Search

We characterise, in pointed regular categories, the ideals as the zero-classes of surjective relations. Moreover, we study a variation of the Smith is Huq condition: two surjective left split relations commute as soon as their zero-classes commute. [ABSTRACT FROM AUTHOR]

Background: Internationally, urine on-site testing has been used for detecting drivers under the influence of drugs (DUID) but more and more countries, such as Belgium, are switching to oral fluid screening. Objective: To compare the previous (published in 1999) and current (published 2009) enforcement procedures of DUID in Belgium. The two evaluated procedures differ in the way the drivers are screened by the police (signs of impairment versus signs of recent drug use), the matrix for screening (urine versus oral fluid) and the analytical cut-off concentrations in plasma. Methods: Data on positive screening and confirmation results were gathered from 1st April 2008 to 30th September 2010, when urine screening (Dipro Druglab panels test) was performed; and from 1st October 2010 to 31st March 2013, when an on-site oral fluid test (Securetec Drugwipe 5+) was used. Results: Approximately 4100 data sets related to urine screening and 3900 data sets related to oral fluid screening were studied. Eighty-eight percent of positive urine on-site tests yielded positive results in plasma for cannabis, 21% for cocaine, 20% for amphetamines and 7% for opiates. Sixty-six percent of the positive oral fluid on-site tests yielded positive results in plasma for cannabis, 30% for cocaine, 28% for amphetamines and 8% for opiates. For cannabis, opiates and amphetamines more negative results in plasma were observed in the period of urine screening. Conclusions: The percentage of plasma samples of tested drivers, in which none of the positive screened target drugs were present in a concentration above the legal cut-off value, has decreased from 17% to 8% since the introduction of the current legislation involving oral fluid screening. [ABSTRACT FROM AUTHOR]

Abstract Background Mechanical ventilation (MV) is imperative in many forms of acute respiratory failure (ARF) in COPD patients. Previous studies have shown the difficulty to identify parameters predicting the outcome of COPD patients treated by invasive MV. Our hypothesis was that a non specialized score as the activities daily living (ADL) score may help to predict the outcome of these patients. Methods We studied the outcome of 25 COPD patients admitted to the intensive care unit for ARF requiring invasive MV. The patients were divided into those weaning success (group A n = 17, 68%) or failure (group B n = 8, 32%). We investigated the correlation between the ADL score and the outcome and mortality. Results The ADL score was higher in group A (5.1 ±1.1 vs 3.7 ± 0.7 in group B, p Conclusion Our pilot study demonstrates that the ADL score is predictive of weaning success and mortality at 6 months, suggesting that the assessment of daily activities should be an important component of ARF management in COPD patients.

Background: Informed consent for medical interventions is ethically and legally required; an important aspect of quality and safety in healthcare; and essential to person-centred care. During labour and birth, respecting consent requirements, including respecting refusal, can contribute to a higher sense of choice and control for labouring women. This study examines (1) to what extent and for which procedures during labour and birth women report that consent requirements were not met and/or inadequate information was provided, (2) how frequently women consider consent requirements not being met upsetting and (3) which personal characteristics are associated with the latter., Methods: A national cross-sectional survey was conducted in the Netherlands among women who gave birth up to 5 years previously. Respondents were recruited through social media with the help of influencers and organisations. The survey focused on 10 common procedures during labour and birth, investigating for each procedure if respondents were offered the procedure, if they consented or refused, if the information provision was sufficient and if they underwent unconsented procedures, whether they found this upsetting., Results: 13 359 women started the survey and 11 418 met the inclusion and exclusion criteria. Consent not asked was most often reported by respondents who underwent postpartum oxytocin (47.5%) and episiotomy (41.7%). Refusal was most often over-ruled when performing augmentation of labour (2.2%) and episiotomy (1.9%). Information provision was reported inadequate more often when consent requirements were not met compared with when they were met. Multiparous women had decreased odds of reporting unmet consent requirements compared with primiparous (adjusted ORs 0.54-0.85). There was considerable variation across procedures in how frequently not meeting consent requirements was considered upsetting., Conclusions: Consent for performing a procedure is frequently absent in Dutch maternity care. In some instances, procedures were performed in spite of the woman's refusal. More awareness is needed on meeting necessary consent requirements in order to achieve person-centred and high-quality care during labour and birth., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Very little data is available about the involvement of lifeboat crews in medical emergencies at sea. The aim of this study is to analyze the medical operations at sea performed by the Royal Netherlands Sea Rescue Institution (KNRM)., Methods: This is a retrospective descriptive analysis of all medical operations at sea performed by the KNRM between January 2017 and January 2020. The operations were divided in three groups: with ambulance crew aboard the lifeboat, ambulance crew on land waiting for the arrival of the lifeboat, and autonomous operations (without ambulance crew involvement). The main outcome measures were circumstances, encountered medical problems, follow-up and crew departure time., Results: The KNRM performed 282 medical operations, involving 361 persons. Operations with ambulance crew aboard the lifeboat (n = 39; 42 persons) consisted mainly of persons with serious trauma or injuries; 32 persons (76.2%) were transported to a hospital. Operations with ambulance crew on land (n = 153; 188 persons) mainly consisted of situations where time was essential, such as persons who were still in the water, with risk of drowning (n = 45, 23.9%), on-going resuscitations (n = 9, 4.8%) or suicide attempts (n = 7, 3.7%). 101 persons (53,7%) were transported to a hospital. All persons involved in the autonomous operations (n = 90; 131 persons) had minor injuries. 38 persons (29%) needed additional medical care, mainly for (suspected) fractures or stitches. In 115 (40.8%) of all operations lifeboat crews did not know that there was a medical problem at the time of departure. Crew departure time in operations with ambulance crew aboard the lifeboat (13.7 min, min. 0, max. 25, SD 5.74 min.) was significantly longer than in operations with ambulance crew on land (7.7 min, min. 0, max 21, SD 4.82 min., p < 0.001)., Conclusion: This study provides new information about the large variety of medical emergencies at sea and the way that lifeboat and ambulance crews are involved. Crew departure time in operations with ambulance crew aboard the lifeboat was significantly longer than in operations with ambulance crew on land. This study may provide useful indications for improvement of future medical operations at sea, such as triage, because in 40.8% of operations, it was not known at the time of departure that there was a medical problem., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Concern for symptom exacerbation and treatment drop-out is an important barrier to the implementation of trauma-focused therapy (TFT), especially in people with a psychotic disorder. This study, which was part of a multicenter randomized controlled trial, investigated posttraumatic stress disorder (PTSD) symptom exacerbation during eye movement desensitization reprocessing (EMDR) therapy and prolonged exposure (PE) in a sample of 99 participants with PTSD and psychosis. Symptom exacerbations during the first four sessions (early exacerbation) and between-session exacerbations over the course of therapy were monitored using the PTSD Symptom Scale-Self Report. Analyses of covariance and chi-square tests were conducted to investigate exacerbation rates and their associations with treatment response and drop-out. Both early exacerbation and between-session exacerbation were relatively common (32.3% and 46.5%, respectively) but were unrelated to poor treatment response or an increased likelihood of treatment drop-out. Both clinicians and patients need to be aware that symptom exacerbation during TFT is common and not related to poor outcomes. Symptom exacerbation can be part of the therapeutic process, should be acknowledged and guided, and should not be a barrier to the implementation of TFT in people with psychosis., (© 2023 The Authors. Journal of Traumatic Stress published by Wiley Periodicals LLC on behalf of International Society for Traumatic Stress Studies.)

