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  • Cervical screening with primary HPV testing or cytology in a population of women in which those aged 33 years or younger had previously been offered HPV vaccination: Results of the Compass pilot randomised trial
    PLOS Med. (IF 11.862) Pub Date : 2017-09-19
    Karen Canfell, Michael Caruana, Val Gebski, Jessica Darlington-Brown, Stella Heley, Julia Brotherton, Dorota Gertig, Chloe J. Jennett, Annabelle Farnsworth, Jeffrey Tan, C. David Wrede, Philip E. Castle, Marion Saville
    更新日期:2017-09-20
  • Self-monitoring of blood pressure in hypertension: A systematic review and individual patient data meta-analysis
    PLOS Med. (IF 11.862) Pub Date : 2017-09-19
    Katherine L. Tucker, James P. Sheppard, Richard Stevens, Hayden B. Bosworth, Alfred Bove, Emma P. Bray, Kenneth Earle, Johnson George, Marshall Godwin, Beverly B. Green, Paul Hebert, F. D. Richard Hobbs, Ilkka Kantola, Sally M. Kerry, Alfonso Leiva, David J. Magid, Jonathan Mant, Karen L. Margolis, Brian McKinstry, Mary Ann McLaughlin, Stefano Omboni, Olugbenga Ogedegbe, Gianfranco Parati, Nashat Qamar, Bahman P. Tabaei, Juha Varis, Willem J. Verberk, Bonnie J. Wakefield, Richard J. McManus
    更新日期:2017-09-20
  • Global services and support for children with developmental delays and disabilities: Bridging research and policy gaps
    PLOS Med. (IF 11.862) Pub Date : 2017-09-18
    Pamela Y. Collins, Beverly Pringle, Charlee Alexander, Gary L. Darmstadt, Jody Heymann, Gillian Huebner, Vesna Kutlesic, Cheryl Polk, Lorraine Sherr, Andy Shih, Dragana Sretenov, Mariana Zindel
    更新日期:2017-09-19
  • Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis
    PLOS Med. (IF 11.862) Pub Date : 2017-09-12
    Eleanor Wheeler, Aaron Leong, Ching-Ti Liu, Marie-France Hivert, Rona J. Strawbridge, Clara Podmore, Man Li, Jie Yao, Xueling Sim, Jaeyoung Hong, Audrey Y. Chu, Weihua Zhang, Xu Wang, Peng Chen, Nisa M. Maruthur, Bianca C. Porneala, Stephen J. Sharp, Yucheng Jia, Edmond K. Kabagambe, Li-Ching Chang, Wei-Min Chen, Cathy E. Elks, Daniel S. Evans, Qiao Fan, Franco Giulianini, Min Jin Go, Jouke-Jan Hottenga, Yao Hu, Anne U. Jackson, Stavroula Kanoni, Young Jin Kim, Marcus E. Kleber, Claes Ladenvall, Cecile Lecoeur, Sing-Hui Lim, Yingchang Lu, Anubha Mahajan, Carola Marzi, Mike A. Nalls, Pau Navarro, Ilja M. Nolte, Lynda M. Rose, Denis V. Rybin, Serena Sanna, Yuan Shi, Daniel O. Stram, Fumihiko Takeuchi, Shu Pei Tan, Peter J. van der Most, Jana V. Van Vliet-Ostaptchouk, Andrew Wong, Loic Yengo, Wanting Zhao, Anuj Goel, Maria Teresa Martinez Larrad, Dörte Radke, Perttu Salo, Toshiko Tanaka, Erik P. A. van Iperen, Goncalo Abecasis, Saima Afaq, Behrooz Z. Alizadeh, Alain G. Bertoni, Amelie Bonnefond, Yvonne Böttcher, Erwin P. Bottinger, Harry Campbell, Olga D. Carlson, Chien-Hsiun Chen, Yoon Shin Cho, W. Timothy Garvey, Christian Gieger, Mark O. Goodarzi, Harald Grallert, Anders Hamsten, Catharina A. Hartman, Christian Herder, Chao Agnes Hsiung, Jie Huang, Michiya Igase, Masato Isono, Tomohiro Katsuya, Chiea-Chuen Khor, Wieland Kiess, Katsuhiko Kohara, Peter Kovacs, Juyoung Lee, Wen-Jane Lee, Benjamin Lehne, Huaixing Li, Jianjun Liu, Stephane Lobbens, Jian'an Luan, Valeriya Lyssenko, Thomas Meitinger, Tetsuro Miki, Iva Miljkovic, Sanghoon Moon, Antonella Mulas, Gabriele Müller, Martina Müller-Nurasyid, Ramaiah Nagaraja, Matthias Nauck, James S. Pankow, Ozren Polasek, Inga Prokopenko, Paula S. Ramos, Laura Rasmussen-Torvik, Wolfgang Rathmann, Stephen S. Rich, Neil R. Robertson, Michael Roden, Ronan Roussel, Igor Rudan, Robert A. Scott, William R. Scott, Bengt Sennblad, David S. Siscovick, Konstantin Strauch, Liang Sun, Morris Swertz, Salman M. Tajuddin, Kent D. Taylor, Yik-Ying Teo, Yih Chung Tham, Anke Tönjes, Nicholas J. Wareham, Gonneke Willemsen, Tom Wilsgaard, Aroon D. Hingorani, EPIC-CVD Consortium, EPIC-InterAct Consortium, Lifelines Cohort Study, Josephine Egan, Luigi Ferrucci, G. Kees Hovingh, Antti Jula, Mika Kivimaki, Meena Kumari, Inger Njølstad, Colin N. A. Palmer, Manuel Serrano Ríos, Michael Stumvoll, Hugh Watkins, Tin Aung, Matthias Blüher, Michael Boehnke, Dorret I. Boomsma, Stefan R. Bornstein, John C. Chambers, Daniel I. Chasman, Yii-Der Ida Chen, Yduan-Tsong Chen, Ching-Yu Cheng, Francesco Cucca, Eco J. C. de Geus, Panos Deloukas, Michele K. Evans, Myriam Fornage, Yechiel Friedlander, Philippe Froguel, Leif Groop, Myron D. Gross, Tamara B. Harris, Caroline Hayward, Chew-Kiat Heng, Erik Ingelsson, Norihiro Kato, Bong-Jo Kim, Woon-Puay Koh, Jaspal S. Kooner, Antje Körner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Xu Lin, Yongmei Liu, Ruth J. F. Loos, Patrik K. E. Magnusson, Winfried März, Mark I. McCarthy, Albertine J. Oldehinkel, Ken K. Ong, Nancy L. Pedersen, Mark A. Pereira, Annette Peters, Paul M. Ridker, Charumathi Sabanayagam, Michele Sale, Danish Saleheen, Juha Saltevo, Peter EH. Schwarz, Wayne H. H. Sheu, Harold Snieder, Timothy D. Spector, Yasuharu Tabara, Jaakko Tuomilehto, Rob M. van Dam, James G. Wilson, James F. Wilson, Bruce H. R. Wolffenbuttel, Tien Yin Wong, Jer-Yuarn Wu, Jian-Min Yuan, Alan B. Zonderman, Nicole Soranzo, Xiuqing Guo, David J. Roberts, Jose C. Florez, Robert Sladek, Josée Dupuis, Andrew P. Morris, E-Shyong Tai, Elizabeth Selvin, Jerome I. Rotter, Claudia Langenberg, Inês Barroso, James B. Meigs
    更新日期:2017-09-12
  • Sustained effectiveness and cost-effectiveness of the Healthy Activity Programme, a brief psychological treatment for depression delivered by lay counsellors in primary care: 12-month follow-up of a randomised controlled trial
    PLOS Med. (IF 11.862) Pub Date : 2017-09-12
    Benedict Weobong, Helen A. Weiss, David McDaid, Daisy R. Singla, Steven D. Hollon, Abhijit Nadkarni, A-La Park, Bhargav Bhat, Basavraj Katti, Arpita Anand, Sona Dimidjian, Ricardo Araya, Michael King, Lakshmi Vijayakumar, G. Terence Wilson, Richard Velleman, Betty R. Kirkwood, Christopher G. Fairburn, Vikram Patel
    更新日期:2017-09-12
  • Sustained effectiveness and cost-effectiveness of Counselling for Alcohol Problems, a brief psychological treatment for harmful drinking in men, delivered by lay counsellors in primary care: 12-month follow-up of a randomised controlled trial
    PLOS Med. (IF 11.862) Pub Date : 2017-09-12
    Abhijit Nadkarni, Helen A. Weiss, Benedict Weobong, David McDaid, Daisy R. Singla, A-La Park, Bhargav Bhat, Basavaraj Katti, Jim McCambridge, Pratima Murthy, Michael King, G. Terence Wilson, Betty Kirkwood, Christopher G. Fairburn, Richard Velleman, Vikram Patel
    更新日期:2017-09-12
  • Effectiveness of food supplements in increasing fat-free tissue accretion in children with moderate acute malnutrition: A randomised 2 × 2 × 3 factorial trial in Burkina Faso
    PLOS Med. (IF 11.862) Pub Date : 2017-09-11
    Christian Fabiansen, Charles W. Yaméogo, Ann-Sophie Iuel-Brockdorf, Bernardette Cichon, Maren J. H. Rytter, Anura Kurpad, Jonathan C. Wells, Christian Ritz, Per Ashorn, Suzanne Filteau, André Briend, Susan Shepherd, Vibeke B. Christensen, Kim F. Michaelsen, Henrik Friis
    更新日期:2017-09-11
  • Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study
    PLOS Med. (IF 11.862) Pub Date : 2017-09-07
    Robert Molokie, Donald Lavelle, Michel Gowhari, Michael Pacini, Lani Krauz, Johara Hassan, Vinzon Ibanez, Maria A. Ruiz, Kwok Peng Ng, Philip Woost, Tomas Radivoyevitch, Daisy Pacelli, Sherry Fada, Matthew Rump, Matthew Hsieh, John F. Tisdale, James Jacobberger, Mitch Phelps, James Douglas Engel, Santhosh Saraf, Lewis L. Hsu, Victor Gordeuk, Joseph DeSimone, Yogen Saunthararajah
    更新日期:2017-09-07
  • Women’s and men’s reports of past-year prevalence of intimate partner violence and rape and women’s risk factors for intimate partner violence: A multicountry cross-sectional study in Asia and the Pacific
    PLOS Med. (IF 11.862) Pub Date : 2017-09-05
    Rachel Jewkes, Emma Fulu, Ruchira Tabassam Naved, Esnat Chirwa, Kristin Dunkle, Regine Haardörfer, Claudia Garcia-Moreno, on behalf of the UN Multi-country Study on Men and Violence Study Team
    更新日期:2017-09-06
  • Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study
    PLOS Med. (IF 11.862) Pub Date : 2017-08-29
    Nicholas M. Douglas, Jeanne Rini Poespoprodjo, Dewi Patriani, Michael J. Malloy, Enny Kenangalem, Paulus Sugiarto, Julie A. Simpson, Yati Soenarto, Nicholas M. Anstey, Ric N. Price
    更新日期:2017-08-30
  • Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts
    PLOS Med. (IF 11.862) Pub Date : 2017-08-22
    Diana L. Santos Ferreira, Dylan M. Williams, Antti J. Kangas, Pasi Soininen, Mika Ala-Korpela, George Davey Smith, Marjo-Riitta Jarvelin, Debbie A. Lawlor
    更新日期:2017-08-23
  • Antimicrobial resistance: The complex challenge of measurement to inform policy and the public
    PLOS Med. (IF 11.862) Pub Date : 2017-08-17
    Didier Wernli, Peter S. Jørgensen, Stephan Harbarth, Scott P. Carroll, Ramanan Laxminarayan, Nicolas Levrat, John-Arne Røttingen, Didier Pittet
    更新日期:2017-08-17
  • Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials
    PLOS Med. (IF 11.862) Pub Date : 2017-08-15
    Harsha Shanthanna, Ian Gilron, Manikandan Rajarathinam, Rizq AlAmri, Sriganesh Kamath, Lehana Thabane, Philip J. Devereaux, Mohit Bhandari
    更新日期:2017-08-15
  • Effectiveness of a brief behavioural intervention on psychological distress among women with a history of gender-based violence in urban Kenya: A randomised clinical trial
    PLOS Med. (IF 11.862) Pub Date : 2017-08-15
    Richard A. Bryant, Alison Schafer, Katie S. Dawson, Dorothy Anjuri, Caroline Mulili, Lincoln Ndogoni, Phiona Koyiet, Marit Sijbrandij, Jeannette Ulate, Melissa Harper Shehadeh, Dusan Hadzi-Pavlovic, Mark van Ommeren
    更新日期:2017-08-15
  • Pregnant and breastfeeding women: A priority population for HIV viral load monitoring
    PLOS Med. (IF 11.862) Pub Date : 2017-08-15
    Landon Myer, Shaffiq Essajee, Laura N. Broyles, D. Heather Watts, Maia Lesosky, Wafaa M. El-Sadr, Elaine J. Abrams
    更新日期:2017-08-15
  • Impact of fortified versus unfortified lipid-based supplements on morbidity and nutritional status: A randomised double-blind placebo-controlled trial in ill Gambian children
    PLOS Med. (IF 11.862) Pub Date : 2017-08-15
    Stefan A. Unger, Saikou Drammeh, Jahid Hasan, Kabiru Ceesay, Edrisa Sinjanka, Sainey Beyai, Bakary Sonko, Bai Lamin Dondeh, Anthony J. Fulford, Sophie E. Moore, Andrew M. Prentice
    更新日期:2017-08-15
  • Assessing the impact of healthcare research: A systematic review of methodological frameworks
    PLOS Med. (IF 11.862) Pub Date : 2017-08-09
    Samantha Cruz Rivera, Derek G. Kyte, Olalekan Lee Aiyegbusi, Thomas J. Keeley, Melanie J. Calvert
    更新日期:2017-08-10
  • Malaria, malnutrition, and birthweight: A meta-analysis using individual participant data
    PLOS Med. (IF 11.862) Pub Date : 2017-08-08
    Jordan E. Cates, Holger W. Unger, Valerie Briand, Nadine Fievet, Innocent Valea, Halidou Tinto, Umberto D’Alessandro, Sarah H. Landis, Seth Adu-Afarwuah, Kathryn G. Dewey, Feiko O. ter Kuile, Meghna Desai, Stephanie Dellicour, Peter Ouma, Julie Gutman, Martina Oneko, Laurence Slutsker, Dianne J. Terlouw, Simon Kariuki, John Ayisi, Mwayiwawo Madanitsa, Victor Mwapasa, Per Ashorn, Kenneth Maleta, Ivo Mueller, Danielle Stanisic, Christentze Schmiegelow, John P. A. Lusingu, Anna Maria van Eijk, Melissa Bauserman, Linda Adair, Stephen R. Cole, Daniel Westreich, Steven Meshnick, Stephen Rogerson
    更新日期:2017-08-09
  • Harmonization of community health worker programs for HIV: A four-country qualitative study in Southern Africa
    PLOS Med. (IF 11.862) Pub Date : 2017-08-08
    Jan-Walter De Neve, Henri Garrison-Desany, Kathryn G. Andrews, Nour Sharara, Chantelle Boudreaux, Roopan Gill, Pascal Geldsetzer, Maria Vaikath, Till Bärnighausen, Thomas J. Bossert
    更新日期:2017-08-09
  • Evaluation of novel computerized tomography scoring systems in human traumatic brain injury: An observational, multicenter study
    PLOS Med. (IF 11.862) Pub Date : 2017-08-03
    Eric Peter Thelin, David W. Nelson, Juho Vehviläinen, Harriet Nyström, Riku Kivisaari, Jari Siironen, Mikael Svensson, Markus B. Skrifvars, Bo-Michael Bellander, Rahul Raj
    更新日期:2017-08-04
  • Patient-reported outcomes and survival in multiple sclerosis: A 10-year retrospective cohort study using the Multiple Sclerosis Impact Scale–29
    PLOS Med. (IF 11.862) Pub Date : 2017-07-10
    Joel Raffel, Alison Wallace, Djordje Gveric, Richard Reynolds, Tim Friede, Richard Nicholas

