Publications by authors named "Havel C"

Background: Good neurological outcome after cardiac arrest is difficult to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical for a favourable prognosis. Experimental evidence suggests that therapeutic hypothermia is beneficial, and several clinical studies on this topic have been published.

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Tobacco-specific nitrosamines (TSNAs) are emitted during smoking and form indoors by nitrosation of nicotine. Two of them, '-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are human carcinogens with No Significant Risk Levels (NSRLs) of 500 and 14 ng day, respectively. Another TSNA, 4-(methylnitrosamino)-4-(3-pyridyl) butanal (NNA), shows genotoxic and mutagenic activity .

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Aim: Most of the carcinogenic pollutants coming from tobacco smoking or other combustion processes tend to accumulate in settled house dust (SHD) over time. This study evaluated the load of these pollutants in smokers and non-smokers' houses from relatively fresh SHD collected in five different districts on the island of Malta.

Methods: An improved, efficient extraction method to obtain three fractions from a 200 mg of SHD was developed.

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The most important tobacco-specific nitrosamine found in cigarette smoke and formed in ageing smoke after cigarettes are extinguished is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). It is formed from nitrosation of nicotine, under particular conditions both in indoor and outdoor environments. NNK has been classified as a potent lung carcinogen which is expected to be found primarily in the particle-phase and to be stable in particulate matter.

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In studies of tobacco toxicology, including comparisons of different tobacco products and exposure to secondhand or thirdhand smoke, exposure assessment using biomarkers is often useful. Some studies have indicated that most of the toxicity of tobacco smoke is due to gas-phase compounds. 3-Ethenylpyridine (3-EP) is a major nicotine pyrolysis product occurring in the gas phase of tobacco smoke.

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Objective: Early diagnosis or rule-out of acute coronary syndrome (ACS) is a key competence of emergency medicine. Changes in the NSTE-ACS guidelines of the European Society of Cardiology (ESC) in 2015 and 2020 both warranted a henceforth more conservative approach regarding high-sensitivity troponin t (hsTnt) testing. We aimed to assess the impact of more conservative guidelines on the frequency of early rule-out and prolonged observation with repeated hsTnt testing at a high-volume tertiary care emergency department.

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Second Hand Smoke (SHS) has always been primarily linked with indoor pollution. To date nicotine was the favoured marker for SHS alongside measurements of particulate matter (PM) levels. As nicotine is mainly found in the gas-phase and reactive in the outdoor environment it is not ideal as a marker for the SHS-driven particulate component in PM.

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Introduction: Dual use of electronic cigarettes (e-cigarettes) and combustible cigarettes is a major public health issue. It is generally accepted that exclusive e-cigarette use is less harmful than exclusive combustible cigarette use, but most e-cigarette users continue to smoke combustible cigarettes as well. To what extent the use of e-cigarettes reduces harm in people who continue to smoke combustible cigarettes has been debated.

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Introduction: Many electronic cigarette manufacturers have begun offering liquids containing "nicotine salts," which are formed when an acid is mixed in a solution with free-base nicotine. Type of salt could play a significant role in the abuse liability of electronic cigarette liquids. As a first step to understanding nicotine salts, this study sought to identify the types of acids present in 23 commercially available electronic cigarette liquids.

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Aim: To describe systemic nicotine exposure and subjective effects of electronic cigarettes (e-cigarettes) in people who use both e-cigarettes and cigarettes (dual users), including within-subject comparisons of e-cigarette and cigarette use.

Design: Two-arm, counterbalanced cross-over study. Participants used their usual brand of e-cigarette or cigarette during a standardized session in a 2-week study.

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Background: The implementation of computerized monitoring and prescription systems in intensive care has proven to be reliable in reducing the rate of medical error and increasing patient care time. They also showed a benefit in reducing the length of stay in the intensive care unit (ICU). However, this benefit has been poorly studied, with conflicting results.

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1,4-Butanediol (BDO)-used as solvent and abused for its euphoric effects-is converted to gamma-hydroxybutyrate (GHB) by the enzyme alcohol dehydrogenase. This double-blind, placebo-controlled crossover study with six healthy volunteers is the first to date investigating the role of the ADH inhibitor fomepizole (4-methylpyrazole (4MP)) in moderating this conversion in humans. Participants received on two different days either intravenous placebo or 15 mg/kg 4MP followed by oral administration of 25 mg/kg BDO.

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Rationale: Gamma-hydroxybutyrate acid (GHB), a GABA receptor agonist approved for treatment of narcolepsy, impairs driving ability, but little is known about doses and plasma concentrations associated with impairment and time course of recovery.

