ± 14.67 to 6.84 ± 4.86 μg/mg Cr. This effect persisted 3 months after sildenafil discontinuation. CONCLUSIONS:Three-month phosphodiesterase 5 inhibition enhances insulin sensitivity and improves markers of endothelial function.
PMCID:4667163
PMID: 26580240
ISSN: 1945-7197
CID: 5161742

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition

Murray, Christopher J L; Barber, Ryan M; Foreman, Kyle J; Abbasoglu Ozgoren, Ayse; Abd-Allah, Foad; Abera, Semaw F; Aboyans, Victor; Abraham, Jerry P; Abubakar, Ibrahim; Abu-Raddad, Laith J; Abu-Rmeileh, Niveen M; Achoki, Tom; Ackerman, Ilana N; Ademi, Zanfina; Adou, Arsene K; Adsuar, Jose C; Afshin, Ashkan; Agardh, Emilie E; Alam, Sayed Saidul; Alasfoor, Deena; Albittar, Mohammed I; Alegretti, Miguel A; Alemu, Zewdie A; Alfonso-Cristancho, Rafael; Alhabib, Samia; Ali, Raghib; Alla, Francois; Allebeck, Peter; Almazroa, Mohammad A; Alsharif, Ubai; Alvarez, Elena; Alvis-Guzman, Nelson; Amare, Azmeraw T; Ameh, Emmanuel A; Amini, Heresh; Ammar, Walid; Anderson, H Ross; Anderson, Benjamin O; Antonio, Carl Abelardo T; Anwari, Palwasha; Arnlov, Johan; Arsic Arsenijevic, Valentina S; Artaman, Al; Asghar, Rana J; Assadi, Reza; Atkins, Lydia S; Avila, Marco A; Awuah, Baffour; Bachman, Victoria F; Badawi, Alaa; Bahit, Maria C; Balakrishnan, Kalpana; Banerjee, Amitava; Barker-Collo, Suzanne L; Barquera, Simon; Barregard, Lars; Barrero, Lope H; Basu, Arindam; Basu, Sanjay; Basulaiman, Mohammed O; Beardsley, Justin; Bedi, Neeraj; Beghi, Ettore; Bekele, Tolesa; Bell, Michelle L; Benjet, Corina; Bennett, Derrick A; Bensenor, Isabela M; Benzian, Habib; Bernabe, Eduardo; Bertozzi-Villa, Amelia; Beyene, Tariku J; Bhala, Neeraj; Bhalla, Ashish; Bhutta, Zulfiqar A; Bienhoff, Kelly; Bikbov, Boris; Biryukov, Stan; Blore, Jed D; Blosser, Christopher D; Blyth, Fiona M; Bohensky, Megan A; Bolliger, Ian W; Bora Basara, Berrak; Bornstein, Natan M; Bose, Dipan; Boufous, Soufiane; Bourne, Rupert R A; Boyers, Lindsay N; Brainin, Michael; Brayne, Carol E; Brazinova, Alexandra; Breitborde, Nicholas J K; Brenner, Hermann; Briggs, Adam D; Brooks, Peter M; Brown, Jonathan C; Brugha, Traolach S; Buchbinder, Rachelle; Buckle, Geoffrey C; Budke, Christine M; Bulchis, Anne; Bulloch, Andrew G; Campos-Nonato, Ismael R; Carabin, Helene; Carapetis, Jonathan R; Cardenas, Rosario; Carpenter, David O; Caso, Valeria; Castaneda-Orjuela, Carlos A; Castro, Ruben E; Catala-Lopez, Ferran; Cavalleri, Fiorella; Cavlin, Alanur; Chadha, Vineet K; Chang, Jung-Chen; Charlson, Fiona J; Chen, Honglei; Chen, Wanqing; Chiang, Peggy P; Chimed-Ochir, Odgerel; Chowdhury, Rajiv; Christensen, Hanne; Christophi, Costas A; Cirillo, Massimo; Coates, Matthew M; Coffeng, Luc E; Coggeshall, Megan S; Colistro, Valentina; Colquhoun, Samantha M; Cooke, Graham S; Cooper, Cyrus; Cooper, Leslie T; Coppola, Luis M; Cortinovis, Monica; Criqui, Michael H; Crump, John