    Background There is increasing emphasis on using patient-reported outcomes (PROs) to complement traditional clinical outcomes in medical research, including in multiple sclerosis (MS). Research, particularly in oncology and heart failure, has shown that PROs can be prognostic of hard clinical endpoints such as survival time (time from study entry until death). However, unlike in oncology or cardiology, it is unknown whether PROs are associated with survival time in neurological diseases. The Multiple Sclerosis Impact Scale–29 (MSIS-29) is a PRO sensitive to short-term change in MS, with questions covering both physical and psychological quality of life. This study aimed to investigate whether MSIS-29 scores can be prognostic for survival time in MS, using a large observational cohort of people with MS. Methods and findings From 15 July 2004 onwards, MSIS-29 questionnaires were completed by people with MS registered with the MS Society Tissue Bank (n = 2,126, repeated 1 year later with n = 872 of the original respondents). By 2014, 264 participants (12.4%) had died. Higher baseline MSIS-29 physical (MSIS-29-PHYS) score was associated with reduced survival time (subgroup with highest scores versus subgroup with lowest scores: hazard ratio [HR] 5.7, 95% CI 3.1–10.5, p < 0.001). Higher baseline MSIS-29 psychological score was also associated with reduced survival time (subgroup with highest scores versus subgroup with lowest scores: HR 2.8, 95% CI 1.8–4.4, p < 0.001). In those with high baseline MSIS-29 scores, mortality risk was even greater if the MSIS-29 score worsened over 1 year (HR 2.3, 95% CI 1.2–4.4, p = 0.02). MSIS-29-PHYS scores were associated with survival time independent of age, sex, and patient-reported Expanded Disability Status Scale score in a Cox regression analysis (per 1-SD increase in MSIS-29-PHYS score: HR 1.8, 95% CI 1.1–2.9, p = 0.03). A limitation of the study is that this cohort had high baseline age and disability levels; the prognostic value of MSIS-29 for survival time at earlier disease stages requires further investigation. Conclusions This study reports that PROs can be prognostic for hard clinical outcomes in neurological disease, and supports PROs as a meaningful clinical outcome for use in research and clinical settings.