This study discusses the European Union's proposal for a Regulation on Markets in Crypto-Assets, now subject to formal approval by the European Parliament. The objective is to explore whether it will positively impact the adoption of crypto-assets in the financial sector. The use of crypto-assets is growing. However, some stakeholders in the financial service sector remain skeptical and hesitant to adopt assets that are yet to be defined and have an unclear legal status. This regulatory uncertainty has been identified as the primary reason for the reluctant adoption. The proposed regulation (part of the EU's Digital Finance Strategy) aims to provide this legal certainty for currently unregulated crypto-assets. This study investigates whether or not the proposed regulation can be expected to have the intended effect by reviewing the proposed regulation itself, the opinions and reactions of the various stakeholders, and secondary literature. Findings reveal that such regulation will most likely not accelerate the adoption of crypto-assets in the EU financial services sector, at least not sufficiently or as intended. Some suggestions are made to improve the proposal., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2023.)

Introduction: Many people with psychotic disorders experience symptoms of post-traumatic stress disorder (PTSD). In recent years, several trauma-focused therapies (TFTs), including cognitive restructuring (CR), prolonged exposure (PE), and eye movement desensitization and reprocessing (EMDR) have been studied and found to be safe and effective in reducing PTSD symptoms in individuals with psychosis. However, studies were conducted in different countries, with varying inclusion criteria, therapy duration, control groups, and trial outcomes. RE.PROCESS will be the first study to compare the impact of CR, PE, and EMDR with a waiting list control condition within the same context., Methods and Analysis: This is the protocol of a pragmatic, single-blind, multicentre, superiority randomized controlled trial, in which CR, PE, and EMDR are compared to a waiting list control condition for TFT (WL) in a naturalistic treatment setting. Inclusion criteria are as follows: age ≥ 16 years; meeting full DSM-5 diagnostic criteria for PTSD on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), with a total CAPS score ≥ 23; and a psychotic disorder in the schizophrenia spectrum confirmed by the Structured Clinical Interview for DSM-5 (SCID-5). Participants (N=200) will be randomly allocated to 16 sessions of one of the TFTs or WL, in addition to receiving treatment as usual (TAU) for psychosis. The primary objective is to compare the effects of CR, PE, and EMDR to WL on researcher-rated severity of PTSD symptoms over time from baseline to 6-month follow-up. Secondary objectives are to examine these effects at the separate time-points (i.e., mid-treatment, post-treatment, and at 6-month follow-up) and to test the effects for clinician-rated presence of PTSD diagnosis, and self-rated severity of (complex) PTSD symptoms., Discussion: This is the first RCT to directly compare the effects of CR, PE, and EMDR within the same context to TAU on PTSD symptoms in individuals with psychosis and PTSD. Secondary effects on clinical and functional outcomes will be investigated both directly after therapy and long term., Trial Registration: ISRCTN ISRCTN56150327 . Registered 18 June 2019., (© 2022. The Author(s).)

Background: In patients with septic shock, the impact of the mean arterial pressure (MAP) target on the course of mottling remains uncertain. In this post hoc analysis of the SEPSISPAM trial, we investigated whether a low-MAP (65 to 70 mmHg) or a high-MAP target (80 to 85 mmHg) would affect the course of mottling and arterial lactate in patients with septic shock., Methods: The presence of mottling was assessed every 2 h from 2 h after inclusion to catecholamine weaning. We compared mottling and lactate time course between the two MAP target groups. We evaluated the patient's outcome according to the presence or absence of mottling., Results: We included 747 patients, 374 were assigned to the low-MAP group and 373 to the high-MAP group. There was no difference in mottling and lactate evolution during the first 24 h between the two MAP groups. After adjustment for MAP and confounding factors, the presence of mottling ≥ 6 h during the first 24 h was associated with a significantly higher risk of death at day 28 and 90. Patients without mottling or with mottling < 6 h and lactate ≥ 2 mmol/L have a higher probability of survival than those with mottling ≥ 6 h and lactate < 2 mmol/L., Conclusion: Compared with low MAP target, higher MAP target did not alter mottling and lactate course. Mottling lasting for more than 6 h was associated with higher mortality. Compared to arterial lactate, mottling duration appears to be a better marker of mortality., (© 2022. The Author(s).)