Objective: To assess effects of oral GHB (Xyrem®) upon driving as measured by a driving simulator, and to determine plasma concentrations associated with impairment and the time course of recovery.

Methods: Randomized, double-blind, two-arm crossover study, during which 16 participants received GHB 50 mg/kg orally or placebo.

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Background: Heated tobacco products (also called 'heat-not-burn' products) heat tobacco at temperatures below that of combustion, causing nicotine and other compounds to aerosolise. One such product, IQOS from Philip Morris International, is being marketed internationally with claims of harm reduction. We sought to determine whether exposure to IQOS aerosol impairs arterial flow-mediated dilation (FMD), a measure of vascular endothelial function that is impaired by tobacco smoke.

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Synthetic cannabinoid receptor agonists (SCRAs) are a dynamic class of new psychoactive substances (NPS), with novel chemotypes emerging each year. Following the putative detection of 5F-CUMYL-P7AICA in Australia in 2016, the scaffold-hopping SCRAs 5F-CUMYL-PICA, 5F-CUMYL-PINACA, and 5F-CUMYL-P7AICA were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-quadrupole time-of-flight-MS (LC-QTOF-MS). Since little is known of the pharmacology of 7-azaindole SCRAs like 5F-CUMYL-P7AICA, the binding affinities and functional activities of all compounds at cannabinoid type 1 and type 2 receptors (CB and CB , respectively) were assessed using tritiated radioligand competition experiments and fluorescence-based plate reader membrane potential assays.

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Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice.

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Objectives: The quality of telephone-assisted cardiopulmonary resuscitation (CPR) needs improvement. This study investigates whether a dispatchers' perception is an adequate measure of the actual quality of CPR provided by laypersons.

Material And Methods: Individual participant data from 3 randomized simulation trials, with identical methodology but different interventions, were combined for this analysis.

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Article Synopsis
  • The study aimed to understand how different e-liquid flavors (strawberry, tobacco, and usual) impact nicotine intake and the pharmacological effects of e-cigarettes.
  • In a controlled trial with 14 participants, results showed that while nicotine inhaled was similar between strawberry and tobacco flavors after initial puffs, plasma nicotine levels were significantly higher with strawberry.
  • The findings indicate that e-liquid flavors affect nicotine exposure and absorption rates, potentially influencing subjective experiences like satisfaction and heart rate changes, with users adjusting their intake depending on the flavor.
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Objective: To characterize vaping behavior and nicotine intake during e-cigarette access.

Methods: Thirteen adult e-cigarette users had 90 minutes of videotaped access to their usual e-cigarette. Plasma nicotine was measured before and every 15 minutes after the first puff; subjective effects were measured before and after the session.

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Thirdhand smoke (THS) is the fraction of cigarette smoke that persists in indoor environments after smoking. We investigated the effects of neonatal and adult THS exposure on bodyweight and blood cell populations in C57BL/6 J mice. At the end of neonatal exposure, THS-treated male and female mice had significantly lower bodyweight than their respective control mice.

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Introduction: Characterization of aerosols generated by electronic cigarettes (e-cigarettes) is one method used to evaluate the safety of e-cigarettes. While some researchers have modified smoking machines for e-cigarette aerosol generation, these machines are either not readily available, not automated for e-cigarette testing or have not been adequately described. The objective of this study was to build an e-cigarette vaping machine that can be used to test, under standard conditions, e-liquid aerosolization and nicotine and toxicant delivery.

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Background: Targeted temperature management (also known under 'therapeutic hypothermia', 'induced hypothermia'", or 'cooling') has been shown to be beneficial for neurological outcome in patients who have had successful resuscitation from sudden cardiac arrest, but it remains unclear when this intervention should be initiated.

Objectives: To assess the effects of pre-hospital initiation of cooling on survival and neurological outcome in comparison to in-hospital initiation of cooling for adults with pre-hospital cardiac arrest.

Search Methods: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, BIOSIS, and three trials registers from inception to 5 March 2015, and carried out reference checking, citation searching, and contact with study authors to identify additional studies.

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Objective: Mortality is frequently used as an outcome in critical care trials, being a patient-orientated variable and robust against information/selection bias. Mortality frequency, however, should be measured at a defined time point of follow-up. Practice of meta-analysis shows that follow-up times of trials in critical care medicine differ substantially.

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Background: Initial goal-directed resuscitation for hypotensive shock usually includes administration of intravenous fluids, followed by initiation of vasopressors. Despite obvious immediate effects of vasopressors on haemodynamics, their effect on patient-relevant outcomes remains controversial. This review was published originally in 2004 and was updated in 2011 and again in 2016.

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