    更新日期:2017-08-03
  • Cancer trials in sub-Saharan Africa: Aligning research and care
    PLOS Med. (IF 11.862) Pub Date : 2017-07-10
    Satish Gopal

    更新日期:2017-08-03
  • Validation of the sensitivity of the National Emergency X-Radiography Utilization Study (NEXUS) Head computed tomographic (CT) decision instrument for selective imaging of blunt head injury patients: An observational study
    PLOS Med. (IF 11.862) Pub Date : 2017-07-11
    William R. Mower, Malkeet Gupta, Robert Rodriguez, Gregory W. Hendey

    Background Clinicians, afraid of missing intracranial injuries, liberally obtain computed tomographic (CT) head imaging in blunt trauma patients. Prior work suggests that clinical criteria (National Emergency X-Radiography Utilization Study [NEXUS] Head CT decision instrument [DI]) can reliably identify patients with important injuries, while excluding injury, and the need for imaging in many patients. Validating this DI requires confirmation of the hypothesis that the lower 95% confidence limit for its sensitivity in detecting serious injury exceeds 99.0%. A secondary goal of the study was to complete an independent validation and comparison of the Canadian and NEXUS Head CT rules among the subgroup of patients meeting the inclusion and exclusion criteria. Methods and findings We conducted a prospective observational study of the NEXUS Head CT DI in 4 hospital emergency departments between April 2006 and December 2015. Implementation of the rule requires that patients satisfy 8 criteria to achieve “low-risk” classification. Patients are excluded from “low-risk” classification and assigned “high-risk” status if they fail to meet 1 or more criteria. We examined the instrument’s performance in assigning “high-risk” status to patients requiring neurosurgical intervention among a cohort of 11,770 blunt head injury patients. The NEXUS Head CT DI assigned high-risk status to 420 of 420 patients requiring neurosurgical intervention (sensitivity, 100.0% [95% confidence interval [CI]: 99.1%–100.0%]). The instrument assigned low-risk status to 2,823 of 11,350 patients who did not require neurosurgical intervention (specificity, 24.9% [95% CI: 24.1%–25.7%]). None of the 2,823 low-risk patients required neurosurgical intervention (negative predictive value [NPV], 100.0% [95% CI: 99.9%–100.0%]). The DI assigned high-risk status to 759 of 767 patients with significant intracranial injuries (sensitivity, 99.0% [95% CI: 98.0%–99.6%]). The instrument assigned low-risk status to 2,815 of 11,003 patients who did not have significant injuries (specificity, 25.6% [95% CI: 24.8%–26.4%]). Significant injuries were absent in 2,815 of the 2,823 patients assigned low-risk status (NPV, 99.7% [95% CI: 99.4%–99.9%]). Of our patients, 7,759 (65.9%) met the inclusion and exclusion criteria of the Canadian Head CT rule, including 111 patients (1.43%) who required neurosurgical intervention and 306 (3.94%) who had significant intracranial injuries. In our study, the Canadian criteria for neurosurgical intervention identified 108 of 111 patients requiring neurosurgical intervention to yield a sensitivity of 97.3% (95% CI: 92.3%–99.4%) and exhibited a specificity of 58.8% (95% CI: 57.7%–59.9%). The NEXUS rule, when applied to this same cohort, identified all 111 patients requiring neurosurgical intervention, yielding a sensitivity of 100% (95% CI: 96.7%–100.0%) with a specificity of 32.6% (95% CI: 31.5%–33.6%). Our study found that the Canadian medium-risk factors identified 301 of 306 patients with significant injuries (sensitivity = 98.4%; 95% CI: 96.2%–99.5%), while the NEXUS rule identified 299 of these patients (sensitivity = 97.7%; 95% CI: 95.3%–99.1%). In our study, the Canadian medium-risk rule exhibited a specificity of 12.3% (95% CI: 11.6%–13.1%), while the NEXUS rule exhibited a specificity of 33.3% (95% CI: 32.3%–34.4%). Limitations of the study may arise from application of the rule by different clinicians in different environments. Clinicians may vary in their interpretation and application of the instrument’s criteria and risk assignment and may also vary in deciding which patients require intervention. The instrument’s specificity is also subject to spectrum bias and may change with variations in the proportion of “low-risk” patients seen in other centers. Conclusions The NEXUS Head CT DI reliably identifies blunt trauma patients who require head CT imaging and could significantly reduce the use of CT imaging.

