A Systematic Review of the Risks of Motor Vehicle Crashes Associated with Psychiatric Disorders.

OBJECTIVE: Psychiatric disorders and their treatments have the potential to adversely impact driving skills. However, it is unclear to what extent this poses a public health risk by increasing the risk of motor vehicle crashes (MVCs). The aim of this systematic review was to synthesize and critically appraise evidence on the risk of MVC for drivers with psychiatric disorders. METHOD: We conducted a systematic review of the MVC risk associated with psychiatric disorders using seven databases in November 2019. Two reviewers examined each study and extracted data. The National Heart, Lung, and Blood Institute Quality Assessment tools were used to assess each study's quality of evidence. RESULTS: We identified 24 studies that met the inclusion criteria, including eight cohort, 10 case-control, and six cross-sectional designs. Quality assessment ratings were "Good" for four studies, "Fair" for 10, and "Poor" for 10. Self-report or questionnaires were used in place of objective measures of either MVC, psychiatric disorder, or both in 12 studies, and only seven adjusted for driving exposure. Fifteen studies reported an increased risk of MVC associated with psychiatric disorders, and nine did not. There was no category of disorder that was consistently associated with increased MVC risk. CONCLUSION: The available evidence is mixed, not of high quality, and does not support a blanket restriction on drivers with psychiatric disorder. An individualized approach, as recommended by international guidelines, should continue. Further research should include objective assessments of psychiatric disorders and MVC risk and adjust for driving exposure.

Risk of Motor Vehicle Collision or Driving Impairment After Traumatic Brain Injury: A Collaborative International Systematic Review and Meta-Analysis.

OBJECTIVE: To synthesize knowledge of the risk of motor vehicle collision (MVC) following a traumatic brain injury (TBI) and the associated risk of driving impairment, as measured by on-road tests, computerized simulators, and self-reported or state-recorded driving records. METHODS: Our international team searched 7 databases for studies published between 1990 and 2015 of people with TBI, controls, and data concerning either MVC or driving impairment. The included articles examined the risk of MVC among people with TBI; we excluded studies that examined the risk of having a TBI associated with being involved in an MVC. RESULTS: From 13 578 search results, we included 8 studies involving 1663 participants with TBI and 4796 controls. We found no significant difference in the risk of MVC (odds ratio = 1.24, 95% confidence interval = 0.80-1.91, P = .34). When we restricted the analysis to self-report, the risk of MVC was higher for those without a TBI (odds ratio = 1.63, 95% confidence interval = 1.21-2.22, P = .002). In contrast, participants with TBI consistently performed worse during on-road assessments and had more problems with vehicular control. CONCLUSION: Limitations of reviewed studies included small sample sizes, failure to specify TBI severity or time postinjury, and absence of objective measures of risk. Findings concerning the relationship between TBIs from non-MVC causes and crash risk are, therefore, inconclusive and do not provide evidence for major changes to existing clinical guidelines for driving with TBI.

WITHDRAWN: Angioplasty (versus non surgical management) for intermittent claudication.

BACKGROUND: Intermittent claudication is pain in the legs due to muscle ischaemia associated with arterial stenosis or occlusion. Angioplasty is a technique that involves dilatation and recanalisation of a stenosed or occluded artery. OBJECTIVES: The objective of this review was to determine the effects of angioplasty of arteries in the leg when compared with non surgical therapy, or no therapy, for people with mild to moderate intermittent claudication. SEARCH METHODS: Sources searched include the Cochrane Peripheral Vascular Diseases Group's Specialized Trials Register (August 2006), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2006) and reference lists of relevant articles. The review authors also contacted investigators in the field and handsearched relevant conference proceedings (August 2006). SELECTION CRITERIA: Randomised trials of angioplasty for mild or moderate intermittent claudication. DATA COLLECTION AND ANALYSIS: The contact author selected suitable trials and this was checked by the other review author. Both review authors assessed trial quality independently. The contact author extracted data and this was cross checked by the other review author. MAIN RESULTS: Two trials with a total of 98 participants were included. The average age was 62 years old with 20 women and 78 men. Participants were followed for two years in one trial and six years in the other.At six months follow up, mean ankle brachial pressure indices were higher in the angioplasty groups than control groups (mean difference 0.17; 95% confidence interval (CI) 0.11 to 0.24). In one trial, walking distances were greater in the angioplasty group, but in the other trial, in which controls underwent an exercise programme, walking distances did not show a greater improvement in the angioplasty group. At two years follow up in one trial, the angioplasty group were more likely to have a patent artery (odds ratio 5.5; 95% CI 1.8 to 17.0) but not a significantly better walking distance or quality of life. In the other trial, long term follow up at six years demonstrated no significant differences in outcome between the angioplasty and control groups. AUTHORS' CONCLUSIONS: These limited results suggest that angioplasty may have had a short term benefit, but this may not have been sustained.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: An intention-to-treat analysis of amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon angioplasty-first revascularization strategy.

