The risk of being culpable for or involved in a road crash after using cannabis: A systematic review and meta-analyses

Background The development of drug driving policies should rest on sound epidemiological evidence as to the crash risks of driving after using psychoactive drugs. The findings from individual studies of the increased risk of crashing from the acute use of cannabis range in size from no increase (and perhaps even a protective effect) to a 10-fold increase. Coherent cannabis-driving policies cannot readily be developed from such an incoherent evidence base. A weighted average measure of risk, as provided by a meta-analysis, might be useful. However, if the range of risks found in the cannabis-crash studies reflects the different ways that a variety of biases are being expressed, then the simple application of a meta-analysis might provide little more than an average measure of bias. In other words, if the biases were predominantly inflationary, the meta-analysis would give an inflated estimate of crash risk; and if the biases were predominantly deflationary, the meta-analysis would give a deflated estimate of risk. Review We undertook a systematic search of electronic databases, and identified 13 culpability studies and 4 case–control studies from which cannabis-crash odds ratios could be extracted. Random-effects meta-analyses gave summary odds ratios of 1.37 (1.10–1.69) for the culpability studies and 1.45 (0.94–2.25) for the case–control studies. A tool was designed to identify and score biases arising from: confounding by uncontrolled covariates; inappropriate selection of cases and controls; and the inappropriate measurement of the exposure and outcome variables. Each study was scrutinised for the presence of those biases, and given a total ‘directional bias score’. Most of the biases were inflationary. A meta-regression against the total directional bias scores was performed for the culpability studies, giving a bias-adjusted summary odds ratio of 0.68 (0.45–1.05). The same analysis could not be performed for the case–control studies because there were only four such studies. Nonetheless, a monotonic relationship was found between the total bias scores and the cannabis-crash odds ratios, with Spearman's rho = 0.95, p = 0.05, indicating that the summary odds ratio of 1.45 is an overestimate. It is evident that the risks from driving after using cannabis are much lower than from other behaviours such as drink-driving, speeding or using mobile phones while driving. With the medical and recreational use of cannabis becoming more prevalent, the removal of cannabis-presence driving offences should be considered (while impairment-based offences would remain).

The Effects of Ascorbic Acid Over Sepsis: Meta-analysis With Trial Sequential Analysis

Background: This meta-analysis is performed to evaluate the effects of AA on the mortality over sepsis patients, focusing on the courses and initiation of treatment as well as AA doses.Methods: Randomized controlled trials concerning sepsis patients treated with intravenous AA were included when searching the database. The meta-analysis was performed using the random (M-H heterogeneity) model to produce summary odds ratio with 95% CI. Trial sequential analysis was applied to evaluated the effect of random errors.Results: The included 12 trials enrolled a total of 1232 patients. Intravenously administration of AA could not lower 28-day mortality over sepsis patients (OR = 0.81; 95% CI (0.54-1.23); p = 0.326). Subgroup analysis demonstrated that when administrating AA alone, in a dose ≥ 10 g/d, or within 6 h of admission, the result may turn to positive (OR = 0.36; 95% CI (0.15-0.86); p = 0.020, OR = 0.50; 95% CI (0.27-0.92); p = 0.025, OR = 0.49; 95% CI (0.27-0.89); p = 0.019, relatively). The quality of evidence is moderate.Conclusion: IV AA may have no effects to lower mortality over sepsis patients. However, when administrating AA alone, in a dose ≥ 10 g/d, or within 6 h of admission, the result may turn to positive. Due to a moderate GRADE certainty of evidence, further studies are required to fully elaborate the effectiveness of AA during the management of the sepsis patients.PROSPERO registration number: CRD 42020170825. 24 Feb, 2020 retrospectively registered.

Prognostic significance of U2AF1 mutations in myelodysplastic syndromes: a meta-analysis

Introduction Although the effects of U2 small nuclear RNA auxiliary factor 1 gene ( U2AF1) mutations on the outcomes of patients with myelodysplastic syndromes (MDS) have previously been investigated, their prognostic significance remains controversial. We performed a meta-analysis to investigate the impact of U2AF1 mutations on MDS progression. Methods Two reviewers independently extracted information such as hazard ratios (HRs) and 95% confidential intervals (CIs) for overall survival (OS) and leukemia-free survival (LFS) as well as the number of surviving patients each year after diagnosis from the included studies. Results Thirteen studies with a total of 3038 patients were included. The summary odds ratio (OR) for U2AF1 mutations with an OS of 5 years was 0.37, the summary HR for U2AF1 mutations in OS was 1.60, and the summary OR for an OS of 5 years in patients with U2AF1S34 and U2AF1Q157 was 3.68. There were no significant differences in leukemia-free survival or hypomethylating therapy response between patients with and without U2AF1 mutations. Conclusion U2AF1 mutations were associated with poor survival in MDS patients, and patients with U2AF1Q157 had a worse OS than those with U2AF1S34. Our findings suggest that MDS patients with U2AF1 mutations could benefit more from hypomethylation therapy.