    更新日期:2017-08-03
  • Years of life lost due to traumatic brain injury in Europe: A cross-sectional analysis of 16 countries
    PLOS Med. (IF 11.862) Pub Date : 2017-07-11
    Marek Majdan, Dominika Plancikova, Andrew Maas, Suzanne Polinder, Valery Feigin, Alice Theadom, Martin Rusnak, Alexandra Brazinova, Juanita Haagsma

    Introduction Traumatic brain injuries (TBIs) are a major public health, medical, and societal challenge globally. They present a substantial burden to victims, their families, and the society as a whole. Although indicators such as incidence or death rates provide insight into the occurrence and outcome of TBIs in various populations, they fail to quantify the full extent of their public health and societal impact. Measures such as years of life lost (YLLs), which quantifies the number of years of life lost because the person dies prematurely due to a disease or injury, should be employed to better quantify the population impact. The aim of this study was to provide an in-depth analysis of the burden of deaths due to TBI by calculating TBI-specific YLLs in 16 European countries, analyzing their main causes and demographic patterns, using data extracted from death certificates under unified guidelines and collected in a standardized manner. Methods and findings A population-wide, cross-sectional epidemiological study was conducted in 16 European countries to estimate TBI YLLs for the year 2013. The data used for all analyses in this study were acquired from the statistical office of the European Union (Eurostat). A specifically tailored dataset of micro-level data was provided that listed the external cause of death (International Classification of Diseases–10th Revision [ICD-10] codes V01–Y98), the specific nature of injury (ICD-10 codes S00–T98), the age at death, and sex for each death. Overall number of TBI YLLs, crude and age-standardized TBI YLL rates, and TBI YLLs per case were calculated stratified for country, sex, and age. Pooled analyses were performed in order to estimate summary age-standardized rates of TBI YLLs. In order to evaluate the relative importance of TBI in the context of all injuries, proportions of TBI YLLs out of overall injury YLLs were calculated. The total number of TBI YLLs was estimated by extrapolating the pooled crude rate of TBI YLLs in the 16 analyzed countries to the total population of the 28 member states of the EU (EU-28). We found that a total of 17,049 TBI deaths occurred in 2013 in the 16 analyzed countries. These translated into a total of 374,636 YLLs. The pooled age-standardized rate of YLLs per 100,000 people per year was 259.1 (95% CI: 205.8 to 312.3) overall, 427.5 (95% CI: 290.0 to 564.9) in males, and 105.4 (95% CI: 89.1 to 121.6) in females. Males contributed substantially more to TBI YLLs than females (282,870 YLLs, 76% of all TBI YLLs), which translated into a rate ratio of 3.24 (95% CI: 3.22 to 3.27). Each TBI death was on average associated with 24.3 (95% CI: 22.0 to 26.6) YLLs overall, 25.6 (95% CI: 23.4 to 27.8) in males and 20.9 (17.9 to 24.0) in females. Falls and traffic crashes were the most common external causes of TBI YLLs. TBI contributed on average 41% (44% in males and 34% in females) to overall injury YLLs. Extrapolating our findings, about 1.3 million YLLs were attributable to TBI in the EU-28 in 2013 overall, 1.1 million in males and 271,000 in females. This study is based on administratively collected data from 16 countries, and despite the efforts to harmonize them to the greatest possible extent, there may be differences in coding practices or reporting between countries. If present, these would be inherited into our findings without our ability to control for them. The extrapolation of the pooled rates from the 16 countries to the EU-28 should be interpreted with caution. Conclusions Our study showed that TBI-related deaths and YLLs have a substantial impact at the individual and population level in Europe and present an important societal and economic burden that must not be overlooked. We provide information valuable for policy-makers, enabling them to evaluate and plan preventive activities and resource allocation, and to formulate and implement strategic decisions. In addition, our results can serve as a basis for analyzing the overall burden of TBI in the population.

    更新日期:2017-08-03
  • Trends in traumatic brain injury mortality in China, 2006–2013: A population-based longitudinal study
    PLOS Med. (IF 11.862) Pub Date : 2017-07-11
    Peixia Cheng, Peng Yin, Peishan Ning, Lijun Wang, Xunjie Cheng, Yunning Liu, David C. Schwebel, Jiangmei Liu, Jinlei Qi, Guoqing Hu, Maigeng Zhou

    Background Traumatic brain injury (TBI) is a significant global public health problem, but has received minimal attention from researchers and policy-makers in low- and middle-income countries (LMICs). Epidemiological evidence of TBI morbidity and mortality is absent at the national level for most LMICs, including China. Using data from China’s Disease Surveillance Points (DSPs) system, we conducted a population-based longitudinal analysis to examine TBI mortality, and mortality differences by sex, age group, location (urban/rural), and external cause of injury, from 1 January 2006 to 31 December 2013 in China. Method and findings Mortality data came from the national DSPs system of China, which has coded deaths using the International Classification of Diseases–10th Revision (ICD-10) since 2004. Crude and age-standardized mortality with 95% CIs were estimated using the census population in 2010 as a reference population. The Cochran–Armitage trend test was used to examine the significance of trends in mortality from 2006 to 2013. Negative binomial models were used to examine the associations of TBI mortality with location, sex, and age group. Subgroup analysis was performed by external cause of TBI. We found the following: (1) Age-adjusted TBI mortality increased from 13.23 per 100,000 population in 2006 to 17.06 per 100,000 population in 2008 and then began to fall slightly. In 2013, age-adjusted TBI mortality was 12.99 per 100,000 population (SE = 0.13). (2) Compared to females and urban residents, males and rural residents had higher TBI mortality risk, with adjusted mortality rate ratios of 2.57 and 1.71, respectively. TBI mortality increased substantially with older age. (3) Motor vehicle crashes and falls were the 2 leading causes of TBI mortality between 2006 and 2013. TBI deaths from motor vehicle crashes in children aged 0–14 years and adults aged 65 years and older were most often in pedestrians, and motorcyclists were the first or second leading category of road user for the other age groups. (4) TBI mortality attributed to motor vehicle crashes increased for pedestrians and motorcyclists in all 7 age groups from 2006 to 2013. Our analysis was limited by the availability and quality of data in the DSPs dataset, including lack of injury-related socio-economic factors, policy factors, and individual and behavioral factors. The dataset also may be incomplete in TBI death recording or contain misclassification of mortality data. Conclusions TBI constitutes a serious public health threat in China. Further studies should explore the reasons for the particularly high risk of TBI mortality among particular populations, as well as the reasons for recent increases in certain subgroups, and should develop solutions to address these challenges. Interventions proven to work in other cultures should be introduced and implemented nationwide. Examples of these in the domain of motor vehicle crashes include policy change and enforcement of laws concerning helmet use for motorcyclists and bicyclists, car seat and booster seat use for child motor vehicle passengers, speed limit and drunk driving laws, and alcohol ignition interlock use. Examples to prevent falls, especially among elderly individuals, include exercise programs, home modification to reduce fall risk, and multifaceted interventions to prevent falls in all age groups.