A; Cuevas-Nasu, Lucia; Danawi, Hadi; Dandona, Lalit; Dandona, Rakhi; Dansereau, Emily; Dargan, Paul I; Davey, Gail; Davis, Adrian; Davitoiu, Dragos V; Dayama, Anand; De Leo, Diego; Degenhardt, Louisa; Del Pozo-Cruz, Borja; Dellavalle, Robert P; Deribe, Kebede; Derrett, Sarah; Des Jarlais, Don C; Dessalegn, Muluken; Dharmaratne, Samath D; Dherani, Mukesh K; Diaz-Torne, Cesar; Dicker, Daniel; Ding, Eric L; Dokova, Klara; Dorsey, E Ray; Driscoll, Tim R; Duan, Leilei; Duber, Herbert C; Ebel, Beth E; Edmond, Karen M; Elshrek, Yousef M; Endres, Matthias; Ermakov, Sergey P; Erskine, Holly E; Eshrati, Babak; Esteghamati, Alireza; Estep, Kara; Faraon, Emerito Jose A; Farzadfar, Farshad; Fay, Derek F; Feigin, Valery L; Felson, David T; Fereshtehnejad, Seyed-Mohammad; Fernandes, Jefferson G; Ferrari, Alize J; Fitzmaurice, Christina; Flaxman, Abraham D; Fleming, Thomas D; Foigt, Nataliya; Forouzanfar, Mohammad H; Fowkes, F Gerry R; Paleo, Urbano Fra; Franklin, Richard C; Furst, Thomas; Gabbe, Belinda; Gaffikin, Lynne; Gankpe, Fortune G; Geleijnse, Johanna M; Gessner, Bradford D; Gething, Peter; Gibney, Katherine B; Giroud, Maurice; Giussani, Giorgia; Gomez Dantes, Hector; Gona, Philimon; Gonzalez-Medina, Diego; Gosselin, Richard A; Gotay, Carolyn C; Goto, Atsushi; Gouda, Hebe N; Graetz, Nicholas; Gugnani, Harish C; Gupta, Rahul; Gupta, Rajeev; Gutierrez, Reyna A; Haagsma, Juanita; Hafezi-Nejad, Nima; Hagan, Holly; Halasa, Yara A; Hamadeh, Randah R; Hamavid, Hannah; Hammami, Mouhanad; Hancock, Jamie; Hankey, Graeme J; Hansen, Gillian M; Hao, Yuantao; Harb, Hilda L; Haro, Josep Maria; Havmoeller, Rasmus; Hay, Simon I; Hay, Roderick J; Heredia-Pi, Ileana B; Heuton, Kyle R; Heydarpour, Pouria; Higashi, Hideki; Hijar, Martha; Hoek, Hans W; Hoffman, Howard J; Hosgood, H Dean; Hossain, Mazeda; Hotez, Peter J; Hoy, Damian G; Hsairi, Mohamed; Hu, Guoqing; Huang, Cheng; Huang, John J; Husseini, Abdullatif; Huynh, Chantal; Iannarone, Marissa L; Iburg, Kim M; Innos, Kaire; Inoue, Manami; Islami, Farhad; Jacobsen, Kathryn H; Jarvis, Deborah L; Jassal, Simerjot K; Jee, Sun Ha; Jeemon, Panniyammakal; Jensen, Paul N; Jha, Vivekanand; Jiang, Guohong; Jiang, Ying; Jonas, Jost B; Juel, Knud; Kan, Haidong; Karch, Andre; Karema, Corine K; Karimkhani, Chante; Karthikeyan, Ganesan; Kassebaum, Nicholas J; Kaul, Anil; Kawakami, Norito; Kazanjan, Konstantin; Kemp, Andrew H; Kengne, Andre P; Keren, Andre; Khader, Yousef S; Khalifa, Shams Eldin A; Khan, Ejaz A; Khan, Gulfaraz; Khang, Young-Ho; Kieling, Christian; Kim, Daniel; Kim, Sungroul; Kim, Yunjin; Kinfu, Yohannes; Kinge, Jonas M; Kivipelto, Miia; Knibbs, Luke D; Knudsen, Ann Kristin; Kokubo, Yoshihiro; Kosen, Soewarta; Krishnaswami, Sanjay; Kuate Defo, Barthelemy; Kucuk Bicer, Burcu; Kuipers, Ernst J; Kulkarni, Chanda; Kulkarni, Veena S; Kumar, G Anil; Kyu, Hmwe H; Lai, Taavi; Lalloo, Ratilal; Lallukka, Tea; Lam, Hilton; Lan, Qing; Lansingh, Van C; Larsson, Anders; Lawrynowicz, Alicia E B; Leasher, Janet