Latest Articles Include:
- A Medical Journal for the World's Health Priorities
- PLoS Med 6(4):e1000072 (2009)
- The Millennium Development Goals Fail Poor Children: The Case for Equity-Adjusted Measures
- PLoS Med 6(4):e1000062 (2009)
- The Role of Rapid Diagnostic Tests in Managing Malaria
- PLoS Med 6(4):e1000063 (2009)
- Mapping the Spread of Malaria Drug Resistance
Anderson T - PLoS Med 6(4):e1000054 (2009)
- What Is the Significance of Unrecognized Non-Q-Wave Myocardial Infarction?
Chow CK - PLoS Med 6(4):e1000060 (2009)
Clara Kayei Chow discusses the clinical implications of a new study that sought to examine the frequency and prognosis of unrecognized non-Q-wave myocardial infarction. - Mapping Antibody Epitopes of the Avian H5N1 Influenza Virus
Yen HL Peiris JS - PLoS Med 6(4):e1000064 (2009)
Hui-Ling Yen and J. S. Malik Peiris discuss a study in PLoS Medicine that provides new information on the human antibody repertoire generated in response to H5N1 influenza virus infection. - Rapid Scale-Up of Antiretroviral Treatment in Ethiopia: Successes and System-Wide Effects
- PLoS Med 6(4):e1000056 (2009)
- A Compendium of Potential Biomarkers of Pancreatic Cancer
Harsha HC Kandasamy K Ranganathan P Rani S Ramabadran S Gollapudi S Balakrishnan L Dwivedi SB Telikicherla D Selvan LD Goel R Mathivanan S Marimuthu A Kashyap M Vizza RF Mayer RJ Decaprio JA Srivastava S Hanash SM Hruban RH Pandey A - PLoS Med 6(4):e1000046 (2009)
Akhilesh Pandey and colleagues describe a compendium of potential biomarkers that can be systematically validated by the pancreatic cancer community. - Global Health Actors Claim To Support Health System Strengthening—Is This Reality or Rhetoric?
- PLoS Med 6(4):e1000059 (2009)
- Tools for Assessing Neuropathic Pain
Cruccu G Truini A - PLoS Med 6(4):e1000045 (2009)
Giorgio Cruccu and Andrea Truini discuss a new pain assessment tool published in PLoS Medicine called Standardized Evaluation of Pain and they review other tools to assess neuropathic pain. - Prolonged Fever, Hepatosplenomegaly, and Pancytopenia in a 46-Year-Old Woman
Levy L Nasereddin A Rav-Acha M Kedmi M Rund D Gatt ME - PLoS Med 6(4):e1000053 (2009)
- The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors
- PLoS Med 6(4):e1000058 (2009)
Background Knowledge of the number of deaths caused by risk factors is needed for health policy and priority setting. Our aim was to estimate the mortality effects of the following 12 modifiable dietary, lifestyle, and metabolic risk factors in the United States (US) using consistent and comparable methods: high blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure; overweight–obesity; high dietary trans fatty acids and salt; low dietary polyunsaturated fatty acids, omega-3 fatty acids (seafood), and fruits and vegetables; physical inactivity; alcohol use; and tobacco smoking. Methods and Findings We used data on risk factor exposures in the US population from nationally representative health surveys and disease-specific mortality statistics from the National Center for Health Statistics. We obtained the etiological effects of risk factors on disease-specific mortality, by age, from systematic reviews and meta-analyses of epidemiological studies that had adjusted (i) for major potential confounders, and (ii) where possible for regression dilution bias. We estimated the number of disease-specific deaths attributable to all non-optimal levels of each risk factor exposure, by age and sex. In 2005, tobacco smoking and high blood pressure were responsible for an estimated 467,000 (95% confidence interval [CI] 436,000–500,000) and 395,000 (372,000–414,000) deaths, accounting for about one in five or six deaths in US adults. Overweight–obesity (216,000; 188,000–237,000) and physical inactivity (191,000; 164,000–222,000) were each responsible for nearly 1 in 10 death s. High dietary salt (102,000; 97,000–107,000), low dietary omega-3 fatty acids (84,000; 72,000–96,000), and high dietary trans fatty acids (82,000; 63,000–97,000) were the dietary risks with the largest mortality effects. Although 26,000 (23,000–40,000) deaths from ischemic heart disease, ischemic stroke, and diabetes were averted by current alcohol use, they were outweighed by 90,000 (88,000–94,000) deaths from other cardiovascular diseases, cancers, liver cirrhosis, pancreatitis, alcohol use disorders, road traffic and other injuries, and violence. Conclusions Smoking and high blood pressure, which both have effective interventions, are responsible for the largest number of deaths in the US. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of deaths in the US. Please see later in the article for Editors' Summary - Mortality of HIV-Infected Patients Starting Antiretroviral Therapy in Sub-Saharan Africa: Comparison with HIV-Unrelated Mortality
