A report of dangerously high carbon monoxide levels within the passenger compartment of a snow-obstructed vehicle

BACKGROUND: We sought to determine how quickly carbon monoxide would accumulate in the passenger compartment of a snow-obstructed vehicle. METHODS: A 1992 sedan was buried in snow to the level of the undercarriage, the ignition was then engaged and carbon monoxide levels recorded at 2.5-minute intervals. The primary outcome was the time at which a lethal carbon monoxide level was detected. Six trials were conducted: windows closed; windows open one inch; windows open 6 inches; windows closed and tailpipe swept clear of snow; windows closed and one cubic foot of snow removed around tailpipe; windows closed and tailpipe completely cleared of snow to ground level in a path 12 inches wide. RESULTS: Lethal levels of carbon monoxide occurred within 2.5 minutes in the vehicle when the windows were closed, within 5 minutes when the widows were opened one inch, and within 7.5 minutes when the widows were opened six inches. Dangerously high levels of carbon monoxide were detected within the vehicle when the tailpipe had been swept clear of snow and when a one cubic foot area had been cleared around the tailpipe. When the tailpipe was completely unobstructed the carbon monoxide level was zero. CONCLUSIONS: Lethal levels of carbon monoxide occurred within minutes in this snow-obstructed vehicle

Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes

Increased renal clearance of thiamine (vitamin B1) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: −76% and −53% respectively, p<0.001; transporter protein −77% and −83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy

Nonergodicity transitions in colloidal suspensions with attractive interactions

The colloidal gel and glass transitions are investigated using the idealized mode coupling theory (MCT) for model systems characterized by short-range attractive interactions. Results are presented for the adhesive hard sphere and hard core attractive Yukawa systems. According to MCT, the former system shows a critical glass transition concentration that increases significantly with introduction of a weak attraction. For the latter attractive Yukawa system, MCT predicts low temperature nonergodic states that extend to the critical and subcritical region. Several features of the MCT nonergodicity transition in this system agree qualitatively with experimental observations on the colloidal gel transition, suggesting that the gel transition is caused by a low temperature extension of the glass transition. The range of the attraction is shown to govern the way the glass transition line traverses the phase diagram relative to the critical point, analogous to findings for the fluid-solid freezing transition.Comment: 11 pages, 7 figures; to be published in Phys. Rev. E (1 May 1999

Informed consent for clinical trials in acute coronary syndromes and stroke following the European Clinical Trials Directive: investigators' experiences and attitudes

<p>Abstract</p> <p>Background</p> <p>During clinical trials in emergency medicine, providing appropriate oral and written information to a patient is usually a challenge. There is little published information regarding patients' opinions and competence to provide informed consent, nor on physicians' attitudes towards the process. We have investigated the problem of obtaining consent from patients in emergency-setting clinical trials (such as acute coronary syndromes (ACS) and stroke) from a physicians' perspective.</p> <p>Methods</p> <p>A standardised anonymous 14-item questionnaire was distributed to Polish cardiac and stroke centres.</p> <p>Results</p> <p>Two hundred and fourteen informative investigator responses were received. Of these investigators, 73.8% had experience with ACS and 25.2% had experience with acute stroke trials (and 1% with both fields). The complete model of informed consent (embracing all aspects required by Good Clinical Practice (GCP) and law) was used in 53.3% of cases in emergency settings, whereas the legal option of proxy consent was not used at all. While less than 15% of respondents considered written information to have been fully read by patients, 80.4% thought that the amount of information being given to emergency patients is too lengthy. Although there is no legal obligation, more than half of the investigators sought parallel consent (assent) from patients' relatives. Most investigators confirmed that they would adopt the model proposed by the GCP guidelines: abbreviated verbal and written consent in emergency conditions with obligatory "all-embracing" deferred consent to continue the trial once the patient is able to provide it. However, this model would not follow current Polish and European legislation.</p> <p>Conclusion</p> <p>An update of national and European regulations is required to enable implementation of the emergency trial consent model referred to in GCP guidelines.</p

Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects

Background: High dose oral thiamine may have a role in treating diabetes, heart failure, and hypermetabolic states. The purpose of this study was to determine the pharmacokinetic profile of oral thiamine hydrochloride at 100 mg, 500 mg and 1500 mg doses in healthy subjects. Methods: This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated. Results: The $AUC_{0-10 hr}$ and $C_{max}$ values increased nonlinearly between 100 mg and 1500 mg. The slope of the $AUC_{0-10 hr}$ vs dose, as well as the $C_{max}$ vs dose, plots are steepest at the lowest thiamine doses. Conclusion: Our study demonstrates that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process

Clinical research without consent in adults in the emergency setting: a review of patient and public views

<p>Abstract</p> <p>Background</p> <p>In emergency research, obtaining informed consent can be problematic. Research to develop and improve treatments for patients admitted to hospital with life-threatening and debilitating conditions is much needed yet the issue of research without consent (RWC) raises concerns about unethical practices and the loss of individual autonomy. Consistent with the policy and practice turn towards greater patient and public involvement in health care decisions, in the US, Canada and EU, guidelines and legislation implemented to protect patients and facilitate acute research with adults who are unable to give consent have been developed with little involvement of the lay public. This paper reviews research examining public opinion regarding RWC for research in emergency situations, and whether the rules and regulations permitting research of this kind are in accordance with the views of those who ultimately may be the most affected.</p> <p>Methods</p> <p>Seven electronic databases were searched: Medline, Embase, CINAHL, Cochrane Database of Systematic Reviews, Philosopher's Index, Age Info, PsychInfo, Sociological Abstracts and Web of Science. Only those articles pertaining to the views of the public in the US, Canada and EU member states were included. Opinion pieces and those not published in English were excluded.</p> <p>Results</p> <p>Considering the wealth of literature on the perspectives of professionals, there was relatively little information about public attitudes. Twelve studies employing a range of research methods were identified. In five of the six questionnaire surveys around half the sample did <it>not </it>agree generally with RWC, though paradoxically, a higher percentage would <it>personally </it>take part in such a study. Unfortunately most of the studies were not designed to investigate individuals' views in any depth. There also appears to be a level of mistrust of medical research and some patients were more likely to accept an experimental treatment 'outside' of a research protocol.</p> <p>Conclusion</p> <p>There are too few data to evaluate whether the rules and regulations permitting RWC protects – or is acceptable to – the public. However, any attempts to engage the public should take place in the context of findings from further basic research to attend to the apparently paradoxical findings of some of the current surveys.</p

Key stakeholder perceptions about consent to participate in acute illness research: a rapid, systematic review to inform epi/pandemic research preparedness

Background A rigorous research response is required to inform clinical and public health decision-making during an epi/pandemic. However, the ethical conduct of such research, which often involves critically ill patients, may be complicated by the diminished capacity to consent and an imperative to initiate trial therapies within short time frames. Alternative approaches to taking prospective informed consent may therefore be used. We aimed to rapidly review evidence on key stakeholder (patients, their proxy decision-makers, clinicians and regulators) views concerning the acceptability of various approaches for obtaining consent relevant to pandemic-related acute illness research. Methods We conducted a rapid evidence review, using the Internet, database and hand-searching for English language empirical publications from 1996 to 2014 on stakeholder opinions of consent models (prospective informed, third-party, deferred, or waived) used in acute illness research. We excluded research on consent to treatment, screening, or other such procedures, non-emergency research and secondary studies. Papers were categorised, and data summarised using narrative synthesis. Results We screened 689 citations, reviewed 104 full-text articles and included 52. Just one paper related specifically to pandemic research. In other emergency research contexts potential research participants, clinicians and research staff found third-party, deferred, and waived consent to be acceptable as a means to feasibly conduct such research. Acceptability to potential participants was motivated by altruism, trust in the medical community, and perceived value in medical research and decreased as the perceived risks associated with participation increased. Discrepancies were observed in the acceptability of the concept and application or experience of alternative consent models. Patients accepted clinicians acting as proxy-decision makers, with preference for two decision makers as invasiveness of interventions increased. Research regulators were more cautious when approving studies conducted with alternative consent models; however, their views were generally under-represented. Conclusions Third-party, deferred, and waived consent models are broadly acceptable to potential participants, clinicians and/or researchers for emergency research. Further consultation with key stakeholders, particularly with regulators, and studies focused specifically on epi/pandemic research, are required. We highlight gaps and recommendations to inform set-up and protocol development for pandemic research and institutional review board processes