Background: Women experience disrespect and abuse during labour and birth all over the world. While the gravity of many forms of disrespect and abuse is evident, some of its more subtle forms may not always be experienced as upsetting by women. This study examines (1) how often women experience disrespect and abuse during labour and birth in the Netherlands and (2) how frequently they consider such experiences upsetting. We also examine (3) which respondent characteristics (age, ethnicity, educational level and parity) are associated with those experiences of disrespect and abuse that are upsetting, and (4) the associations between upsetting experiences of disrespect and abuse, and women's labour and birth experiences., Methods: Women who gave birth up to five years ago were recruited through social media platforms to participate in an online survey. The survey consisted of 37 questions about experiences of disrespect and abuse divided into seven categories, dichotomised in (1) not experienced, or experienced but not considered upsetting (2) experienced and considered upsetting. A multivariable logistic regression analysis was performed to examine associated characteristics with upsetting experiences of disrespect and abuse. A Chi-square test was used to investigate the association between upsetting experiences of disrespect and abuse and overall birth experience., Results: 13,359 respondents started the questionnaire, of whom 12,239 met the inclusion and exclusion criteria. Disrespect and abuse in terms of 'lack of choices' (39.8%) was reported most, followed by 'lack of communication' (29.9%), 'lack of support' (21.3%) and 'harsh or rough treatment/physical violence' (21.1%). Large variation was found in how frequently certain types of disrespect and abuse were considered upsetting, with 36.3% of women experiencing at least one situation of disrespect and abuse as upsetting. Primiparity and a migrant background were risk factors for experiencing upsetting disrespect and abuse in all categories. Experiencing more categories of upsetting disrespect and abuse was found to be associated with a more negative birth experience., Conclusions: Disrespectful and abusive experiences during labour and birth are reported regularly in the Netherlands, and are often (but not always) experienced as upsetting. This emphasizes an urgent need to implement respectful maternity care, even in high income countries., (© 2022. The Author(s).)

Importance: Resuscitation is a niche example of how the COVID-19 pandemic has affected society in the long term. Those trained in cardiopulmonary resuscitation (CPR) face the dilemma that attempting to save a life may result in their own harm. This is most of all a problem for drowning, where hypoxia is the cause of cardiac arrest and ventilation is the essential first step in reversing the situation., Objective: To develop recommendations for water rescue organizations in providing their rescuers with safe drowning resuscitation procedures during the COVID-19 pandemic., Evidence Review: Two consecutive modified Delphi procedures involving 56 participants from 17 countries with expertise in drowning prevention research, resuscitation, and programming were performed from March 28, 2020, to March 29, 2021. In parallel, PubMed and Google Scholar were searched to identify new emerging evidence relevant to each core element, acknowledge previous studies relevant in the new context, and identify knowledge gaps., Findings: Seven core elements, each with their own specific recommendations, were identified in the initial consensus procedure and were grouped into 4 categories: (1) prevention and mitigation of the risks of becoming infected, (2) resuscitation of drowned persons during the COVID-19 pandemic, (3) organizational responsibilities, and (4) organizations unable to meet the recommended guidelines. The common measures of infection risk mitigation, personal protective equipment, and vaccination are the base of the recommendations. Measures to increase drowning prevention efforts reduce the root cause of the dilemma. Additional infection risk mitigation measures include screening all people entering aquatic facilities, defining criteria for futile resuscitation, and avoiding contact with drowned persons by rescuers with a high-risk profile. Ventilation techniques must balance required skill level, oxygen delivery, infection risk, and costs of equipment and training. Bag-mask ventilation with a high-efficiency particulate air filter by 2 trained rescuers is advised. Major implications for the methods, facilities, and environment of CPR training have been identified, including nonpractical skills to avoid being infected or to infect others. Most of all, the organization is responsible for informing their members about the impact of the COVID-19 pandemic and taking measures that maximize rescuer safety. Research is urgently needed to better understand, develop, and implement strategies to reduce infection transmission during drowning resuscitation., Conclusions and Relevance: This consensus document provides an overview of recommendations for water rescue organizations to improve the safety of their rescuers during the COVID-19 pandemic and balances the competing interests between a potentially lifesaving intervention and risk to the rescuer. The consensus-based recommendations can also serve as an example for other volunteer organizations and altruistic laypeople who may provide resuscitation.

Background: Alterations in the anatomic and biomechanical properties of the ascending aorta (AAo) can give rise to various vascular pathologies. The aim of the current study is to gain additional insights in the biology of the AAo size and function., Methods: We developed an AI based analysis pipeline for the segmentation of the AAo, and the extraction of AAO parameters. We then performed genome-wide association studies of AAo maximum area, AAo minimum area and AAo distensibility in up to 37,910 individuals from the UK Biobank. Variants that were significantly associated with AAo phenotypes were used as instrumental variables in Mendelian randomization analyses to investigate potential causal relationships with coronary artery disease, myocardial infarction, stroke and aneurysms., Findings: Genome-wide association studies revealed a total of 107 SNPs in 78 loci. We annotated 101 candidate genes involved in various biological processes, including connective tissue development (THSD4 and COL6A3). Mendelian randomization analyses showed a causal association with aneurysm development, but not with other vascular diseases., Interpretation: We identified 78 loci that provide insights into mechanisms underlying AAo size and function in the general population and provide genetic evidence for their role in aortic aneurysm development., Competing Interests: Declaration of interests Niek Verweij was employed by Regeneron Pharmaceuticals. Jan Walter Benjamins, Ming Wai Yeung, Yordi J. van de Vegte, M. Abdullah Said, Thijs van der Linden, Daan Ties, Luis E. Juarez-Orozco and Pim van der Harst declare that they have no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Intensive care unit professionals have experience in critical care and its proportionality, collegial decision-making, withholding or withdrawal of treatment deemed futile, and communication with patients' relatives. These elements rely on ethical values from which we must not deviate in a pandemic situation. The recommendations made by the Ethics Commission of the French Intensive Care Society reflect an approach of responsibility and solidarity towards our citizens regarding the potential impact of a pandemic on critical care resources in France, with the fundamental requirement of respect for human dignity and equal access to health care for all.