- PLoS Med 6(4):e1000066 (2009)
Background Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV–infected population. We compared mortality rates observed in HIV-1–infected patients starting ART with non-HIV–related background mortality in four countries in sub-Saharan Africa. Methods and Findings Patients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5–21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/µl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55–1.81) per 100 person-years in patients who started with 200 cells/µl or above w ith WHO stage I/II. The corresponding SMRs were 47.1 (39.1–56.6) and 3.44 (1.91–6.17). Among patients who started ART with 200 cells/µl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08–0.94) per 100 person-years and the SMR was 1.14 (0.47–2.77). Conclusions Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART. Please see later in the article for Editors' Summary - Influence of Rapid Malaria Diagnostic Tests on Treatment and Health Outcome in Fever Patients, Zanzibar—A Crossover Validation Study
- PLoS Med 6(4):e1000070 (2009)
Background The use of rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria is being suggested to improve diagnostic efficiency in peripheral health care settings in Africa. Such improved diagnostics are critical to minimize overuse and thereby delay development of resistance to artemisinin-based combination therapies (ACTs). Our objective was to study the influence of RDT-aided malaria diagnosis on drug prescriptions, health outcomes, and costs in primary health care settings. Methods and Findings We conducted a cross-over validation clinical trial in four primary health care units in Zanzibar. Patients of all ages with reported fever in the previous 48 hours were eligible and allocated alternate weeks to RDT-aided malaria diagnosis or symptom-based clinical diagnosis (CD) alone. Follow-up was 14 days. ACT was to be prescribed to patients diagnosed with malaria in both groups. Statistical analyses with multilevel modelling were performed. A total of 1,887 patients were enrolled February through August 2005. RDT was associated with lower prescription rates of antimalarial treatment than CD alone, 361/1005 (36%) compared with 752/882 (85%) (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.03–0.05, p<0.001). Prescriptions of antibiotics were higher after RDT than CD alone, i.e., 372/1005 (37%) and 235/882 (27%) (OR 1.8, 95%CI 1.5–2.2, p<0.001), respectively. Reattendance due to perceived unsuccessful clinical cure was lower after RDT 25/1005 (2.5%), than CD alone 43/882 (4.9%) (OR 0.5, 95% CI 0.3–0.9, p = 0.005). Total average cost per patient was similar: USD 2.47 and 2.37 after RDT and CD alone, respectively. Conclusions RDTs resulted in improved adequate treatment and health outcomes without increased cost per patient. RDTs may represent a tool for improved management of patients with fever in peripheral health care settings. Trial Registration Clinicaltrials.gov NCT00549003 Please see later in the article for Editors' Summary - Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria
Pearce RJ Pota H Evehe MS Bâ el-H Mombo-Ngoma G Malisa AL Ord R Inojosa W Matondo A Diallo DA Mbacham W van den Broek IV Swarthout TD Getachew A Dejene S Grobusch MP Njie F Dunyo S Kweku M Owusu-Agyei S Chandramohan D Bonnet M Guthmann JP Clarke S Barnes KI Streat E Katokele ST Uusiku P Agboghoroma CO Elegba OY Cissé B A-Elbasit IE Giha HA Kachur SP Lynch C Rwakimari JB Chanda P Hawela M Sharp B Naidoo I Roper C - PLoS Med 6(4):e1000055 (2009)
Background Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution. Methods and Findings We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. Resistance lineages were common to all sites within these regions. The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations. Conclusions Resistant dhps has emerged independently in multiple sites in Africa during the past 10–20 years. Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns. - Unrecognized Non-Q-Wave Myocardial Infarction: Prevalence and Prognostic Significance in Patients with Suspected Coronary Disease
Kim HW Klem I Shah DJ Wu E Meyers SN Parker MA Crowley AL Bonow RO Judd RM Kim RJ - PLoS Med 6(4):e1000057 (2009)
