To estimate the global burden of nontyphoidal Salmonella gastroenteritis, we synthesized existing data from laboratory-based surveillance and special studies, with a hierarchical preference to (1) ...prospective population-based studies, (2) dquo;multiplier studies, dquo; (3) disease notifications, (4) returning traveler data, and (5) extrapolation. We applied incidence estimates to population projections for the 21 Global Burden of Disease regions to calculate regional numbers of cases, which were summed to provide a global number of cases. Uncertainty calculations were performed using Monte Carlo simulation. We estimated that 93.8 million cases (5th to 95th percentile, 61.8–131.6 million) of gastroenteritis due to Salmonella species occur globally each year, with 155,000 deaths (5th to 95th percentile, 39,000–303,000 deaths). Of these, we estimated 80.3 million cases were foodborne. Salmonella infection represents a considerable burden in both developing and developed countries. Efforts to reduce transmission of salmonellae by food and other routes must be implemented on a global scale.
Over the past two decades the number of opioid pain relievers sold in the United States rose dramatically. This rise in sales was accompanied by an increase in opioid-related overdose deaths. In ...response, forty-nine states (all but Missouri) created prescription drug monitoring programs to detect high-risk prescribing and patient behaviors. Our objectives were to determine whether the implementation or particular characteristics of the programs were effective in reducing opioid-related overdose deaths. In adjusted analyses we found that a state's implementation of a program was associated with an average reduction of 1.12 opioid-related overdose deaths per 100,000 population in the year after implementation. Additionally, states whose programs had robust characteristics-including monitoring greater numbers of drugs with abuse potential and updating their data at least weekly-had greater reductions in deaths, compared to states whose programs did not have these characteristics. We estimate that if Missouri adopted a prescription drug monitoring program and other states enhanced their programs with robust features, there would be more than 600 fewer overdose deaths nationwide in 2016, preventing approximately two deaths each day.
Objective To estimate the frequency with which results of large randomized clinical trials registered with ClinicalTrials.gov are not available to the public.Design Cross sectional analysisSetting ...Trials with at least 500 participants that were prospectively registered with ClinicalTrials.gov and completed prior to January 2009.Data sources PubMed, Google Scholar, and Embase were searched to identify published manuscripts containing trial results. The final literature search occurred in November 2012. Registry entries for unpublished trials were reviewed to determine whether results for these studies were available in the ClinicalTrials.gov results database.Main outcome measures The frequency of non-publication of trial results and, among unpublished studies, the frequency with which results are unavailable in the ClinicalTrials.gov database.Results Of 585 registered trials, 171 (29%) remained unpublished. These 171 unpublished trials had an estimated total enrollment of 299 763 study participants. The median time between study completion and the final literature search was 60 months for unpublished trials. Non-publication was more common among trials that received industry funding (150/468, 32%) than those that did not (21/117, 18%), P=0.003. Of the 171 unpublished trials, 133 (78%) had no results available in ClinicalTrials.gov.Conclusions Among this group of large clinical trials, non-publication of results was common and the availability of results in the ClinicalTrials.gov database was limited. A substantial number of study participants were exposed to the risks of trial participation without the societal benefits that accompany the dissemination of trial results.
Endothelial cells transduce mechanical forces from blood flow into intracellular signals required for vascular homeostasis. Here we show that endothelial NOTCH1 is responsive to shear stress, and is ...necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation, phenotypes induced by laminar shear stress. NOTCH1 receptor localizes downstream of flow and canonical NOTCH signaling scales with the magnitude of fluid shear stress. Reduction of NOTCH1 destabilizes cellular junctions and triggers endothelial proliferation. NOTCH1 suppression results in changes in expression of genes involved in the regulation of intracellular calcium and proliferation, and preventing the increase of calcium signaling rescues the cell-cell junctional defects. Furthermore, loss of Notch1 in adult endothelium increases hypercholesterolemia-induced atherosclerosis in the descending aorta. We propose that NOTCH1 is atheroprotective and acts as a mechanosensor in adult arteries, where it integrates responses to laminar shear stress and regulates junctional integrity through modulation of calcium signaling.
OBJECTIVE:To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype.
...BACKGROUND:Hyperfibrinolysis is a central component of acute traumatic coagulopathy but a group of patients present with low levels of VHA-detected fibrinolysis. There is concern that these patients may be at risk of thrombosis if empirically administered an antifibrinolytic agent.