Objectives: Individualizing a target mean arterial pressure is challenging during the initial resuscitation of patients with septic shock. The Sepsis and Mean Arterial Pressure (SEPSISPAM) trial suggested that targeting high mean arterial pressure might reduce the occurrence of acute kidney injury among those included patients with a past history of chronic hypertension. We investigated whether the class of antihypertensive medications used before the ICU stay in chronic hypertensive patients was associated with the severity of acute kidney injury occurring after inclusion, according to mean arterial pressure target., Design: Post hoc analysis of the SEPSISPAM trial., Setting: The primary outcome was the occurrence of severe acute kidney injury during the ICU stay defined as kidney disease improving global outcome stage 2 or higher. Secondary outcomes were mortality at day 28 and mortality at day 90., Patients: All patients with chronic hypertension included in SEPSISPAM with available antihypertensive medications data in the hospitalization report were included., Measurements and Main Results: We analyzed 297 patients. Severe acute kidney injury occurred in 184 patients, without difference according to pre-ICU exposure to antihypertensive medications. Patients with pre-ICU exposure to angiotensin II receptor blockers had significantly less severe acute kidney injury in the high mean arterial pressure target group (adjusted odd ratio 0.24 with 95% CI [0.09-0.66]; p = 0.006). No statistically significant association was found after adjustment for pre-ICU exposure to antihypertensive medications and survival., Conclusions: Our results suggest that patients with septic shock and chronic hypertension treated with angiotensin II receptor blocker may benefit from a high mean arterial pressure target to reduce the risk of acute kidney injury occurrence., Competing Interests: Dr. Dequin’s institution received funding from Angers University Hospital, the French Ministry of Health, Abionic, Atox Bio, Sphingotec GMBH, Adrenomed, Medspace, Aridis, Merck, Combioxin, GSK, Med-Immune, Genentech INH, Rev-Immune, Faron, Kenta, and Tigenix, and he received support for article research from the French Ministry of Health. Dr. Gonzalez disclosed work for hire. Dr. Teboul received funding from Getinge/Pulsion. Dr. Radermacher’s institution received funding from Deutsche Forschungsgemeinschaft and the German Ministry of Defense. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Disrespect and abuse during labour and birth are increasingly reported all over the world. In 2016, a Dutch client organization initiated an online campaign, #genoeggezwegen (#breakthesilence) which encouraged women to share negative and traumatic maternity care experiences. This study aimed (1) to determine what types of disrespect and abuse were described in #genoeggezwegen and (2) to gain a more detailed understanding of these experiences., Methods: A qualitative social media content analysis was carried out in two phases. (1) A deductive coding procedure was carried out to identify types of disrespect and abuse, using Bohren et al.'s existing typology of mistreatment during childbirth. (2) A separate, inductive coding procedure was performed to gain further understanding of the data., Results: 438 #genoeggezwegen stories were included. Based on the typology of mistreatment during childbirth, it was found that situations of ineffective communication, loss of autonomy and lack of informed consent and confidentiality were most often described. The inductive analysis revealed five major themes: ''lack of informed consent"; ''not being taken seriously and not being listened to"; ''lack of compassion"; ''use of force"; and ''short and long term consequences". "Left powerless" was identified as an overarching theme that occurred throughout all five main themes., Conclusion: This study gives insight into the negative and traumatic maternity care experiences of Dutch women participating in the #genoeggezwegen campaign. This may indicate that disrespect and abuse during labour and birth do happen in the Netherlands, although the current study gives no insight into prevalence. The findings of this study may increase awareness amongst maternity care providers and the community of the existence of disrespect and abuse in Dutch maternity care, and encourage joint effort on improving care both individually and systemically/institutionally., Competing Interests: We declare that the organizations Hechte Band and Geboortebeweging did not provide funding to carry out this study. Two authors (TL and RV) affiliated with these organizations were part of the research team representing the client. TL is a member of Geboortebeweging, a clinical psychologist and a PhD student (GGzE & Vrije Universiteit). RV is also a member of Geboortebeweging and is a certified babywearing consultant and bonding coach (Hechte Band). Both authors were involved in managing the #GG campaign in 2016, in which they also participated themselves. TL and RV were involved in the research process from the start. They provided feedback on the research proposal and design of the study and contributed to discussing the findings within the research team and writing the paper, all from a client point of view. They were not involved in data collection or analysing the data. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Background: Little is known regarding circumstances, outcomes and quality of cardiopulmonary resuscitation (CPR) and the use of automated external defibrillators (AEDs) performed by operational lifeboat crews. Our aim is to evaluate circumstances, outcomes and quality of CPR performed by the Royal Dutch Lifeboat Institution (KNRM) in out-of-hospital cardiac arrest (OHCA)., Methods: The internal KNRM database has been used to identify and analyse all OHCA cases between July 2011 and December 2017. A limited set of AED data was available to study the quality of CPR., Results: In 37 patients the lifeboat crew members have performed CPR, of which 29 (78.4%) occurred under hostile conditions. The median response time to arrive at the location was 15min. In 11 (29.7%) patients return of spontaneous circulation was achieved at any moment during CPR and 3 (8.1%) patients were still alive after one month. The lifeboat AED was used in 12 patients. Their recordings show a high median compression frequency (120, IQR 111-131) and prolonged median interruption periods (pre-analysis pause 11s (IQR 10-13), post-analysis pause 4s (IQR 3-8), pre-shock pause 24s (IQR 19-26), post-shock pause 6s (IQR 6-11), ventilation pause 6s (IQR 4-8) and other pauses 9s (IQR 4-17))., Conclusions: Compared to most out-of-hospital resuscitations, resuscitations by lifeboat crews have a low incidence, occur under difficult circumstances and in a younger population. AED's on lifeboats have not contributed to any of the survivals. Analysis of AED information can be used to study the quality of CPR and provide input for improving future training of lifeboat crews., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: It is unknown whether the recommended mean arterial pressure (MAP) target of 65 mmHg during initial resuscitation of septic shock is sufficient to maintain cerebral perfusion. Thus, we tested the hypothesis that a higher MAP target in patients with septic shock may improve level of arousal., Methods: We performed a post hoc exploratory analysis of the SEPSISPAM trial, which assessed the effect of a "high-target" level of MAP (80-85 mmHg) versus the recommended "low-target" MAP (65-70 mm Hg) on mortality in patients with septic shock. Among the 776 patients originally recruited in SEPSISPAM trial, we selected those who were mechanically ventilated and sedated and with available evaluation of arousal level assessed by the Richmond Agitation and Sedation Scale (RASS)., Results: We restricted our analysis to the period in which patients were treated with vasoactive drugs. Cumulative sedative drugs were assessed daily. A total of 532 patients were included in this study: 253 (47.6%) in the low-target group and 279 (52.4%) in the high-target group. Daily cumulative sedative drugs were similar in both groups. Compared to the low-target group, minimal and maximal RASS were significantly higher in the high-target group at day 2, 4 and 5. Furthermore, in order to consider the fact that multiple measures were done for each patient and to consider the global effect of time on these measures, we used a mixed linear regression and multivariate models: we confirmed that maximal RASS values were significantly higher in the high-target group., Conclusion: In patients with septic shock who were mechanically ventilated and sedated, resuscitation with MAP target between 80 and 85 mmHg was associated with higher arousal level as compared to a MAP target between 65 and 70 mmHg.