L; Leigh, James; Leung, Ricky; Levitz, Carly E; Li, Bin; Li, Yichong; Li, Yongmei; Lim, Stephen S; Lind, Maggie; Lipshultz, Steven E; Liu, Shiwei; Liu, Yang; Lloyd, Belinda K; Lofgren, Katherine T; Logroscino, Giancarlo; Looker, Katharine J; Lortet-Tieulent, Joannie; Lotufo, Paulo A; Lozano, Rafael; Lucas, Robyn M; Lunevicius, Raimundas; Lyons, Ronan A; Ma, Stefan; Macintyre, Michael F; Mackay, Mark T; Majdan, Marek; Malekzadeh, Reza; Marcenes, Wagner; Margolis, David J; Margono, Christopher; Marzan, Melvin B; Masci, Joseph R; Mashal, Mohammad T; Matzopoulos, Richard; Mayosi, Bongani M; Mazorodze, Tasara T; Mcgill, Neil W; Mcgrath, John J; Mckee, Martin; Mclain, Abigail; Meaney, Peter A; Medina, Catalina; Mehndiratta, Man Mohan; Mekonnen, Wubegzier; Melaku, Yohannes A; Meltzer, Michele; Memish, Ziad A; Mensah, George A; Meretoja, Atte; Mhimbira, Francis A; Micha, Renata; Miller, Ted R; Mills, Edward J; Mitchell, Philip B; Mock, Charles N; Mohamed Ibrahim, Norlinah; Mohammad, Karzan A; Mokdad, Ali H; Mola, Glen L D; Monasta, Lorenzo; Montanez Hernandez, Julio C; Montico, Marcella; Montine, Thomas J; Mooney, Meghan D; Moore, Ami R; Moradi-Lakeh, Maziar; Moran, Andrew E; Mori, Rintaro; Moschandreas, Joanna; Moturi, Wilkister N; Moyer, Madeline L; Mozaffarian, Dariush; Msemburi, William T; Mueller, Ulrich O; Mukaigawara, Mitsuru; Mullany, Erin C; Murdoch, Michele E; Murray, Joseph; Murthy, Kinnari S; Naghavi, Mohsen; Naheed, Aliya; Naidoo, Kovin S; Naldi, Luigi; Nand, Devina; Nangia, Vinay; Narayan, K M Venkat; Nejjari, Chakib; Neupane, Sudan P; Newton, Charles R; Ng, Marie; Ngalesoni, Frida N; Nguyen, Grant; Nisar, Muhammad I; Nolte, Sandra; Norheim, Ole F; Norman, Rosana E; Norrving, Bo; Nyakarahuka, Luke; Oh, In-Hwan; Ohkubo, Takayoshi; Ohno, Summer L; Olusanya, Bolajoko O; Opio, John Nelson; Ortblad, Katrina; Ortiz, Alberto; Pain, Amanda W; Pandian, Jeyaraj D; Panelo, Carlo Irwin A; Papachristou, Christina; Park, Eun-Kee; Park, Jae-Hyun; Patten, Scott B; Patton, George C; Paul, Vinod K; Pavlin, Boris I; Pearce, Neil; Pereira, David M; Perez-Padilla, Rogelio; Perez-Ruiz, Fernando; Perico, Norberto; Pervaiz, Aslam; Pesudovs, Konrad; Peterson, Carrie B; Petzold, Max; Phillips, Michael R; Phillips, Bryan K; Phillips, David E; Piel, Frederic B; Plass, Dietrich; Poenaru, Dan; Polinder, Suzanne; Pope, Daniel; Popova, Svetlana; Poulton, Richie G; Pourmalek, Farshad; Prabhakaran, Dorairaj; Prasad, Noela M; Pullan, Rachel L; Qato, Dima M; Quistberg, D Alex; Rafay, Anwar; Rahimi, Kazem; Rahman, Sajjad U; Raju, Murugesan; Rana, Saleem M; Razavi, Homie; Reddy, K Srinath; Refaat, Amany; Remuzzi, Giuseppe; Resnikoff, Serge; Ribeiro, Antonio L; Richardson, Lee; Richardus, Jan Hendrik; Roberts, D Allen; Rojas-Rueda, David; Ronfani, Luca; Roth, Gregory A; Rothenbacher, Dietrich; Rothstein, David H; Rowley, Jane T; Roy, Nobhojit; Ruhago, George M; Saeedi, Mohammad Y; Saha, Sukanta; Sahraian, Mohammad