BACKGROUND: A 2005 interim analysis of the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed that in patients with severe lower limb ischemia (SLI; rest pain, ulceration, gangrene) due to infrainguinal disease, bypass surgery (BSX)-first and balloon angioplasty (BAP)-first revascularization strategies led to similar short-term clinical outcomes, although BSX was about one-third more expensive and morbidity was higher. We have monitored patients for a further 2.5 years and now report a final intention-to-treat (ITT) analysis of amputation-free survival (AFS) and overall survival (OS). METHODS: Of 452 enrolled patients in 27 United Kingdom hospitals, 228 were randomized to a BSX-first and 224 to a BAP-first revascularization strategy. All patients were monitored for 3 years and more than half for >5 years. RESULTS: At the end of follow-up, 250 patients were dead (56%), 168 (38%) were alive without amputation, and 30 (7%) were alive with amputation. Four were lost to follow-up. AFS and OS did not differ between randomized treatments during the follow-up. For those patients surviving 2 years from randomization, however, BSX-first revascularization was associated with a reduced hazard ratio (HR) for subsequent AFS of 0.85 (95% confidence interval [CI], 0.5-1.07; P = .108) and for subsequent OS of 0.61 (95% CI, 0.50-0.75; P = .009) in an adjusted, time-dependent Cox proportional hazards model. For those patients who survived for 2 years after randomization, initial randomization to a BSX-first revascularization strategy was associated with an increase in subsequent restricted mean overall survival of 7.3 months (95% CI, 1.2-13.4 months, P = .02) and an increase in restricted mean AFS of 5.9 months (95% CI, 0.2-12.0 months, P = .06) during the subsequent mean follow-up of 3.1 years (range, 1-5.7 years). CONCLUSIONS: Overall, there was no significant difference in AFS or OS between the two strategies. However, for those patients who survived for at least 2 years after randomization, a BSX-first revascularization strategy was associated with a significant increase in subsequent OS and a trend towards improved AFS.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: Health-related quality of life outcomes, resource utilization, and cost-effectiveness analysis.

BACKGROUND: The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed that survival in patients with severe lower limb ischemia (rest pain, tissue loss) who survived postintervention for >2 years after initial randomization to bypass surgery (BSX) vs balloon angioplasty (BAP) was associated with an improvement in subsequent amputation-free and overall survival of about 6 and 7 months, respectively. We now compare the effect on hospital costs and health-related quality of life (HRQOL) of the BSX-first and BAP-first revascularization strategies using a within-trial cost-effectiveness analysis. METHODS: We measured HRQOL using the Vascular Quality of Life Questionnaire (VascuQol), the Short Form 36 (SF-36), and the EuroQol (EQ-5D) health outcome measure up to 3 years from randomization. Hospital use was measured and valued using United Kingdom National Health Service hospital costs over 3 years. Analysis was by intention-to-treat. Incremental cost-effectiveness ratios were estimated for cost per quality-adjusted life-year (QALY) gained. Uncertainty was assessed using nonparametric bootstrapping of incremental costs and incremental effects. RESULTS: No significant differences in HRQOL emerged when the two treatment strategies were compared. During the first year from randomization, the mean cost of inpatient hospital treatment in patients allocated to BSX ($34,378) was estimated to be about $8469 (95% confidence interval, $2,417-$14,522) greater than that of patients allocated to BAP ($25,909). Owing to increased costs subsequently incurred by the BAP patients, this difference decreased at the end of follow-up to $5521 ($45,322 for BSX vs $39,801 for BAP) and was no longer significant. The incremental cost-effectiveness ratio of a BSX-first strategy was $184,492 per QALY gained. The probability that BSX was more cost-effective than BAP was relatively low given the similar distributions in HRQOL, survival, and hospital costs. CONCLUSIONS: Adopting a BSX-first strategy for patients with severe limb ischemia does result in a modest increase in hospital costs, with a small positive but insignificant gain in disease-specific and generic HRQOL. However, the real-world choice between BSX-first and BAP-first revascularization strategies for severe limb ischemia due to infrainguinal disease cannot depend on costs alone and will require a more comprehensive consideration of individual patient preferences conditioned by expectations of survival and other health outcomes.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: Analysis of amputation free and overall survival by treatment received.