Background: Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial., Methods: In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days., Results: The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients)., Conclusions: Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590 .).

The EFSA Panel on Plant Protection Products and their Residues reviewed the guidance on how aged sorption studies for pesticides should be conducted, analysed and used in regulatory assessment. The inclusion of aged sorption is a higher tier in the groundwater leaching assessment. The Panel based its review on a test with three substances taken from a data set provided by the European Crop Protection Association. Particular points of attention were the quality of the data provided, the proposed fitting procedure of aged sorption experiments and the proposed method for combining results obtained from aged sorption studies and lower-tier studies on degradation and adsorption. Aged sorption was a relevant process in all cases studied. The test revealed that the guidance could generally be well applied and resulted in robust and plausible results. The Panel considers the guidance suitable for use in the groundwater leaching assessment after the recommendations in this Scientific Opinion have been implemented, with the exception of the use of field data to derive aged sorption parameters. The Panel noted that the draft guidance could only be used by experienced users because there is no software tool that fully supports the work flow in the guidance document. It is therefore recommended that a user-friendly software tool be developed. Aged sorption lowered the predicted concentration in groundwater. However, because aged sorption experiments may be conducted in different soils than lower-tier degradation and adsorption experiments, it cannot be guaranteed that the higher tier predicts lower concentrations than the lower tier, while lower tiers should be more conservative than higher tiers. To mitigate this problem, the Panel recommends using all available higher- and lower-tier data in the leaching assessment. The Panel further recommends that aged sorption parameters for metabolites be derived only from metabolite-dosed studies. The formation fraction can be derived from parent-dosed degradation studies, provided that the parent and metabolite are fitted with the best-fit model, which is the double first-order in parallel model in the case of aged sorption., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Background: There is insufficient research into the use of mechanical ventilation with increased inspiratory oxygen concentration (FiO 2 ) and fluid resuscitation with hypertonic saline solution in patients with septic shock. We tested whether these interventions are associated with reduced mortality., Methods: This two-by-two factorial, multicentre, randomised, clinical trial (HYPERS2S) recruited patients aged 18 years and older with septic shock who were on mechanical ventilation from 22 centres in France. Patients were randomly assigned 1:1:1:1 to four groups by a computer generated randomisation list stratified by site and presence or absence of acute respiratory distress syndrome by use of permuted blocks of random sizes. Patients received, in an open-labelled manner, mechanical ventilation either with FiO 2 at 1·0 (hyperoxia) or FiO 2 set to target an arterial haemoglobin oxygen saturation of 88-95% (normoxia) during the first 24 h; patients also received, in a double-blind manner, either 280 mL boluses of 3·0% (hypertonic) saline or 0·9% (isotonic) saline for fluid resuscitation during the first 72 h. The primary endpoint was mortality at day 28 after randomisation in the intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT01722422., Findings: Between Nov 3, 2012, and June 13, 2014, 442 patients were recruited and assigned to a treatment group (normoxia [n=223] or hyperoxia [n=219]; isotonic [n=224] or hypertonic [n=218]). The trial was stopped prematurely for safety reasons. 28 day mortality was recorded for 434 patients; 93 (43%) of 217 patients had died in the hyperoxia group versus 77 (35%) of 217 patients in the normoxia group (hazard ratio [HR] 1·27, 95% CI 0·94-1·72; p=0·12). 89 (42%) of 214 patients had died in the hypertonic group versus 81 (37%) of 220 patients in the isotonic group (HR 1·19, 0·88-1·61; p=0·25). We found a significant difference in the overall incidence of serious adverse events between the hyperoxia (185 [85%]) and normoxia groups (165 [76%]; p=0·02), with a clinically relevant doubling in the hyperoxia group of the number of patients with intensive care unit-acquired weakness (24 [11%] vs 13 [6%]; p=0·06) and atelectasis (26 [12%] vs 13 [6%]; p=0·04) compared with the normoxia group. We found no statistical difference for serious adverse events between the two saline groups (p=0·23)., Interpretation: In patients with septic shock, setting FiO 2 to 1·0 to induce arterial hyperoxia might increase the risk of mortality. Hypertonic (3%) saline did not improve survival., Funding: The French Ministry of Health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Pesticides are regulated in Europe and this process includes an environmental risk assessment (ERA) for non-target arthropods (NTA). Traditionally a non-spatial or field trial assessment is used. In this study we exemplify the introduction of a spatial context to the ERA as well as suggest a way in which the results of complex models, necessary for proper inclusion of spatial aspects in the ERA, can be presented and evaluated easily using abundance and occupancy ratios (AOR). We used an agent-based simulation system and an existing model for a widespread carabid beetle (Bembidion lampros), to evaluate the impact of a fictitious highly-toxic pesticide on population density and the distribution of beetles in time and space. Landscape structure and field margin management were evaluated by comparing scenario-based ERAs for the beetle. Source-sink dynamics led to an off-crop impact even when no pesticide was present off-crop. In addition, the impacts increased with multi-year application of the pesticide whereas current ERA considers only maximally one year. These results further indicated a complex interaction between landscape structure and pesticide effect in time, both in-crop and off-crop, indicating the need for NTA ERA to be conducted at landscape- and multi-season temporal-scales. Use of AOR indices to compare ERA outputs facilitated easy comparison of scenarios, allowing simultaneous evaluation of impacts and planning of mitigation measures. The landscape and population ERA approach also demonstrates that there is a potential to change from regulation of a pesticide in isolation, towards the consideration of pesticide management at landscape scales and provision of biodiversity benefits via inclusion and testing of mitigation measures in authorisation procedures., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The aim of the present study was to assess whether population effects and recovery times increase when a population of a vulnerable aquatic invertebrate is exposed to concentrations of 1 or multiple pesticides. The 2 sets of pesticide combinations tested are typical for orchard and tuber crops in The Netherlands. Exposure concentrations were predicted using the FOCUS step 3 modeling framework and the Dutch drainage ditch scenario. Recovery times were assessed using the MASTEP population model. We simulated the population dynamics and pesticide effects in a Monte Carlo style by using median effective concentration values drawn from an arthropod species sensitivity distribution. In the tuber scenario, exposure to λ-cyhalothrin resulted in long-term effects, whereas exposure to the co-occurring compound fluazinam hardly resulted in (additional) effects. In the orchard scenario, 3 pesticides resulted in large effects just after exposure, but pulse exposures to these compounds did not coincide. The probabilities of effects for the single compounds added up for the combination; in contrast, the recovery times were not higher for the combination compared to those associated with exposure to the individual compounds. The conclusion from the present study's simulations is that exposure to the evaluated pesticide packages may lead to increased mortality probabilities and effect sizes of the combination, but does not lead to longer recovery times for populations with synchronized reproduction than when exposed to the individual compounds., (© 2013 SETAC.)