METHODS:A prospective multicenter observational cohort study was conducted at 5 European major trauma centers. Blood was drawn on arrival, within 2 hours of injury, for VHA (rotation thromboelastometry ROTEM) and fibrinolysis plasma protein analysis including the fibrinolytic mediator S100A10. An outcomes-based threshold for ROTEM hypofibrinolysis was determined and patients grouped by this and by D-dimer (DD) levels.
RESULTS:Nine hundred fourteen patients were included in the study. The VHA maximum lysis (ML) lower threshold was determined to be <5%. Heterogeneity existed among patients with low ML, with survivors sharing similar clinical and injury characteristics to patients with normal ML values (5–15%). Those who died were critically injured with a preponderance of traumatic brain injury and had a 7-fold higher DD level (died vs. survived103,170 vs. 13,672 ng/mL, P < 0.001). Patients with low ML and high DD demonstrated a hyperfibrinolytic biomarker profile, low tissue plasminogen activator levels but high plasma levels of S100A10. S100A10 was negatively correlated with %ML (r = −0.26, P < 0.001) and caused a significant reduction in %ML when added to whole blood ex-vivo.
CONCLUSIONS:Patients presenting with low ML and low DD levels have low injury severity and normal outcomes. Conversely, patients with low ML but high DD levels are severely injured, functionally coagulopathic and have poor clinical outcomes. These patients have low tissue plasminogen activator levels and are not detectable by ROTEM. S100A10 is a cell surface plasminogen receptor which may drive the hyperfibrinolysis in these patients and which when shed artificially lowers %ML ex-vivo.
IMPORTANCE From January 1, 2003, through December 31, 2010, drug overdose deaths in Tennessee increased from 422 to 1059 per year. More of these deaths involved prescription opioids than heroin and ...cocaine combined. OBJECTIVE To assess the contribution of certain opioid-prescribing patterns to the risk of overdose death. DESIGN, SETTING, AND PARTICIPANTS We performed a matched case-control study that analyzed opioid prescription data from the Tennessee Controlled Substances Monitoring Program (TNCSMP) from January 1, 2007, through December 31, 2011, to identify risk factors associated with opioid-related overdose deaths from January 1, 2009, through December 31, 2010. Case patients were ascertained from death certificate data. Age- and sex-matched controls were randomly selected from among live patients in the TNCSMP. MAIN OUTCOMES AND MEASURES We defined a high-risk number of prescribers or pharmacies as 4 or more per year and high-risk dosage as a daily mean of more than 100 morphine milligram equivalents (MMEs) per year. The main outcome was opioid-related overdose death. RESULTS From January 1, 2007, through December 31, 2011, one-third of the population of Tennessee filled an opioid prescription each year, and opioid prescription rates increased from 108.3 to 142.5 per 100 population per year. Among all patients in Tennessee prescribed opioids during 2011, 7.6% used more than 4 prescribers, 2.5% used more than 4 pharmacies, and 2.8% had a mean daily dosage greater than 100 MMEs. Increased risk of opioid-related overdose death was associated with 4 or more prescribers (adjusted odds ratio aOR, 6.5; 95% CI, 5.1-8.5), 4 or more pharmacies (aOR, 6.0; 95% CI, 4.4-8.3), and more than 100 MMEs (aOR, 11.2; 95% CI, 8.3-15.1). Persons with 1 or more risk factor accounted for 55% of all overdose deaths. CONCLUSIONS AND RELEVANCE High-risk use of prescription opioids is frequent and increasing in Tennessee and is associated with increased overdose mortality. Use of prescription drug–monitoring program data to direct risk-reduction measures to the types of patients overrepresented among overdose deaths might reduce mortality associated with opioid abuse.
