Improved understanding of the quality of survival of patients is crucial in evaluating trauma care, understanding recovery patterns and timeframes, and informing healthcare, social, and disability ...service provision. We aimed to describe the longer-term health status of seriously injured patients, identify predictors of outcome, and establish recovery trajectories by population characteristics.
A population-based, prospective cohort study using the Victorian State Trauma Registry (VSTR) was undertaken. We followed up 2,757 adult patients, injured between July 2011 and June 2012, through deaths registry linkage and telephone interview at 6-, 12-, 24-, and 36-months postinjury. The 3-level EuroQol 5 dimensions questionnaire (EQ-5D-3L) was collected, and mixed-effects regression modelling was used to identify predictors of outcome, and recovery trajectories, for the EQ-5D-3L items and summary score. Mean (SD) age of participants was 50.8 (21.6) years, and 72% were male. Twelve percent (n = 333) died during their hospital stay, 8.1% (n = 222) of patients died postdischarge, and 155 (7.0%) were known to have survived to 36-months postinjury but were lost to follow-up at all time points. The prevalence of reporting problems at 36-months postinjury was 37% for mobility, 21% for self-care, 47% for usual activities, 50% for pain/discomfort, and 41% for anxiety/depression. Continued improvement to 36-months postinjury was only present for the usual activities item; the adjusted relative risk (ARR) of reporting problems decreased from 6 to 12 (ARR 0.87, 95% CI: 0.83-0.90), 12 to 24 (ARR 0.94, 95% CI: 0.90-0.98), and 24 to 36 months (ARR 0.95, 95% CI: 0.95-0.99). The risk of reporting problems with pain or discomfort increased from 24- to 36-months postinjury (ARR 1.06, 95% CI: 1.01, 1.12). While loss to follow-up was low, there was responder bias with patients injured in intentional events, younger, and less seriously injured patients less likely to participate; therefore, these patient subgroups were underrepresented in the study findings.
The prevalence of ongoing problems at 3-years postinjury is high, confirming that serious injury is frequently a chronic disorder. These findings have implications for trauma system design. Investment in interventions to reduce the longer-term impact of injuries is needed, and greater investment in primary prevention is needed.
Renal colic is a common, acute presentation of urolithiasis that requires immediate pain relief. European Association of Urology guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) as ...the preferred analgesia. However, the fear of NSAID adverse effects and the uncertainty about superior analgesic effect have maintained the practice of advocating intravenous opioids as the initial analgesia.
The objective of this systematic review and meta-analysis was to compare the safety and efficacy of NSAIDs with opioids and paracetamol (acetaminophen) for the management of acute renal colic.
Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, World Health Organization International Clinical Trials Registry Platform, Google Scholar, and the reference list of retrieved articles were searched up to December 2016 without language restrictions. Two reviewers independently assessed eligible studies using the Cochrane Collaboration tool for assessing and reporting the risk of bias and abstracted data using predefined data fields.
From 468 potentially relevant studies, 36 randomized controlled trials (RCTs) including 4887 patients, published between 1982 and 2016, were included in this systematic review. The treatment effect observed indicated marginal benefit of NSAIDs over opioids in initial pain reduction at 30min (11 RCTs, n=1985, mean difference MD –5.58, 95% confidence interval CI –10.22 to –0.95; heterogeneity I2=81%). In the subgroup analyses by the route of administration, NSAIDs required fewer rescue treatments (seven RCTs, n=541, number needed to treat NNT 11, 95% CI 6–75) and had lower vomiting rates compared with opioids (five RCTs, n=531, NNT 5, 95% CI 4–8). Comparisons of NSAIDs with paracetamol showed no difference for both drugs at 30min (four RCTs, n=1325, MD –5.67, 95% CI –17.52 to 6.18, p=0.35; I2=89%). Patients treated with NSAIDs required fewer rescue treatments (two trials, n=1145, risk ratio 0.56, 95% CI 0.42–0.74, p<0.001; I2=0%).
NSAIDs were equivalent to opioids or paracetamol in the relief of acute renal colic pain at 30min. There was less vomiting and fewer requirements for rescue analgesia with NSAIDs compared with opioids. Patients treated with NSAIDs required less rescue analgesia compared with paracetamol. Despite observed heterogeneity among the included studies and the overall quality of evidence, the findings of a lower need for rescue analgesia and fewer adverse events, in conjunction with the practical advantages of ease of delivery, suggest that NSAIDs should be the preferred analgesic option for patients presenting to the emergency department with renal colic.
In kidney stone–related acute pain episodes in patients with adequate renal function, treatment with nonsteroidal anti-inflammatory drugs offers effective and most sustained pain relief, with fewer side effects, when compared with opioids or paracetamol.
Nonsteroidal anti-inflammatory drugs (NSAIDS) provided effective and most sustained pain relief with fewer side effects. The combined pragmatic benefits of ease of administration and lack of analgesia abuse or addiction properties establish NSAIDS as the first-line analgesia to treat acute renal colic pain.
The introduction of the bacterium Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Evidence of a reduction in dengue case ...incidence following field releases of wMel-infected Ae. aegypti has been reported previously from a cluster randomised controlled trial in Indonesia, and quasi-experimental studies in Indonesia and northern Australia.