Background: The Surviving Sepsis Campaign recommends targeting a mean arterial pressure of at least 65 mm Hg during initial resuscitation of patients with septic shock. However, whether this blood-pressure target is more or less effective than a higher target is unknown., Methods: In a multicenter, open-label trial, we randomly assigned 776 patients with septic shock to undergo resuscitation with a mean arterial pressure target of either 80 to 85 mm Hg (high-target group) or 65 to 70 mm Hg (low-target group). The primary end point was mortality at day 28., Results: At 28 days, there was no significant between-group difference in mortality, with deaths reported in 142 of 388 patients in the high-target group (36.6%) and 132 of 388 patients in the low-target group (34.0%) (hazard ratio in the high-target group, 1.07; 95% confidence interval [CI], 0.84 to 1.38; P=0.57). There was also no significant difference in mortality at 90 days, with 170 deaths (43.8%) and 164 deaths (42.3%), respectively (hazard ratio, 1.04; 95% CI, 0.83 to 1.30; P=0.74). The occurrence of serious adverse events did not differ significantly between the two groups (74 events [19.1%] and 69 events [17.8%], respectively; P=0.64). However, the incidence of newly diagnosed atrial fibrillation was higher in the high-target group than in the low-target group. Among patients with chronic hypertension, those in the high-target group required less renal-replacement therapy than did those in the low-target group, but such therapy was not associated with a difference in mortality., Conclusions: Targeting a mean arterial pressure of 80 to 85 mm Hg, as compared with 65 to 70 mm Hg, in patients with septic shock undergoing resuscitation did not result in significant differences in mortality at either 28 or 90 days. (Funded by the French Ministry of Health; SEPSISPAM ClinicalTrials.gov number, NCT01149278.).

The objective of this study was to compare the number of drivers who self-reported cannabis use by questionnaires to the results of toxicological analysis. During roadside surveys, 2957 respondents driving a personal car or van completed a questionnaire to report their use of drugs and medicines during the previous two weeks and to indicate the time of their last intake. Cannabis was analyzed in oral fluid by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), in blood by gas chromatography-mass spectrometry (GC-MS). Frequencies in the time categories were calculated and compared with toxicological results. Diagnostic values were calculated for the time categories in which positive findings were to be expected (<4 h and <2 4h, respectively for tetrahydrocannabinol (THC) and delta9-tetrahydrocannabinol (THCCOOH) in blood, <12 h for THC in oral fluid). Most self-reported cannabis use was more than 12 h before driving. The sensitivity of the questionnaire was low, while the specificity and accuracy were high. Kappa statistics revealed a fair agreement between self-report and positive findings for THC in oral fluid and blood and moderate agreement with THCCOOH in blood. Self-report largely underestimates driving under the influence of cannabis, particularly recent cannabis use; therefore analysis of biological samples is necessary., (Copyright © 2013 John Wiley & Sons, Ltd.)