BACKGROUND: An intention-to-treat analysis of randomized Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial data showed that initial randomization to a bypass surgery (BSX)-first strategy was associated with improvements in subsequent overall survival (OS) and amputation-free survival (AFS) of about 7 and 6 months, respectively. We describe the nature and timing of first, crossover, and reinterventions and examine AFS and OS by first treatment received. We also compare vein with prosthetic BSX and transluminal with subintimal balloon angioplasty (BAP) and examine outcomes from BSX after failed BAP. METHODS: We randomly assigned 452 patients with SLI due to infrainguinal disease in 27 United Kingdom hospitals to a BSX first (n = 228) or a BAP first (n = 224) revascularization strategy. All patients have been monitored for 3 years and more than half for >5 years. We prospectively collected data on every procedure, major amputation, and death. RESULTS: Patients randomized to BAP were more likely to have their assigned treatment first (94% vs 85%, P = .01, chi(2)test). BAP had a higher immediate technical failure rate of 20% vs 2.6% (P = .01, chi(2)test). By 12 weeks after randomization 9 BAP (4%) vs 23 BSX (10%) patients had not undergone revascularization; 3 BAP (1.3%) vs 13 BSX (5.8%) had undergone the opposite treatment first; and 35 BAP (15.6%) and 2 (0.9%) BSX had received the assigned treatment and then undergone the opposite treatment. BSX distal anastomoses were divided approximately equally between the above and below knee popliteal and crural arteries; most originated from the common femoral artery. About 25% of the grafts were prosthetic and >90% of vein BSX used ipsilateral great saphenous vein. Most (80%) BAP patients underwent treatment of the SFA alone (38%) or combined with the popliteal artery (42%) and crural arteries (20%). Outcome of vein BSX was better for AFS (P = 0.003) but not OS (P = 0.38, log-rank tests) than prosthetic BSX. There were no differences in outcome between approximately equal numbers of transluminal and subintimal BAP. AFS (P = 0.006) but not OS (P = 0.06, log rank test) survival was significantly worse after BSX after failed BAP than after BSX as a first revascularization attempt. CONCLUSIONS: BAP was associated with a significantly higher early failure rate than BSX. Most BAP patients ultimately required surgery. BSX outcomes after failed BAP are significantly worse than for BSX performed as a first revascularization attempt. BSX with vein offers the best long term AFS and OS and, overall, BAP appears superior to prosthetic BSX.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: A description of the severity and extent of disease using the Bollinger angiogram scoring method and the TransAtlantic Inter-Society Consensus II classification.