Association between prodynorphin gene polymorphisms and opioid dependence susceptibility: a meta-analysis

Background Prodynorphin (PDYN) gene polymorphisms have been linked with opioid dependence (OD) with conflicting outcomes, the aim of this study is to synthesize the existing evidence of the association between PDYN polymorphisms and OD susceptibility. Methods Four databases including PubMed, EMBASE, Web of Science, and Wanfang were retrieved for relevant studies before August, 2018. All identified studies were evaluated using predetermined inclusion and exclusion criteria. Summary odds ratio (OR) and 95% confidence interval (95%CI) were calculated to appraise the association. Statistical analysis was performed using RevMan 5.3 software. Results A total of seven case-control studies with 3129 cases and 3289 controls were recruited in the meta-analysis. For rs910080, rs1997794, rs1022563, and rs2235749 polymorphisms of PDYN gene, there were six, four, five, and four studies eventually included, respectively. The findings indicated that rs910080 polymorphism was significantly correlated with OD among Asian population under allelic model (A vs. G, OR = 1.30, 95% CI 1.04–1.62, P = 0.02, FDR = 0.05) and dominant model (AA+AG vs. GG, OR = 1.25, 95% CI 1.04–1.51, P = 0.02, FDR = 0.05). However, rs1022563, rs1997794 and rs2235749 polymorphisms did not appear to associate with OD susceptibility. Conclusions There existed a significant association between rs1022563 polymorphism and OD among Asian population. As the included studies were not adequate to guarantee a robust and convincing conclusion, future studies with larger sample size among more ethnicities are recommended.

Gatifloxacin is superior to levofloxacin and moxifloxacin in shorter treatment regimens for multidrug-resistant TB

SETTING: Data were collected from patients starting one of the shorter treatment regimens (STRs) for multidrug-resistant tuberculosis (MDR-TB) in Bangladesh, Niger or Cameroon.OBJECTIVE: To estimate the effect of either a gatifloxacin (GFX), moxifloxacin (MFX) or levofloxacin (LVX) based STR on bacteriological effectiveness.DESIGN: Retrospective study of prospectively collected data.RESULTS: Among 1530 patients, bacteriological effectiveness was 96.7% overall. Stratified by treatment with a GFX-, LVX- or MFX-based regimen effectiveness was respectively 97.5%, 95.5% and 94.7%. Compared to those on a GFX-based regimen, the estimated summary odds ratio of having an adverse outcome was more than double (OR 2.05, 95% CI 1.09–3.90) in patients treated with either an LVX-based or MFX-based regimen. After adjusting for initial resistance, patients treated with an LVX-based regimen and MFX-based regimen had respectively a 4.5- and 8.4-fold times larger odds of an adverse bacteriological outcome. None among 859 patients at risk treated with a GFX-based compared to at least 4 of 228 among those on an MFX-based regimen acquired fluoroquinolone resistance.CONCLUSION: GFX-based regimens had superior bacteriological effectiveness than MFX-based or LVX-based regimens. As GFX is currently unavailable in most MDR-TB programs, its reintroduction should be prioritised.

Unusually High Incidences of Pseudomonas Bacteremias Within Topical Polymyxin–Based Decolonization Studies of Mechanically Ventilated Patients: Benchmarking the Literature

Background Topical polymyxin (PM)–based regimens to decolonize patients receiving prolonged mechanical ventilation (MV) have been widely studied. However, paradoxical bacteremia incidences remain unexplained. Methods The literature was searched for studies of topical PM–based regimens used to decontaminate MV patients reporting incidences of overall and Pseudomonas bacteremia data. In addition, observational groups without any intervention and trials of various interventions other than topical PM (non-PM studies) served to provide external benchmarks and additional points of reference, respectively. The bacteremia incidences were extracted from the control and intervention (component) groups of these studies and compared with metaregression using generalized estimating equation methods. Results The summary odds ratio derived from studies of topical PM–based interventions against overall bacteremia was 0.60 (95% confidence interval [CI], 0.53–0.69). Benchmark incidences per 100 MV patients for overall (mean, 8.9%; 95% CI, 6.9% to 10.9%) and Pseudomonas (mean, 0.7%; 95% CI, 0.5% to 1.1%) bacteremia were derived from 16 observational studies. By contrast, among 17 studies of topical PM, the mean incidences among control groups for overall (mean, 15.3%; 95% CI, 11.5% to 20.3%) and Pseudomonas (mean, 1.6%; 95% CI, 0.9% to 3.1%) bacteremia were both higher, whereas these incidences in the intervention groups for both topical PM and non-PM studies were in each case more similar to the respective benchmarks. These paradoxical incidences cannot readily be explained in metaregression models. Conclusions Paradoxically, despite an apparent prevention effect of topical PM–based methods against bacteremia overall, the incidences of Pseudomonas bacteremia within the component groups of these studies are unusually high vs literature-derived benchmarks.