    更新日期:2017-08-03
  • Community and health system intervention to reduce disrespect and abuse during childbirth in Tanga Region, Tanzania: A comparative before-and-after study
    PLOS Med. (IF 11.862) Pub Date : 2017-07-11
    Stephanie A. Kujawski, Lynn P. Freedman, Kate Ramsey, Godfrey Mbaruku, Selemani Mbuyita, Wema Moyo, Margaret E. Kruk

    Background Abusive treatment of women during childbirth has been documented in low-resource countries and is a deterrent to facility utilization for delivery. Evidence for interventions to address women’s poor experience is scant. We assessed a participatory community and health system intervention to reduce the prevalence of disrespect and abuse during childbirth in Tanzania. Methods and findings We used a comparative before-and-after evaluation design to test the combined intervention to reduce disrespect and abuse. Two hospitals in Tanga Region, Tanzania were included in the study, 1 randomly assigned to receive the intervention. Women who delivered at the study facilities were eligible to participate and were recruited upon discharge. Surveys were conducted at baseline (December 2011 through May 2012) and after the intervention (March through September 2015). The intervention consisted of a client service charter and a facility-based, quality-improvement process aimed to redefine norms and practices for respectful maternity care. The primary outcome was any self-reported experiences of disrespect and abuse during childbirth. We used multivariable logistic regression to estimate a difference-in-difference model. At baseline, 2,085 women at the 2 study hospitals who had been discharged from the maternity ward after delivery were invited to participate in the survey. Of these, 1,388 (66.57%) agreed to participate. At endline, 1,680 women participated in the survey (72.29% of those approached). The intervention was associated with a 66% reduced odds of a woman experiencing disrespect and abuse during childbirth (odds ratio [OR]: 0.34, 95% CI: 0.21–0.58, p < 0.0001). The biggest reductions were for physical abuse (OR: 0.22, 95% CI: 0.05–0.97, p = 0.045) and neglect (OR: 0.36, 95% CI: 0.19–0.71, p = 0.003). The study involved only 2 hospitals in Tanzania and is thus a proof-of-concept study. Future, larger-scale research should be undertaken to evaluate the applicability of this approach to other settings. Conclusions After implementation of the combined intervention, the likelihood of women’s reports of disrespectful treatment during childbirth was substantially reduced. These results were observed nearly 1 year after the end of the project’s facilitation of implementation, indicating the potential for sustainability. The results indicate that a participatory community and health system intervention designed to tackle disrespect and abuse by changing the norms and standards of care is a potential strategy to improve the treatment of women during childbirth at health facilities. The trial is registered on the ISRCTN Registry, ISRCTN 48258486. Trial registration ISRCTN Registry, ISRCTN 48258486

    更新日期:2017-08-03
  • Leveraging peer-based support to facilitate HIV care in Kenya
    PLOS Med. (IF 11.862) Pub Date : 2017-07-14
    Rakhi Karwa, Mercy Maina, Timothy Mercer, Benson Njuguna, Juddy Wachira, Celia Ngetich, Fatma Some, Beatrice Jakait, Regina K. Owino, Adrian Gardner, Sonak Pastakia

    更新日期:2017-08-03
  • Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study
    PLOS Med. (IF 11.862) Pub Date : 2017-07-17
    Claudia P. Cabrera, Joanna Manson, Joanna M. Shepherd, Hew D. Torrance, David Watson, M. Paula Longhi, Mimoza Hoti, Minal B. Patel, Michael O’Dwyer, Sussan Nourshargh, Daniel J. Pennington, Michael R. Barnes, Karim Brohi

    Background Severe trauma induces a widespread response of the immune system. This “genomic storm” can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS. Methods and findings We performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ≥ 25) at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ≤ 4). We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK) cells, with underexpression of T- and B cell responses. In the transcriptome cohort, 20 critically injured patients later developed MODS. Compared with the 16 patients who did not develop MODS (NoMODS), maximal differential expression was seen within the hyperacute window. In MODS versus NoMODS, 363 genes were differentially expressed on admission, compared to only 33 at 24 hours postinjury. MODS transcripts differentially expressed in the hyperacute window showed enrichment among diseases and biological functions associated with cell survival and organismal death rather than inflammatory pathways. There was differential up-regulation of NK cell signalling pathways and markers in patients who would later develop MODS, with down-regulation of neutrophil deconvolution markers. This study is limited by its sample size, precluding more detailed analyses of drivers of the hyperacute response and different MODS phenotypes, and requires validation in other critically injured cohorts. Conclusions In this study, we showed how the hyperacute postinjury time window contained a focused, specific signature of the response to critical injury that led to widespread genomic activation. A transcriptomic signature for later development of MODS was present in this hyperacute window; it showed a strong signal for cell death and survival pathways and implicated NK cells and neutrophil populations in this differential response.

    更新日期:2017-08-03
  • Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study
    PLOS Med. (IF 11.862) Pub Date : 2017-07-18
    Jon Hazeldine, David N. Naumann, Emma Toman, David Davies, Jonathan R. B. Bishop, Zhangjie Su, Peter Hampson, Robert J. Dinsdale, Nicholas Crombie, Niharika Arora Duggal, Paul Harrison, Antonio Belli, Janet M. Lord

    Background Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS). Methods and findings The immune and inflammatory response to trauma was analysed in 89 adult trauma patients (mean age 41 years, range 18–90 years, 75 males) with a mean injury severity score (ISS) of 24 (range 9–66), from whom blood samples were acquired within 1 hour of injury (mean time to sample 42 minutes, range 17–60 minutes). Within minutes of trauma, a comprehensive leukocytosis, elevated serum pro- and anti-inflammatory cytokines, and evidence of innate cell activation that included neutrophil extracellular trap generation and elevated surface expression of toll-like receptor 2 and CD11b on monocytes and neutrophils, respectively, were observed. Features consistent with immune compromise were also detected, notably elevated numbers of immune suppressive CD16BRIGHT CD62LDIM neutrophils (82.07 x 106/l ± 18.94 control versus 1,092 x 106/l ± 165 trauma, p < 0.0005) and CD14+HLA-DRlow/− monocytes (34.96 x 106/l ± 4.48 control versus 95.72 x 106/l ± 8.0 trauma, p < 0.05) and reduced leukocyte cytokine secretion in response to lipopolysaccharide stimulation. Exploratory analysis via binary logistic regression found a potential association between absolute natural killer T (NKT) cell numbers and the subsequent development of MODS. Study limitations include the relatively small sample size and the absence of data relating to adaptive immune cell function. Conclusions Our study highlighted the dynamic and complex nature of the immune response to trauma, with immune alterations consistent with both activation and suppression evident within 1 hour of injury. The relationship of these changes, especially in NKT cell numbers, to patient outcomes such as MODS warrants further investigation.

    更新日期:2017-08-03
  • Prescription medicine use by pedestrians and the risk of injurious road traffic crashes: A case-crossover study
    PLOS Med. (IF 11.862) Pub Date : 2017-07-18
    Mélanie Née, Marta Avalos, Audrey Luxcey, Benjamin Contrand, Louis-Rachid Salmi, Annie Fourrier-Réglat, Blandine Gadegbeku, Emmanuel Lagarde, Ludivine Orriols

    Background While some medicinal drugs have been found to affect driving ability, no study has investigated whether a relationship exists between these medicines and crashes involving pedestrians. The aim of this study was to explore the association between the use of medicinal drugs and the risk of being involved in a road traffic crash as a pedestrian. Methods and findings Data from 3 French nationwide databases were matched. We used the case-crossover design to control for time-invariant factors by using each case as its own control. To perform multivariable analysis and limit false-positive results, we implemented a bootstrap version of Lasso. To avoid the effect of unmeasured time-varying factors, we varied the length of the washout period from 30 to 119 days before the crash. The matching procedure led to the inclusion of 16,458 pedestrians involved in an injurious road traffic crash from 1 July 2005 to 31 December 2011. We found 48 medicine classes with a positive association with the risk of crash, with median odds ratios ranging from 1.12 to 2.98. Among these, benzodiazepines and benzodiazepine-related drugs, antihistamines, and anti-inflammatory and antirheumatic drugs were among the 10 medicines most consumed by the 16,458 pedestrians. Study limitations included slight overrepresentation of pedestrians injured in more severe crashes, lack of information about self-medication and the use of over-the-counter drugs, and lack of data on amount of walking. Conclusions Therapeutic classes already identified as impacting the ability to drive, such as benzodiazepines and antihistamines, are also associated with an increased risk of pedestrians being involved in a road traffic crash. This study on pedestrians highlights the necessity of improving awareness of the effect of these medicines on this category of road user.