Ali; Sampson, Uchechukwu K A; Sanabria, Juan R; Sandar, Logan; Santos, Itamar S; Satpathy, Maheswar; Sawhney, Monika; Scarborough, Peter; Schneider, Ione J; Schottker, Ben; Schumacher, Austin E; Schwebel, David C; Scott, James G; Seedat, Soraya; Sepanlou, Sadaf G; Serina, Peter T; Servan-Mori, Edson E; Shackelford, Katya A; Shaheen, Amira; Shahraz, Saeid; Shamah Levy, Teresa; Shangguan, Siyi; She, Jun; Sheikhbahaei, Sara; Shi, Peilin; Shibuya, Kenji; Shinohara, Yukito; Shiri, Rahman; Shishani, Kawkab; Shiue, Ivy; Shrime, Mark G; Sigfusdottir, Inga D; Silberberg, Donald H; Simard, Edgar P; Sindi, Shireen; Singh, Abhishek; Singh, Jasvinder A; Singh, Lavanya; Skirbekk, Vegard; Slepak, Erica Leigh; Sliwa, Karen; Soneji, Samir; Soreide, Kjetil; Soshnikov, Sergey; Sposato, Luciano A; Sreeramareddy, Chandrashekhar T; Stanaway, Jeffrey D; Stathopoulou, Vasiliki; Stein, Dan J; Stein, Murray B; Steiner, Caitlyn; Steiner, Timothy J; Stevens, Antony; Stewart, Andrea; Stovner, Lars J; Stroumpoulis, Konstantinos; Sunguya, Bruno F; Swaminathan, Soumya; Swaroop, Mamta; Sykes, Bryan L; Tabb, Karen M; Takahashi, Ken; Tandon, Nikhil; Tanne, David; Tanner, Marcel; Tavakkoli, Mohammad; Taylor, Hugh R; Te Ao, Braden J; Tediosi, Fabrizio; Temesgen, Awoke M; Templin, Tara; Ten Have, Margreet; Tenkorang, Eric Y; Terkawi, Abdullah S; Thomson, Blake; Thorne-Lyman, Andrew L; Thrift, Amanda G; Thurston, George D; Tillmann, Taavi; Tonelli, Marcello; Topouzis, Fotis; Toyoshima, Hideaki; Traebert, Jefferson; Tran, Bach X; Trillini, Matias; Truelsen, Thomas; Tsilimbaris, Miltiadis; Tuzcu, Emin M; Uchendu, Uche S; Ukwaja, Kingsley N; Undurraga, Eduardo A; Uzun, Selen B; Van Brakel, Wim H; Van De Vijver, Steven; van Gool, Coen H; Van Os, Jim; Vasankari, Tommi J; Venketasubramanian, N; Violante, Francesco S; Vlassov, Vasiliy V; Vollset, Stein Emil; Wagner, Gregory R; Wagner, Joseph; Waller, Stephen G; Wan, Xia; Wang, Haidong; Wang, Jianli; Wang, Linhong; Warouw, Tati S; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G; Wenzhi, Wang; Werdecker, Andrea; Westerman, Ronny; Whiteford, Harvey A; Wilkinson, James D; Williams, Thomas N; Wolfe, Charles D; Wolock, Timothy M; Woolf, Anthony D; Wulf, Sarah; Wurtz, Brittany; Xu, Gelin; Yan, Lijing L; Yano, Yuichiro; Ye, Pengpeng; Yentur, Gokalp K; Yip, Paul; Yonemoto, Naohiro; Yoon, Seok-Jun; Younis, Mustafa Z; Yu, Chuanhua; Zaki, Maysaa E; Zhao, Yong; Zheng, Yingfeng; Zonies, David; Zou, Xiaonong; Salomon, Joshua A; Lopez, Alan D; Vos, Theo
BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6.2 years (95% UI 5.6-6.6), from 65.3 years (65.0-65.6) in 1990 to 71.5 years (71.0-71.9) in 2013, HALE at birth rose by 5.4 years (4.9-5.8), from 56.9 years (54.5-59.1) to 62.3 years (59.7-64.8), total DALYs fell by 3.6% (0.3-7.4), and age-standardised DALY rates per 100 000 people fell by 26.7% (24.6-29.1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.