Association between serum calcium, serum phosphate and aortic stenosis with implications for prevention

Background Aortic stenosis is the most common cause of valvular heart disease with no means of prevention. Lowering serum levels of calcium or phosphate are potential preventive strategies but observational studies on the associations with aortic stenosis are inconsistent. Design and methods A case–control study was conducted in 132 individuals undergoing echocardiography (63 with aortic stenosis and 69 without) and the results combined with three other comparable studies (914 individuals overall) to provide a summary odds ratio of aortic stenosis for a 0.1 mmol/L increase (approximately one standard deviation) in calcium and phosphate respectively. The relationship between calcium and phosphate and the severity of aortic stenosis, according to peak trans-aortic velocity, was also examined in the case–control study using linear regression. Results Both calcium and phosphate were positively associated with aortic stenosis. The summary odds ratio for a 0.1 mmol/L increase in calcium was 1.79 (95% confidence interval 1.07–2.99), p = 0.027 and for phosphate it was 1.47 (1.08–2.01), p = 0.015. Peak trans-aortic velocity increased with phosphate levels, 9% (4%–14%) per 0.1 mmol/L, p = 0.001, but not with calcium, p = 0.089. Conclusions If the associations are causal and reversible, these results indicate that a small reduction in calcium or phosphate levels, within the physiological rage, would translate into a clinically significant reduction in the risk of aortic stenosis. Randomised trials of calcium and phosphate lowering therapies in aortic stenosis are needed.

Exposure to Nitrogen Oxide in the First Trimester and Risk of Cardiovascular-Related Malformations: A Dose-Response Meta-Analysis of Observational Studies

Nitrogen oxide (NOx) is produced during combustion at high temperature, which is a major constituent of air pollutants. Recent studies suggested inconsistent results on the association between NOx exposure and cardiovascular-related malformations. We aimed to assess aforementioned association in pregnant women in the first trimester and cardiovascular-related malformations of infants. A systematic literature review identified studies for observational studies about NOx exposure and cardiovascular-related malformation in PubMed. Random-effect models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned association. Finally, nine studies met the inclusion criteria. Overall, the SOR of cardiovascular-related malformation per 10 ppb increment in NOx and NO2 concentration was 1.01 (95% CI: 0.98–1.04; I2 = 38.6%, P=0.09) and 0.99 (95% CI: 0.95–1.04; I2 = 37.8%, P=0.13), respectively. Stratifying by study design, geographic locations, and confounded adjustments, the majority of strata showed negative results, which were consistent with the main findings. However, we found that exposure to NOx and NO2 in the first trimester increased the risk of coarctation of the aorta (COA) malformation by 13% and 19%, respectively. Our study provided limited evidence regarding the association between NOx exposure in the first trimester and cardiovascular-related malformations in infants.

OP90 Do Patients With Open Fractures Need Urgent Surgery?

Introduction:Calling in staff and preparing the operating room for an urgent surgical procedure is a significant draw on hospital resources and disrupts care of other patients. It has been common practice to treat open fractures on an urgent basis. HTA methods can be applied to examine this prioritization of care, just like they can be applied to the acquisition of drugs and devices.Methods:Our center completed a rapid systematic review of guidelines, systematic reviews, and primary clinical evidence, on urgent surgical debridement and stabilization of open fractures of long bones (“urgent” being defined as within six hours of the injury) compared to surgical debridement and reduction performed at a later time point. Meta-analyses were performed for infection and non-union outcomes and the GRADE system was used to assess the strength of evidence for each conclusion.Results:We found no published clinical guidelines for the urgency of treating open fractures. A good systematic review on the topic was published in 2012. We found six cohort studies published since completion of the earlier review. The summary odds ratio for any infection in patients with later treatment was 0.97 (95% confidence interval (CI) 0.78–1.22, sixteen studies, 3,615 patients) and for deep or “major” infections was 1.00 (95% CI 0.74–1.34, nine studies, 2,013 patients). The summary odds ratio of non-union with later treatment was 0.95 (95% CI 0.65–1.41, six studies, 1,308 patients). There was no significant heterogeneity in any of the results (I-squared = 0 percent) and no apparent trends in the results as a function of study size or publication date. We graded the strength of each of the conclusions as very low because they were based on cohort studies where the treating physician could elect immediate treatment for patients with severe soft-tissue injuries or patients at risk of complications. This raises the risk of spectrum bias.Conclusions:Default urgent scheduling of patients with open fractures for surgical debridement and stabilization does not appear to reduce the risk of infection or fracture non-union. Based on this information, our surgery department managers no longer schedule patients with open fractures for immediate surgery unless there are specific circumstances necessitating it.