    更新日期:2017-08-03
  • Cerebrovascular pressure reactivity monitoring using wavelet analysis in traumatic brain injury patients: A retrospective study
    PLOS Med. (IF 11.862) Pub Date : 2017-07-25
    Xiuyun Liu, Joseph Donnelly, Marek Czosnyka, Marcel J. H. Aries, Ken Brady, Danilo Cardim, Chiara Robba, Manuel Cabeleira, Dong-Joo Kim, Christina Haubrich, Peter J. Hutchinson, Peter Smielewski

    Background After traumatic brain injury (TBI), the ability of cerebral vessels to appropriately react to changes in arterial blood pressure (pressure reactivity) is impaired, leaving patients vulnerable to cerebral hypo- or hyperperfusion. Although, the traditional pressure reactivity index (PRx) has demonstrated that impaired pressure reactivity is associated with poor patient outcome, PRx is sometimes erratic and may not be reliable in various clinical circumstances. Here, we introduce a more robust transform-based wavelet pressure reactivity index (wPRx) and compare its performance with the widely used traditional PRx across 3 areas: its stability and reliability in time, its ability to give an optimal cerebral perfusion pressure (CPPopt) recommendation, and its relationship with patient outcome. Methods and findings Five hundred and fifteen patients with TBI admitted in Addenbrooke’s Hospital, United Kingdom (March 23rd, 2003 through December 9th, 2014), with continuous monitoring of arterial blood pressure (ABP) and intracranial pressure (ICP), were retrospectively analyzed to calculate the traditional PRx and a novel wavelet transform-based wPRx. wPRx was calculated by taking the cosine of the wavelet transform phase-shift between ABP and ICP. A time trend of CPPopt was calculated using an automated curve-fitting method that determined the cerebral perfusion pressure (CPP) at which the pressure reactivity (PRx or wPRx) was most efficient (CPPopt_PRx and CPPopt_wPRx, respectively). There was a significantly positive relationship between PRx and wPRx (r = 0.73), and wavelet wPRx was more reliable in time (ratio of between-hour variance to total variance, wPRx 0.957 ± 0.0032 versus PRx and 0.949 ± 0.047 for PRx, p = 0.002). The 2-hour interval standard deviation of wPRx (0.19 ± 0.07) was smaller than that of PRx (0.30 ± 0.13, p < 0.001). wPRx performed better in distinguishing between mortality and survival (the area under the receiver operating characteristic [ROC] curve [AUROC] for wPRx was 0.73 versus 0.66 for PRx, p = 0.003). The mean difference between the patients’ CPP and their CPPopt was related to outcome for both calculation methods. There was a good relationship between the 2 CPPopts (r = 0.814, p < 0.001). CPPopt_wPRx was more stable than CPPopt_PRx (within patient standard deviation 7.05 ± 3.78 versus 8.45 ± 2.90; p < 0.001). Key limitations include that this study is a retrospective analysis and only compared wPRx with PRx in the cohort of patients with TBI. Prior prospective validation is required to better assess clinical utility of this approach. Conclusions wPRx offers several advantages to the traditional PRx: it is more stable in time, it yields a more consistent CPPopt recommendation, and, importantly, it has a stronger relationship with patient outcome. The clinical utility of wPRx should be explored in prospective studies of critically injured neurological patients.

    更新日期:2017-08-03
  • A comparison of Selective Aortic Arch Perfusion and Resuscitative Endovascular Balloon Occlusion of the Aorta for the management of hemorrhage-induced traumatic cardiac arrest: A translational model in large swine
    PLOS Med. (IF 11.862) Pub Date : 2017-07-25
    Ed B. G. Barnard, James E. Manning, Jason E. Smith, Jason M. Rall, Jennifer M. Cox, James D. Ross

    Background Survival rates remain low after hemorrhage-induced traumatic cardiac arrest (TCA). Noncompressible torso hemorrhage (NCTH) is a major cause of potentially survivable trauma death. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) at the thoracic aorta (Zone 1) can limit subdiaphragmatic blood loss and allow for IV fluid resuscitation when intrinsic cardiac activity is still present. Selective Aortic Arch Perfusion (SAAP) combines thoracic aortic balloon hemorrhage control with intra-aortic oxygenated perfusion to achieve return of spontaneous circulation (ROSC) when cardiac arrest has occurred. Methods and findings Male Yorkshire Landrace cross swine (80.0 ± 6.0 kg) underwent anesthesia, instrumentation for monitoring, and splenectomy. TCA was induced by laparoscopic liver lobe resection combined with arterial catheter blood withdrawal to achieve a sustained systolic blood pressure <10 mmHg, cardiac arrest. After 3 min of arrest, swine were allocated to one of three interventions: (1) REBOA plus 4 units of IV fresh whole blood (FWB), (2) SAAP with oxygenated lactated Ringer’s (LR), 1,600 mL/2 min, or (3) SAAP with oxygenated FWB 1,600 mL/2 min. Primary endpoint was survival to the end of 60 min of resuscitation, a simulated prehospital phase. Thirty animals were allocated to 3 groups (10 per group)—5 protocol exclusions resulted in a total of 35 animals being used. Baseline measurements and time to cardiac arrest were not different amongst groups. ROSC was achieved in 0/10 (0%, 95% CI 0.00–30.9) REBOA, 6/10 (60%, 95% CI 26.2–87.8) SAAP-LR and 10/10 (100%, 95% CI 69.2–100.0) SAAP-FWB animals, p < 0.001. Survival to end of simulated 60-minute prehospital resuscitation was 0/10 (0%, 95% CI 0.00–30.9) for REBOA, 1/10 (10%, 95% CI 0.25–44.5) for SAAP-LR and 9/10 (90%, 95% CI 55.5–99.7) for SAAP-FWB, p < 0.001. Total FWB infusion volume was similar for REBOA (2,452 ± 0 mL) and SAAP-FWB (2,250 ± 594 mL). This study was undertaken in laboratory conditions, and as such may have practical limitations when applied clinically. Cardiac arrest in this study was defined by intra-aortic pressure monitoring that is not feasible in clinical practice, and as such limits the generalizability of findings. Clinical trials are needed to determine if the beneficial effects of SAAP-FWB observed in this laboratory study will translate into improved survival in clinical practice. Conclusions SAAP conferred a superior short-term survival over REBOA in this large animal model of hemorrhage-induced traumatic cardiac arrest with NCTH. SAAP using an oxygen-carrying perfusate was more effective in this study than non-oxygen carrying solutions in TCA. SAAP can effect ROSC from hemorrhage-induced electrocardiographic asystole in large swine.