Background Unrecognized myocardial infarction (UMI) is known to constitute a substantial portion of potentially lethal coronary heart disease. However, the diagnosis of UMI is based on the appearance of incidental Q-waves on 12-lead electrocardiography. Thus, the syndrome of non-Q-wave UMI has not been investigated. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can identify MI, even when small, subendocardial, or without associated Q-waves. The aim of this study was to investigate the prevalence and prognosis associated with non-Q-wave UMI identified by DE-CMR. Methods and Findings We conducted a prospective study of 185 patients with suspected coronary disease and without history of clinical myocardial infarction who were scheduled for invasive coronary angiography. Q-wave UMI was determined by electrocardiography (Minnesota Code). Non-Q-wave UMI was identified by DE-CMR in the absence of electrocardiographic Q-waves. Patients were followed to determine the prognostic significance of non-Q-wave UMI. The primary endpoint was all-cause mortality. The prevalence of non-Q-wave UMI was 27% (50/185), compared with 8% (15/185) for Q-wave UMI. Patients with non-Q-wave UMI were older, were more likely to have diabetes, and had higher Framingham risk than those without MI, but were similar to those with Q-wave UMI. Infarct size in non-Q-wave UMI was modest (8%±7% of left ventricular mass), and left ventricular ejection fraction (LVEF) by cine-CMR was usually preserved (52%±18%). The prevalence of non-Q-wave UMI increased with the extent and severity of coronar y disease on angiography (p<0.0001 for both). Over 2.2 y (interquartile range 1.8–2.7), 16 deaths occurred: 13 in non-Q-wave UMI patients (26%), one in Q-wave UMI (7%), and two in patients without MI (2%). Multivariable analysis including New York Heart Association class and LVEF demonstrated that non-Q-wave UMI was an independent predictor of all-cause mortality (hazard ratio [HR] 11.4, 95% confidence interval [CI] 2.5–51.1) and cardiac mortality (HR 17.4, 95% CI 2.2–137.4). Conclusions In patients with suspected coronary disease, the prevalence of non-Q-wave UMI is more than 3-fold higher than Q-wave UMI. The presence of non-Q-wave UMI predicts subsequent mortality, and is incremental to LVEF. Trial Registration Clinicaltrials.gov NCT00493168 - Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets
Khurana S Suguitan AL Rivera Y Simmons CP Lanzavecchia A Sallusto F Manischewitz J King LR Subbarao K Golding H - PLoS Med 6(4):e1000049 (2009)
Background Transmission of highly pathogenic avian H5N1 viruses from poultry to humans have raised fears of an impending influenza pandemic. Concerted efforts are underway to prepare effective vaccines and therapies including polyclonal or monoclonal antibodies against H5N1. Current efforts are hampered by the paucity of information on protective immune responses against avian influenza. Characterizing the B cell responses in convalescent individuals could help in the design of future vaccines and therapeutics. Methods and Findings To address this need, we generated whole-genome–fragment phage display libraries (GFPDL) expressing fragments of 15–350 amino acids covering all the proteins of A/Vietnam/1203/2004 (H5N1). These GFPDL were used to analyze neutralizing human monoclonal antibodies and sera of five individuals who had recovered from H5N1 infection. This approach led to the mapping of two broadly neutralizing human monoclonal antibodies with conformation-dependent epitopes. In H5N1 convalescent sera, we have identified several potentially protective H5N1-specific human antibody epitopes in H5 HA[(-10)-223], neuraminidase catalytic site, and M2 ectodomain. In addition, for the first time to our knowledge in humans, we identified strong reactivity against PB1-F2, a putative virulence factor, following H5N1 infection. Importantly, novel epitopes were identified, which were recognized by H5N1-convalescent sera but did not react with sera from control individuals (H5N1 naïve, H1N1 or H3N2 seropos itive). Conclusion This is the first study, to our knowledge, describing the complete antibody repertoire following H5N1 infection. Collectively, these data will contribute to rational vaccine design and new H5N1-specific serodiagnostic surveillance tools. - A Novel Tool for the Assessment of Pain: Validation in Low Back Pain
Scholz J Mannion RJ Hord DE Griffin RS Rawal B Zheng H Scoffings D Phillips A Guo J Laing RJ Abdi S Decosterd I Woolf CJ - PLoS Med 6(4):e1000047 (2009)
Background Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology. Methods and Findings Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with ra dicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%–97%) and specificity (97%; 95% CI 89%–100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs. Conclusions We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.
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