Our objective was to determine the presence of psychoactive substances in blood of drivers killed in road crashes in four European countries. Data from 1118 drivers of car and vans, killed between 2006 and 2009, were collected in Finland, Norway, Portugal and Sweden. The prevalence of any psychoactive substance ranged between 31 and 48%. Alcohol (≥ 0.1 g/L) was the most common finding, 87% had a blood alcohol concentration (BAC) ≥ .5 g/L. Benzodiazepines (1.8-13.3%) and amphetamines (0-7.4%) were the most prevalent psychoactive medicines and illicit drugs, respectively. Alcohol-drug and drug-drug combinations were rather prevalent. Differences in alcohol/drug findings seemed to reflect differences in use in the countries. More research should be done to develop preventive strategies to reduce the number of alcohol- and drug-related traffic accidents targeting at-risk groups, such as drivers with very high BACs and novice drivers.

The objective of this paper is to compare concentrations of alcohol, illicit, and medicinal drugs in seriously injured drivers and drivers selected randomly at the roadside. Blood samples were analyzed for alcohol, 17 medicinal drugs and 8 illicit psychoactive substances and/or their metabolites by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography mass spectrometry (GC-MS) in injured drivers admitted to the emergency departments of five hospitals in Belgium between January 2008 and May 2010 and in drivers randomly selected between January 2008 and September 2009. Three hundred and seventy-seven seriously injured drivers and 2750 roadside respondents were selected. In the roadside survey, out of the 203 concentrations above DRUID (Driving Under the Influence of Drugs, Alcohol and Medicines) cut-offs for medicinal drugs, 51% were in the therapeutic range, 46% infratherapeutic, and 2.5% supratherapeutic. In the seriously injured drivers, out of the 78 concentrations above DRUID cut-offs for medicinal drugs, these percentages were respectively 63%, 33%, and 4%. Significant differences were found in the distribution of concentrations for opioids, benzodiazepines, and Z-drugs. For the latter, while in the seriously injured drivers study most concentrations were therapeutic, in the roadside survey most were infratherapeutic. The opposite was observed for the opioids. Eight and 41% of the roadside respondents and injured drivers, respectively, had an alcohol concentration above 0.1 g/L, with higher concentrations found in the injured drivers. For illicit drugs, significant differences were found for amphetamine and cocaine, for which respectively lower and higher concentrations were observed in the blood samples taken in the roadside survey., (Copyright © 2012 John Wiley & Sons, Ltd.)

Aims: To illustrate (i) the criteria and the development of the DRUID categorization system, (ii) the number of medicines that have currently been categorized, (iii) the added value of the DRUID categorization system and (iv) the next steps in the implementation of the DRUID system., Methods: The development of the DRUID categorization system was based on several criteria. The following steps were considered: (i) conditions of use of the medicine, (ii) pharmacodynamic and pharmacokinetic data, (iii) pharmacovigilance data, including prevalence of undesirable effects, (iv) experimental and epidemiological data, (v) additional data derived from the patient information leaflet, existing categorization systems and (vi) final categorization. DRUID proposed four tiered categories for medicines and driving., Results: In total, 3054 medicines were reviewed and over 1541 medicines were categorized (the rest were no longer on the EU market). Nearly half of the 1541 medicines were categorized 0 (no or negligible influence on fitness to drive), about 26% were placed in category I (minor influence on fitness to drive) and 17% were categorized as II or III (moderate or severe influence on fitness to drive)., Conclusions: The current DRUID categorization system established and defined standardized and harmonized criteria to categorize commonly used medications, based on their influence on fitness to drive. Further efforts are needed to implement the DRUID categorization system at a European level and further activities should be undertaken in order to reinforce the awareness of health care professionals and patients on the effects of medicines on fitness to drive., (© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)

Thrombocytopenia is a very frequent disorder in the intensive care unit. Many etiologies should be searched, and therapeutic approaches differ according to these different causes. However, no guideline exists regarding optimum practices for these situations in critically ill patients. We present recommendations for the management of thrombocytopenia in intensive care unit, excluding pregnancy, developed by an expert group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF), the French Language Group of Paediatric Intensive Care and Emergencies (GFRUP) and of the Haemostasis and Thrombosis Study Group (GEHT) of the French Society of Haematology (SFH). The recommendations cover six fields of application: definition, epidemiology, and prognosis; diagnostic approach; therapeutic aspects; thrombocytopenia and sepsis; iatrogenic thrombocytopenia, with a special focus on heparin-induced thrombocytopenia; and thrombotic microangiopathy.

The objective of this study was to compare the number of drivers with drug concentrations above the legal cutoffs for driving under the influence of illicit substances in paired samples of blood and oral fluid. Between January 2008 and September 2009, 2,949 randomly selected drivers participated in a roadside survey. Each was asked to provide blood and oral fluid. Samples were analyzed for 11 illicit substances or metabolites by ultra-performance liquid chromatography-tandem mass spectrometry and gas chromatography-tandem mass spectrometry. Out of the 2,750 drivers who gave both blood and oral fluid, 28 (1.0%) had drug concentrations above the legal cutoff in blood and 71 (2.6%) were above the legal cutoff in oral fluid. Fifteen (7.5%) of the 199 drivers who gave an oral fluid sample but refused to provide blood tested positive, significantly more than drivers who provided both samples. Based on oral fluid analysis, 2.6 times more subjects tested positive for drugs compared to blood analysis. Those that refused to give a blood sample were 3 times more likely to test positive for drugs. Even in a survey that guaranteed total anonymity, people fearing a positive test result might have been more likely to refuse to give a blood sample.