    更新日期:2017-08-03
  • Temporal profile of intracranial pressure and cerebrovascular reactivity in severe traumatic brain injury and association with fatal outcome: An observational study
    PLOS Med. (IF 11.862) Pub Date : 2017-07-25
    Hadie Adams, Joseph Donnelly, Marek Czosnyka, Angelos G. Kolias, Adel Helmy, David K. Menon, Peter Smielewski, Peter J. Hutchinson

    Background Both intracranial pressure (ICP) and the cerebrovascular pressure reactivity represent the dysregulation of pathways directly involved in traumatic brain injury (TBI) pathogenesis and have been used to inform clinical management. However, how these parameters evolve over time following injury and whether this evolution has any prognostic importance have not been studied. Methods and findings We analysed the temporal profile of ICP and pressure reactivity index (PRx), examined their relation to TBI-specific mortality, and determined if the prognostic relevance of these parameters was affected by their temporal profile using mixed models for repeated measures of ICP and PRx for the first 240 hours from the time of injury. A total of 601 adults with TBI, admitted between September 2002 to January 2016, and with high-resolution continuous monitoring from a single centre, were studied. At 6 months postinjury, 133 (19%) patients had a fatal outcome; of those, 88 (78%) died from nonsurvivable TBI or brain death. The difference in mean ICP between those with a fatal outcome and functional survivors was only significant for the first 168 hours after injury (all p < 0.05). For PRx, those patients with a fatal outcome also had a higher (more impaired) PRx throughout the first 120 hours after injury (all p < 0.05). The separation of ICP and PRx was greatest in the first 72 hours after injury. Mixed models demonstrated that the explanatory power of the PRx decreases over time; therefore, the prognostic weight assigned to PRx should similarly decrease. However, the ability of ICP to predict a fatal outcome remained relatively stable over time. As control of ICP is the central purpose of TBI management, it is likely that some of the information that is reflected in the natural history of ICP changes is no longer apparent because of therapeutic intervention. Conclusions We demonstrated the temporal evolution of ICP and PRx and their relationship with fatal outcome, indicating a potential early prognostic and therapeutic window. The combination of dynamic monitoring variables and their time profile improved prediction of outcome. Therefore, time-driven dynamic modelling of outcome in patients with severe TBI may allow for more accurate and clinically useful prediction models. Further research is needed to confirm and expand on these findings.

    更新日期:2017-08-03
  • Ultrasound non-invasive measurement of intracranial pressure in neurointensive care: A prospective observational study
    PLOS Med. (IF 11.862) Pub Date : 2017-07-25
    Chiara Robba, Danilo Cardim, Tamara Tajsic, Justine Pietersen, Michael Bulman, Joseph Donnelly, Andrea Lavinio, Arun Gupta, David K. Menon, Peter J. A. Hutchinson, Marek Czosnyka

    Background The invasive nature of the current methods for monitoring of intracranial pressure (ICP) has prevented their use in many clinical situations. Several attempts have been made to develop methods to monitor ICP non-invasively. The aim of this study is to assess the relationship between ultrasound-based non-invasive ICP (nICP) and invasive ICP measurement in neurocritical care patients. Methods and findings This was a prospective, single-cohort observational study of patients admitted to a tertiary neurocritical care unit. Patients with brain injury requiring invasive ICP monitoring were considered for inclusion. nICP was assessed using optic nerve sheath diameter (ONSD), venous transcranial Doppler (vTCD) of straight sinus systolic flow velocity (FVsv), and methods derived from arterial transcranial Doppler (aTCD) on the middle cerebral artery (MCA): MCA pulsatility index (PIa) and an estimator based on diastolic flow velocity (FVd). A total of 445 ultrasound examinations from 64 patients performed from 1 January to 1 November 2016 were included. The median age of the patients was 53 years (range 37–64). Median Glasgow Coma Scale at admission was 7 (range 3–14), and median Glasgow Outcome Scale was 3 (range 1–5). The mortality rate was 20%. ONSD and FVsv demonstrated the strongest correlation with ICP (R = 0.76 for ONSD versus ICP; R = 0.72 for FVsv versus ICP), whereas PIa and the estimator based on FVd did not correlate with ICP significantly. Combining the 2 strongest nICP predictors (ONSD and FVsv) resulted in an even stronger correlation with ICP (R = 0.80). The ability to detect intracranial hypertension (ICP ≥ 20 mm Hg) was highest for ONSD (area under the curve [AUC] 0.91, 95% CI 0.88–0.95). The combination of ONSD and FVsv methods showed a statistically significant improvement of AUC values compared with the ONSD method alone (0.93, 95% CI 0.90–0.97, p = 0.01). Major limitations are the heterogeneity and small number of patients included in this study, the need for specialised training to perform and interpret the ultrasound tests, and the variability in performance among different ultrasound operators. Conclusions Of the studied ultrasound nICP methods, ONSD is the best estimator of ICP. The novel combination of ONSD ultrasonography and vTCD of the straight sinus is a promising and easily available technique for identifying critically ill patients with intracranial hypertension.

    更新日期:2017-08-03
  • Same-day HIV testing with initiation of antiretroviral therapy versus standard care for persons living with HIV: A randomized unblinded trial
    PLOS Med. (IF 11.862) Pub Date : 2017-07-25
    Serena P. Koenig, Nancy Dorvil, Jessy G. Dévieux, Bethany L. Hedt-Gauthier, Cynthia Riviere, Mikerlyne Faustin, Kerlyne Lavoile, Christian Perodin, Alexandra Apollon, Limathe Duverger, Margaret L. McNairy, Kelly A. Hennessey, Ariadne Souroutzidis, Pierre-Yves Cremieux, Patrice Severe, Jean W. Pape

    Background Attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is high worldwide. We assessed whether same-day HIV testing and ART initiation improves retention and virologic suppression. Methods and findings We conducted an unblinded, randomized trial of standard ART initiation versus same-day HIV testing and ART initiation among eligible adults ≥18 years old with World Health Organization Stage 1 or 2 disease and CD4 count ≤500 cells/mm3. The study was conducted among outpatients at the Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic infections (GHESKIO) Clinic in Port-au-Prince, Haiti. Participants were randomly assigned (1:1) to standard ART initiation or same-day HIV testing and ART initiation. The standard group initiated ART 3 weeks after HIV testing, and the same-day group initiated ART on the day of testing. The primary study endpoint was retention in care 12 months after HIV testing with HIV-1 RNA <50 copies/ml. We assessed the impact of treatment arm with a modified intention-to-treat analysis, using multivariable logistic regression controlling for potential confounders. Between August 2013 and October 2015, 762 participants were enrolled; 59 participants transferred to other clinics during the study period, and were excluded as per protocol, leaving 356 in the standard and 347 in the same-day ART groups. In the standard ART group, 156 (44%) participants were retained in care with 12-month HIV-1 RNA <50 copies, and 184 (52%) had <1,000 copies/ml; 20 participants (6%) died. In the same-day ART group, 184 (53%) participants were retained with HIV-1 RNA <50 copies/ml, and 212 (61%) had <1,000 copies/ml; 10 (3%) participants died. The unadjusted risk ratio (RR) of being retained at 12 months with HIV-1 RNA <50 copies/ml was 1.21 (95% CI: 1.04, 1.38; p = 0.015) for the same-day ART group compared to the standard ART group, and the unadjusted RR for being retained with HIV-1 RNA <1,000 copies was 1.18 (95% CI: 1.04, 1.31; p = 0.012). The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain. Conclusions Same-day HIV testing and ART initiation is feasible and beneficial in this setting, as it improves retention in care with virologic suppression among patients with early clinical HIV disease. Trial registration This study is registered with ClinicalTrials.gov number NCT01900080