BACKGROUND: The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed in patients with severe lower limb ischemia (rest pain, tissue loss) who survive for 2 years after intervention that initial randomization to bypass surgery, compared with balloon angioplasty, was associated with an improvement in subsequent amputation-free survival and overall survival of about 6 and 7 months, respectively. The aim of this report is to describe the angiographic severity and extent of infrainguinal arterial disease in the BASIL trial cohort so that the trial outcomes can be appropriately generalized to other patient cohorts with similar anatomic (angiographic) patterns of disease. METHODS: Preintervention angiograms were scored using the Bollinger method and the TransAtlantic Inter-Society Consensus (TASC) II classification system by three consultant interventional radiologists and two consultant vascular surgeons unaware of the treatment received or patient outcomes. RESULTS: As was to be expected from the randomization process, patients in the two trial arms were well matched in terms of angiographic severity and extent of disease as documented by Bollinger and TASC II. In patients with the least overall disease, it tended to be concentrated in the superficial femoral and popliteal arteries, which were the commonest sites of disease overall. The below knee arteries became increasingly involved as the overall severity of disease increased, but the disease in the above knee arteries did not tend to worsen. The posterior tibial artery was the most diseased crural artery, whereas the peroneal appeared relatively spared. There was less interobserver disagreement with the Bollinger method than with the TASC II classification system, which also appears inherently less sensitive to clinically important differences in infrapopliteal disease among patients with severe leg ischemia. CONCLUSIONS: Anatomic (angiographic) disease description in patients with severe leg ischemia requires a reproducible scoring system that is sensitive to differences in crural artery disease. The Bollinger system appears well suited for this purpose, but the TASC II classification system less so. We hope this detailed analysis will facilitate appropriate generalization of the BASIL trial data to other groups of patients affected by similar anatomic (angiographic) patterns of disease.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: A survival prediction model to facilitate clinical decision making.

BACKGROUND: An intention-to-treat analysis of the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed that in patients with severe lower limb ischemia (SLI) due to infrainguinal disease who survived for 2 years after intervention, initial randomization to a bypass surgery (BSX)-first vs balloon angioplasty (BAP)-first revascularization strategy was associated with improvements in subsequent overall survival (OS) and amputation-free survival (AFS) of about 7 and 6 months, respectively. This study explored the value of baseline factors to estimate the likelihood of survival to 2 years for the trial cohort (Cox model) and for individual BASIL trial patients (Weibull model) as an aid to clinical decision making. METHODS: Of 452 patients presenting to 27 United Kingdom hospitals, 228 were randomly assigned to a BSX-first and 224 to a BAP-first revascularization strategy. Patients were monitored for at least 3 years. Baseline factors affecting the survival of the entire cohort were examined with a multivariate Cox model. The chances of survival at 1 and 2 years for patients with given baseline characteristics were estimated with a Weibull parametric model. RESULTS: At the end of follow-up, 172 patients (38%) were alive without major limb amputation of the trial leg, and 202 (45%) were alive. Baseline factors that were significant in the Cox model were BASIL randomization stratification group, below knee Bollinger angiogram score, body mass index, age, diabetes, creatinine level, and smoking status. Using these factors to define five equally sized groups, we identified patients with 2-year survival rates of 50% to 90%. The factors that contributed to the Weibull predictive model were age, presence of tissue loss, serum creatinine, number of ankle pressure measurements detectable, maximum ankle pressure measured, a history of myocardial infarction or angina, a history of stroke or transient ischemia attack, below knee Bollinger angiogram score, body mass index, and smoking status. CONCLUSIONS: Patients in the BASIL trial were at high risk of amputation and death regardless of revascularization strategy. However, baseline factors can be used to stratify those risks. Furthermore, within a parametric Weibull model, certain of these factors can be used to help predict outcomes for individuals. It may thus be possible to define the clinical and anatomic (angiographic) characteristics of SLI patients who are likely-and not likely-to live for >2 years after intervention. Used appropriately in the context of the BASIL trial outcomes, this may aid clinical decision making regarding a BSX- or BAP-first revascularization strategy in SLI patients like those randomized in BASIL.

Changes in scanning laser polarimetry before and after laser capsulotomy for posterior capsular opacification.