Following pilot releases in 2015-2016 and a period of intensive community engagement, deployments of adult wMel-infected Ae. aegypti mosquitoes were conducted in Niterói, Brazil during 2017-2019. Deployments were phased across four release zones, with a total area of 83 km2 and a residential population of approximately 373,000. A quasi-experimental design was used to evaluate the effectiveness of wMel deployments in reducing dengue, chikungunya and Zika incidence. An untreated control zone was pre-defined, which was comparable to the intervention area in historical dengue trends. The wMel intervention effect was estimated by controlled interrupted time series analysis of monthly dengue, chikungunya and Zika case notifications to the public health surveillance system before, during and after releases, from release zones and the control zone. Three years after commencement of releases, wMel introgression into local Ae. aegypti populations was heterogeneous throughout Niterói, reaching a high prevalence (>80%) in the earliest release zone, and more moderate levels (prevalence 40-70%) elsewhere. Despite this spatial heterogeneity in entomological outcomes, the wMel intervention was associated with a 69% reduction in dengue incidence (95% confidence interval 54%, 79%), a 56% reduction in chikungunya incidence (95%CI 16%, 77%) and a 37% reduction in Zika incidence (95%CI 1%, 60%), in the aggregate release area compared with the pre-defined control area. This significant intervention effect on dengue was replicated across all four release zones, and in three of four zones for chikungunya, though not in individual release zones for Zika.
We demonstrate that wMel Wolbachia can be successfully introgressed into Ae. aegypti populations in a large and complex urban setting, and that a significant public health benefit from reduced incidence of Aedes-borne disease accrues even where the prevalence of wMel in local mosquito populations is moderate and spatially heterogeneous. These findings are consistent with the results of randomised and non-randomised field trials in Indonesia and northern Australia, and are supportive of the Wolbachia biocontrol method as a multivalent intervention against dengue, chikungunya and Zika.
Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to ...promote Ag presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14
CD16
), intermediate (CD14
CD16
), and nonclassical (CD14
CD16
) monocytes. Monocytes sorted from nonfrail healthy adults (21-40 y) and old (≥65 y) individuals were analyzed after stimulation with TLR4, TLR7/8, and retinoic acid-inducible gene I agonists. Our data showed that under nonstimulated conditions, monocyte subsets did not reveal significant age-related alternations; however, agonist stimulated-monocytes from adults and old subjects did show differences at the transcriptional and functional levels. These alternations in many immune-related transcripts and biological processes resulted in reduced production of IFN-α, IFN-γ, IL-1β, CCL20, and CCL8, and higher expression of CX3CR1 in monocytes from old subjects. Our findings represent a comprehensive analysis of the influence of human aging on pattern recognition receptors signaling and monocyte functions, and have implications for strategies to enhance the immune response in the context of infection and immunization.
Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department ...with septic shock. However, its effectiveness is uncertain.
In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization.
Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.
In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE ClinicalTrials.gov number, NCT00975793.).
The successful establishment of the wMel strain of Wolbachia for the control of arbovirus transmission by Aedes aegypti has been proposed and is being implemented in a number of countries. Here we ...describe the successful establishment of the wMel strain of Wolbachia in four sites in Yogyakarta, Indonesia. We demonstrate that Wolbachia can be successfully introgressed after transient releases of wMel-infected eggs or adult mosquitoes. We demonstrate that the approach is acceptable to communities and that Wolbachia maintains itself in the mosquito population once deployed. Finally, our data show that spreading rates of Wolbachia in the Indonesian setting are slow which may reflect more limited dispersal of Aedes aegypti than seen in other sites such as Cairns, Australia.
Abstract Background and objectives Acute traumatic coagulopathy (ATC) has been reported in the setting of isolated traumatic brain injury (iTBI) and associated with high mortality and poor outcomes. ...The aim of this systematic review was to examine the incidence and outcome of patients with ATC in the setting of iTBI. Methods We conducted a search of the MEDLINE database and Cochrane library, focused on subject headings and keywords involving coagulopathy and TBI. Design and results of each study were described. Studies were assessed for heterogeneity and the pooled incidence of ATC in the setting of iTBI determined. Reported outcomes were described. Results There were 22 studies selected for analysis. A statistically significant heterogeneity among the studies was observed ( p < 0.01). Using the random effects model the pooled proportion of patients with ATC in the setting of iTBI was 35.2% (95% CI: 29.0–41.4). Mortality of patients with ATC and iTBI ranged between 17% and 86%. Higher blood transfusion rates, longer hospital stays, longer ICU stays, decreased ventilator free days, higher rates of single and multiple organ failure and higher incidence of delayed injury and disability at discharge were reported among patients with ATC. Conclusions ATC is commonly associated with iTBI and almost uniformly associated with worse outcomes. Any disorder of coagulation above the normal range appears to be associated with worse outcomes and therefore a clinically important target for management. Earlier identification of patients with ATC and iTBI, for recruitment into prospective trials, presents avenues for further research.
We report a Monte Carlo algorithm for calculation of occupied (“network”) and unoccupied (“void”) space in crystal structures. The variation of the volumes of the voids and the network of ...intermolecular contacts with pressure sensitively reveals discontinuities associated with first- and second-order phase transitions, providing insights into the effect of compression (and, in principle, other external stimuli) at a level between those observed in individual contact distances and the overall unit cell dimensions. The method is shown to be especially useful for the correlation of high-pressure crystallographic and spectroscopic data, illustrated for naphthalene, where a phase transition previously detected by vibrational spectroscopy, and debated in the literature for over 80 years, has been revealed unambiguously in crystallographic data for the first time. Premonitory behavior before a phase transition and crystal collapse at the end of a compression series has also been detected. The network and void volumes for 129 high-pressure studies taken from the Cambridge Structural Database (CSD) were fitted to equation of state to show that networks typically have bulk moduli between 40 and 150 GPa, while those of voids fall into a much smaller range, 2–5 GPa. These figures are shown to reproduce the narrow range of overall bulk moduli of molecular solids (ca. 5–20 GPa). The program, called CellVol, has been written in Python using the CSD Python API and can be run through the command line or through the Cambridge Crystallographic Data Centre’s Mercury interface.
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