    更新日期:2017-08-03
  • Community burden of undiagnosed HIV infection among adolescents in Zimbabwe following primary healthcare-based provider-initiated HIV testing and counselling: A cross-sectional survey
    PLOS Med. (IF 11.862) Pub Date : 2017-07-25
    Victoria Simms, Ethel Dauya, Subathira Dakshina, Tsitsi Bandason, Grace McHugh, Shungu Munyati, Prosper Chonzi, Katharina Kranzer, Getrude Ncube, Collen Masimirembwa, Roslyn Thelingwani, Tsitsi Apollo, Richard Hayes, Helen A. Weiss, Rashida A. Ferrand

    Background Children living with HIV who are not diagnosed in infancy often remain undiagnosed until they present with advanced disease. Provider-initiated testing and counselling (PITC) in health facilities is recommended for high-HIV-prevalence settings, but it is unclear whether this approach is sufficient to achieve universal coverage of HIV testing. We aimed to investigate the change in community burden of undiagnosed HIV infection among older children and adolescents following implementation of PITC in Harare, Zimbabwe. Methods and findings Over the course of 2 years (January 2013–January 2015), 7 primary health clinics (PHCs) in southwestern Harare implemented optimised, opt-out PITC for all attendees aged 6–15 years. In February 2015–December 2015, we conducted a representative cross-sectional survey of 8–17-year-olds living in the 7 communities served by the study PHCs, who would have had 2 years of exposure to PITC. Knowledge of HIV status was ascertained through a caregiver questionnaire, and anonymised HIV testing was carried out using oral mucosal transudate (OMT) tests. After 1 participant taking antiretroviral therapy was observed to have a false negative OMT result, from July 2015 urine samples were obtained from all participants providing OMTs and tested for antiretroviral drugs to confirm HIV status. Children who tested positive through PITC were identified from among survey participants using gender, birthdate, and location. Of 7,146 children in 4,251 eligible households, 5,486 (76.8%) children in 3,397 households agreed to participate in the survey, and 141 were HIV positive. HIV prevalence was 2.6% (95% CI 2.2%–3.1%), and over a third of participants with HIV were undiagnosed (37.7%; 95% CI 29.8%–46.2%). Similarly, among the subsample of 2,643 (48.2%) participants with a urine test result, 34.7% of those living with HIV were undiagnosed (95% CI 23.5%–47.9%). Based on extrapolation from the survey sample to the community, we estimated that PITC over 2 years identified between 18% and 42% of previously undiagnosed children in the community. The main limitation is that prevalence of undiagnosed HIV was defined using a combination of 3 measures (OMT, self-report, and urine test), none of which were perfect. Conclusions Facility-based approaches are inadequate in achieving universal coverage of HIV testing among older children and adolescents. Alternative, community-based approaches are required to meet the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of diagnosing 90% of those living with HIV by 2020 in this age group.

    更新日期:2017-08-03
  • IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model
    PLOS Med. (IF 11.862) Pub Date : 2017-07-25
    Jing Xu, Jesse Guardado, Rosemary Hoffman, Hui Xu, Rami Namas, Yoram Vodovotz, Li Xu, Mostafa Ramadan, Joshua Brown, Heth R. Turnquist, Timothy R. Billiar

    Background The immunosuppression and immune dysregulation that follows severe injury includes type 2 immune responses manifested by elevations in interleukin (IL) 4, IL5, and IL13 early after injury. We hypothesized that IL33, an alarmin released early after tissue injury and a known regulator of type 2 immunity, contributes to the early type 2 immune responses after systemic injury. Methods and findings Blunt trauma patients admitted to the trauma intensive care unit of a level I trauma center were enrolled in an observational study that included frequent blood sampling. Dynamic changes in IL33 and soluble suppression of tumorigenicity 2 (sST2) levels were measured in the plasma and correlated with levels of the type 2 cytokines and nosocomial infection. Based on the observations in humans, mechanistic experiments were designed in a mouse model of resuscitated hemorrhagic shock and tissue trauma (HS/T). These experiments utilized wild-type C57BL/6 mice, IL33-/- mice, B6.C3(Cg)-Rorasg/sg mice deficient in group 2 innate lymphoid cells (ILC2), and C57BL/6 wild-type mice treated with anti-IL5 antibody. Severely injured human blunt trauma patients (n = 472, average injury severity score [ISS] = 20.2) exhibited elevations in plasma IL33 levels upon admission and over time that correlated positively with increases in IL4, IL5, and IL13 (P < 0.0001). sST2 levels also increased after injury but in a delayed manner compared with IL33. The increases in IL33 and sST2 were significantly greater in patients that developed nosocomial infection and organ dysfunction than similarly injured patients that did not (P < 0.05). Mechanistic studies were carried out in a mouse model of HS/T that recapitulated the early increase in IL33 and delayed increase in sST2 in the plasma (P < 0.005). These studies identified a pathway where IL33 induces ILC2 activation in the lung within hours of HS/T. ILC2 IL5 up-regulation induces further IL5 expression by CXCR2+ lung neutrophils, culminating in early lung injury. The major limitations of this study are the descriptive nature of the human study component and the impact of the potential differences between human and mouse immune responses to polytrauma. Also, the studies performed did not permit us to make conclusions about the impact of IL33 on pulmonary function. Conclusions These results suggest that IL33 may initiate early detrimental type 2 immune responses after trauma through ILC2 regulation of neutrophil IL5 production. This IL33–ILC2–IL5–neutrophil axis defines a novel regulatory role for ILC2 in acute lung injury that could be targeted in trauma patients prone to early lung dysfunction.

    更新日期:2017-08-03
  • Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicines
    PLOS Med. (IF 11.862) Pub Date : 2017-07-26
    Emilie Alirol, Teodora E. Wi, Manju Bala, Maria Luiza Bazzo, Xiang-Sheng Chen, Carolyn Deal, Jo-Anne R. Dillon, Ranmini Kularatne, Jutta Heim, Rob Hooft van Huijsduijnen, Edward W. Hook, Monica M. Lahra, David A. Lewis, Francis Ndowa, William M. Shafer, Liz Tayler, Kimberly Workowski, Magnus Unemo, Manica Balasegaram

    更新日期:2017-08-03
  • Childhood adiposity and risk of type 1 diabetes: A Mendelian randomization study
    PLOS Med. (IF 11.862) Pub Date : 2017-08-01
    J. C. Censin, Christoph Nowak, Nicholas Cooper, Peter Bergsten, John A. Todd, Tove Fall
    更新日期:2017-08-03
  • Identification of factors associated with stillbirth in the Indian state of Bihar using verbal autopsy: A population-based study
    PLOS Med. (IF 11.862) Pub Date : 2017-08-01
    Rakhi Dandona, G. Anil Kumar, Amit Kumar, Priyanka Singh, Sibin George, Mohammad Akbar, Lalit Dandona
    更新日期:2017-08-03
  • Gestational diabetes mellitus and interpregnancy weight change: A population-based cohort study
    PLOS Med. (IF 11.862) Pub Date : 2017-08-01
    L. M. Sorbye, R. Skjaerven, K. Klungsoyr, N. H. Morken
    更新日期:2017-08-03
  • IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model
    PLOS Med. (IF 11.862) Pub Date : 2017-07-25
    Jing Xu, Jesse Guardado, Rosemary Hoffman, Hui Xu, Rami Namas, Yoram Vodovotz, Li Xu, Mostafa Ramadan, Joshua Brown, Heth R. Turnquist, Timothy R. Billiar
    更新日期:2017-08-03
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Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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