PURPOSE: To investigate changes in scanning laser polarimetry with variable corneal compensation (GDx-VCC) parameters caused by posterior capsular opacification (PCO). METHODS: In this comparative case-control series, 20 eyes due to undergo YAG laser capsulotomy for PCO were recruited. GDx-VCC was performed before and after laser capsulotomy, and digital photographs were taken of the PCO to assess their severity and type. The other eye of each subject was used as the control group. RESULTS: Typical scan score was significantly improved after laser from 33 to 55.1 (P=0.001; n=19) and TSNIT score was significantly lower, dropping from 62.3 to 58.9 (P=0.03; n=19). There was no change in the nerve fiber index. All parameters in the control group remained unchanged except the Q-score which rose from 8.1 to 8.8 (P=0.05; n=16). There was no correlation between severity of PCO or the pearly/fibrous nature and the change in parameter values. CONCLUSIONS: We conclude that in subjects being considered with GDx-VCC, the presence of visually significant PCO may introduce artifact as judged by the typical scan score.

Development and characterization of a scalable controlled precipitation process to enhance the dissolution of poorly water-soluble drugs.

PURPOSE: Poorly water-soluble compounds are being found with increasing frequency among pharmacologically active new chemical entities, which is a major concern to the pharmaceutical industry. Some particle engineering technologies have been shown to enhance the dissolution of many promising new compounds that perform poorly in formulation and clinical studies (Rogers et. al., Drug Dev Ind Pharm 27:1003-1015). One novel technology, controlled precipitation, shows significant potential for enhancing the dissolution of poorly soluble compounds. In this study, controlled precipitation is introduced; and process variables, such as mixing zone temperature, are investigated. Finally, scale-up of controlled precipitation from milligram or gram to kilogram quantities is demonstrated. METHODS: Dissolution enhancement capabilities were established using two poorly water-soluble model drugs, danazol and naproxen. Stabilized drug particles from controlled precipitation were compared to milled, physical blend, and bulk drug controls using particle size analysis (Coulter), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), dissolution testing (USP Apparatus 2), and residual solvent analysis. RESULTS: Stabilized nano- and microparticles were produced from controlled precipitation. XRD and SEM analyses confirmed that the drug particles were crystalline. Furthermore, the stabilized particles from controlled precipitation exhibited significantly enhanced dissolution properties. Residual solvent levels were below FDA limits. CONCLUSIONS: Controlled precipitation is a viable and scalable technology that can be used to enhance the dissolution of poorly water-soluble pharmaceutical compounds.

Bypass versus angioplasty to treat severe limb ischemia: factors that affect treatment preferences of UK surgeons and interventional radiologists.

OBJECTIVE: There is continuing controversy as to whether surgical bypass or angioplasty should be first-line treatment of severe limb ischemia. We undertook this study to examine angiographic and clinical factors that influence the treatment of severe limb ischemia by vascular surgeons and interventional radiologists. METHODS: Twenty consultant vascular surgeons and 17 consultant vascular interventional radiologists evaluated 596 hypothetical clinical or angiographic scenarios, and recorded whether, in their opinion, the most appropriate first-line treatment was surgical bypass, angioplasty, or primary amputation. Stepwise multiple linear regression was used to identify the factors that significantly affected responses from the entire group and from surgeons and radiologists separately. RESULTS: There were significant differences between surgeons and radiologists with regard to how clinical and angiographic variables determined treatment preferences. Increasing disease severity, absence of runoff into the foot, presence of a suitable vein, and tissue loss as opposed to rest pain only (the latter only significant to surgeons) all increased the response score toward surgery. However, surgeons and radiologists weighted each of these factors quite differently. Even in the most complex statistical model, 19% of surgical and 13% of radiologic response variations remained unexplained. CONCLUSIONS: Individual surgeons and radiologists vary considerably in their views of the relative merits of surgery and angioplasty in patients with severe limb ischemia. This broad gray area mandates the need for randomized controlled trial data to inform joint decision-making and to optimize patient outcome.

Multidetector computed tomography imaging of aortoenteric fistula.

Three case reports illustrating multidetector computed tomography (CT) imaging findings of secondary aortoenteric fistula (AEF) are described and presented in axial sections, multiplanar reformats, and 3-dimensional reconstruction. Fistulae occurred in the early and late postgrafting period and involved both end-to-end and end-to-side aortic graft anastomoses. Multidetector CT is quick and accurate in the diagnosis of bleeding AEF.