PMCID:4673910
PMID: 26321261
ISSN: 1474-547x
CID: 2033262

Somatic and germline analyses of a long term melanoma survivor with a recurrent brain metastasis

Weiss, Sarah; Darvishian, Farbod; Tadepalli, Jyothi; Shapiro, Richard; Golfinos, John; Pavlick, Anna; Polsky, David; Kirchhoff, Tomas; Osman, Iman
BACKGROUND: Median overall survival (OS) of patients with melanoma brain metastases (MBM) is usually 6 months or less. There are rare reports of patients with treated MBM who survived for years. These outlier cases represent valuable opportunities to study the somatic and germline factors that may have influenced patient outcome and led to extended survival. CASE PRESENTATION: Here we report the clinical scenario of a 67 year old man with a recurrent brain metastasis from melanoma who has survived over 12 years post-resection. We review the literature relating to clinical and molecular variables associated with long term survival post-brain metastasis. We present the somatic characteristics of this individual patient's tumor as well as an analysis of inherited genetic variants related to immune function. The patient's resected brain tumor is BRAF V600E mutated, NRAS wild type (WT), and TERT C250T mutated. The patient is a carrier of germline variants in immunomodulatory loci associated with prolonged survival. CONCLUSIONS: Our data suggest that genetic variants in immunomodulatory loci may partially contribute to this patient's unusually favorable outcome and should not be overlooked. With further and future investigation, knowledge of inherited single nucleotide polymorphisms (SNPs) may provide clinicians with more individualized prognostic information for melanoma patients, with potential implications for surveillance strategies and therapeutic interventions.
PMCID:4657192
PMID: 26597176
ISSN: 1471-2407
CID: 1856342

Association between perfluoroalkyl acids and kidney function in a cross-sectional study of adolescents

Kataria, Anglina; Trachtman, Howard; Malaga-Dieguez, Laura; Trasande, Leonardo
BACKGROUND: Perfluoroalkyl acids are synthetic compounds widely used in industrial and commercial applications. Laboratory studies suggest that these persistent and bioaccumulative chemicals produce oxidant stress and damage glomerular endothelial cells, raising concern regarding the impact of these compounds on renal function. METHODS: We performed cross-sectional analyses of data 1960 participants aged 12-19 years of the 2003-2010 National Health and Nutrition Examination Surveys. PFAA exposure was assessed using levels of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid, and perfluorohexane sulfonic acid. Primary study outcomes were estimated glomerular filtration rate (eGFR) and serum uric acid. RESULTS: While adjusting for demographics, cotinine, prehypertension, insulin resistance, body mass index, and hypercholesterolemia, adolescents in the highest PFOA and PFOS quartile had a lower eGFR, 6.84 mL/min/1.73 m2 (95 % CI: 2.19 to 11.48) and 9.69 mL/min/1.73 m2 (95 % CI: -4.59 to 14.78), respectively, compared to the lowest quartile. Highest PFOA and PFOS quartiles were also associated with 0.21 mg/dL (95 % CI: 0.056 to 0.37) and 0.19 mg/dL (95 % CI: 0.032 to 0.34) increases in uric acid, respectively. CONCLUSIONS: PFAAs are associated with a reduction in kidney function and increased uric acid levels in otherwise healthy adolescents. Reverse causation and residual confounding could explain the results. Our study results confirm and amplify previous findings, though longitudinal studies examining prenatal and childhood biomarkers in relationship with robust measures of childhood renal function are needed.
PMCID:4654837
PMID: 26590127
ISSN: 1476-069x
CID: 1848912

RESISTIN DEFICIENCY IN MICE HAS NO EFFECT ON PULMONARY RESPONSES INDUCED BY ACUTE OZONE EXPOSURE

Razvi, Shehla S; Richards, Jeremy B; Malik, Farhan; Cromar, Kevin R; Price, Roger E; Bell, Cynthia S; Weng, Tingting; Atkins, Constance L; Spencer, Chantal Y; Cockerill, Katherine J; Alexander, Amy L; Blackburn, Michael R; Alcorn, Joseph L; Haque, Ikram U; Johnston, Richard A
Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines, including interleukin (IL)-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], tumor necrosis factor (TNF) receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1alpha and IL-1beta), promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1alpha, IL-1beta, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin, yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indices of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1alpha, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient as compared to wild-type mice, no genotype-related differences in the other indices existed following O3 exposure. O3 caused AHR to acetyl-beta-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were non-existent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.
PMCID:4652149
PMID: 26386120
ISSN: 1522-1504
CID: 1779512