Background. Most human infections are caused by closely related serotypes within 1 species of Salmonella. Few data are available on differences in severity of disease among common serotypes. Methods. ...We examined data from all cases of Salmonella infection in FoodNet states during 1996–2006. Data included serotype, specimen source, hospitalization, and outcome. Results. Among 46,639 cases, 687 serotypes were identified. Overall, 41,624 isolates (89%) were from stool specimens, 2524 (5%) were from blood, and 1669 (4%) were from urine; 10,393 (22%) cases required hospitalization, and death occurred in 219 (0.5%). The case fatality rate for S. Newport (0.3%) was significantly lower than for Typhimurium (0.6%); Dublin (3.0%) was higher. With respect to invasive disease, 13 serotypes had a significantly higher proportion than Typhimurium (6%), including Enteritidis (7%), Heidelberg (13%), Choleraesuis (57%), and Dublin (64%); 13 serotypes were significantly less likely to be invasive. Twelve serotypes, including Enteritidis (21%) and Javiana (21%), were less likely to cause hospitalization than Typhimurium (24%); Choleraesuis (60%) was significantly more so. Conclusions. Salmonella serotypes are closely related genetically yet differ significantly in their pathogenic potentials. Understanding the mechanisms responsible for this may be key to a more general understanding of the invasiveness of intestinal bacterial infections.
We report an outbreak of severe acute respiratory syndrome coronavirus 2 involving 3 Malayan tigers (Panthera tigris jacksoni) at a zoo in Tennessee, USA. Investigation identified naturally occurring ...tiger-to-tiger transmission; genetic sequence change occurred with viral passage. We provide epidemiologic, environmental, and genomic sequencing data for animal and human infections.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. Hemolytic uremic syndrome (HUS) is a life-threatening illness usually caused by infection with Shiga toxin-producing Escherichia coli O157 (STEC O157). We evaluated the age-specific rate ...of HUS and death among persons with STEC O157 infection and the risk factors associated with developing HUS. Methods. STEC O157 infections and HUS cases were reported from 8 sites participating in the Foodborne Diseases Active Surveillance Network during 2000–2006. For each case of STEC O157 infection and HUS, demographic and clinical outcomes were reported. The proportion of STEC O157 infections resulting in HUS was determined. Results. A total of 3464 STEC O157 infections were ascertained; 218 persons (6.3%) developed HUS. The highest proportion of HUS cases (15.3%) occurred among children aged <5 years. Death occurred in 0.6% of all patients with STEC O157 infection and in 4.6% of those with HUS. With or without HUS, persons aged ⩾60 years had the highest rate of death due to STEC O157 infection. Twelve (3.1%) of 390 persons aged ⩾60 years died, including 5 (33.3%) of 15 persons with HUS and 7 (1.9%) of 375 without. Among children aged <5 years, death occurred in 4 (3.0%) of those with HUS and 2 (0.3%) of those without. Conclusions. Young children and females had an increased risk of HUS after STEC O157 infection. With or without HUS, elderly persons had the highest proportion of deaths associated with STEC O157 infection. These data support recommendations for aggressive supportive care of young children and the elderly early during illness due to STEC O157.
Clinical trial registries can improve the validity of trial results by facilitating comparisons between prospectively planned and reported outcomes. Previous reports on the frequency of planned and ...reported outcome inconsistencies have reported widely discrepant results. It is unknown whether these discrepancies are due to differences between the included trials, or to methodological differences between studies. We aimed to systematically review the prevalence and nature of discrepancies between registered and published outcomes among clinical trials.
We searched MEDLINE via PubMed, EMBASE, and CINAHL, and checked references of included publications to identify studies that compared trial outcomes as documented in a publicly accessible clinical trials registry with published trial outcomes. Two authors independently selected eligible studies and performed data extraction. We present summary data rather than pooled analyses owing to methodological heterogeneity among the included studies.
Twenty-seven studies were eligible for inclusion. The overall risk of bias among included studies was moderate to high. These studies assessed outcome agreement for a median of 65 individual trials (interquartile range IQR 25-110). The median proportion of trials with an identified discrepancy between the registered and published primary outcome was 31%; substantial variability in the prevalence of these primary outcome discrepancies was observed among the included studies (range 0% (0/66) to 100% (1/1), IQR 17-45%). We found less variability within the subset of studies that assessed the agreement between prospectively registered outcomes and published outcomes, among which the median observed discrepancy rate was 41% (range 30% (13/43) to 100% (1/1), IQR 33-48%). The nature of observed primary outcome discrepancies also varied substantially between included studies. Among the studies providing detailed descriptions of these outcome discrepancies, a median of 13 % of trials introduced a new, unregistered outcome in the published manuscript (IQR 5-16%).
Discrepancies between registered and published outcomes of clinical trials are common regardless of funding mechanism or the journals in which they are published. Consistent reporting of prospectively defined outcomes and consistent utilization of registry data during the peer review process may improve the validity of clinical trial publications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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