The use of oral fluid (OF) as an alternative matrix for the detection of drugs of abuse has increased over the last decade, leading to the need for a rapid, simple, and reliable on-site OF testing device. Four on-site OF drug testing devices (Dräger DrugTest 5000, Cozart DDS, Mavand Rapid STAT, and Innovacon OrAlert) were evaluated on 408 volunteers at drug treatment centers. UPLC-MS-MS results were used as reference to determine sensitivity, specificity and accuracy for each device, applying Belgian legal confirmation cutoffs for benzoylecgonine, cocaine, and THC (10 ng/mL); morphine and 6-acetylmorphine (5 ng/mL); and amphetamine and 3,4-methylenedioxymethylamphetamine (25 ng/mL). Sensitivity for cocaine was 50%, 50%, 27%, and 11% for DrugTest, OrAlert, Rapid STAT, and DDS 806, respectively. For opiates, sensitivities were 84%, 73%, 77%, and 65%, respectively. For THC, the sensitivities were 81%, 23%, 43%, and 28%, respectively. For amphetamines, the sensitivities were 75%, 33%, 17%, and 67%, respectively. Specificity was >88% for opiates and THC, > 90% for amphetamines, and > 97% for cocaine. All tests showed good specificity. DrugTest had the highest sensitivity, although it was still low for some analytes.

The performance of eight on-site oral fluid drug screening devices was studied in Belgium, Finland and the Netherlands as a part of the EU-project DRUID. The main objective of the study was to evaluate the reliability of the devices for testing drivers suspected of driving under the influence of drugs (DUID). The performance of the devices was assessed by their ability to detect substances using cut-offs which were set at sufficiently low levels to allow optimal detection of positive DUID cases. The devices were evaluated for the detection of amphetamine(s), cannabis, cocaine, opiates and benzodiazepines when the relevant test was incorporated. Methamphetamine, MDMA and PCP tests that were included in some devices were not evaluated since there were too few positive samples. The device results were compared with confirmation analysis results in oral fluid. The opiates tests appeared to perform relatively well with sensitivity results between 69 and 90%. Amphetamines and benzodiazepines tests had lower sensitivity, although the DrugWipe test evaluated was promising for amphetamine. In particular, it is evident that the cannabis and cocaine tests of the devices still lack sensitivity, although further testing of the cocaine tests is desirable due to the low prevalence and low concentrations encountered in this study., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

We have designed and synthesized novel irreversible serine protease inhibitors containing aliphatic sulfonyl fluorides as an electrophilic trap. These substituted taurine sulfonyl fluorides derived from taurine or protected amino acids were conveniently synthesized from β-aminoethanesulfonyl chlorides using KF/18-crown-6 or from β-aminoethanesulfonates using DAST. Their potency of irreversible inhibition of serine proteases is described in different enzyme assays using chymotrypsin leading to binding affinities up to 22 μM., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A methodology is developed to quantify the uncertainty in a pesticide leaching assessment arising from the spatial variability of non-georeferenced parameters. A Monte Carlo analysis of atrazine leaching is performed in the Dyle river catchment (Belgium) with pesticide half-life (DT50) and topsoil organic matter (OM) content as uncertain input parameters. Atrazine DT50 is taken as a non-georeferenced parameter, so that DT50 values sampled from the input distribution are randomly allocated in the study area for every simulation. Organic matter content is a georeferenced parameter, so that a fixed uncertainty distribution is given at each location. Spatially variable DT50 values are found to have a significant influence on the amount of simulated leaching. In the stochastic simulation, concentrations exist above the regulatory level of 0.1 microg L(-1), but virtually no leaching occurs in the deterministic simulation. It is axiomatic that substance parameters (DT50, sorption coefficient, etc.) are spatially variable, but pesticide registration procedures currently ignore this fact. Including this spatial variability in future registration policies would have significant consequences on the amount and pattern of leaching simulated, especially if risk assessments are implemented in a spatially distributed way.

From 1986 to 1992, 88 patients with articular defects in the knee were treated with a perichondrial arthroplasty. In this study, we report on the results for 22 biopsies of grafted tissue with a mean follow-up of 21 months. Biopsies were obtained at routine arthroscopy after approximately 1 year or at arthroscopy or arthrotomy at a later stage when patients were operated on again because of recurrent complaints. Biopsies were taken only when a partial failure was present or when there was a clear failure resulting in fibrocartilage, a loose flap, or a loose body. The biopsies were analyzed histologically, biochemically for the amount of type-II collagen, and immunohistochemically with antibodies for types I, II, and X collagen. The well-being of the patients was investigated with use of the Hospital for Special Surgery knee score. The biopsies from 6 patients contained more than 50% hyaline cartilage. At arthroscopy, the mean relative amount of type-II collagen was 56% in the biopsies classified as good. The cartilage of the grafted area was macroscopically normal for eight of the 22 biopsies. Histological and biochemical analysis of biopsies from failed transplants showed fibrocartilage with mainly type-I collagen. These tissues were retrieved primarily from patients with additional abnormalities in the knee joint. It was concluded that adult human perichondrium is able to form hyaline-like cartilage in an isolated cartilage defect in an otherwise healthy knee.

A prospective study was done of the results of lateral release of the common extensor origin in sixty-three patients who had a tennis elbow. Fifty-seven of these patients were followed for a mean of fifty-nine months (range, fifty to sixty-five months). At the time of the operation, the extensor origin was macroscopically normal in all but six patients. Forty-seven (76 per cent) of the sixty-two patients who were evaluated at one year had no pain or only slight pain, whereas before the operation three patients (5 per cent) had had slight pain and sixty (95 per cent), severe pain. Of the fifty-seven patients who were re-examined after five years, fifty-two (91 per cent) had no pain or only slight pain. At one year, twenty patients (32 per cent) had an excellent over-all result; twenty-three (37 per cent), a good result; twelve (19 per cent), a fair result; and seven (11 per cent), a poor result. At five years, there were thirty-two excellent results (56 per cent), nineteen good results (33 per cent), four fair results (7 per cent), and two poor results (4 per cent). No association between the preoperative findings and the results of the operation was found. It was concluded that lateral extensor release, a relatively simple operation that can be performed in an outpatient setting, may be regarded at this time as the operative procedure with which other operations for tennis elbow should be compared.

Acute non-obstructive necrotizing enterocolitis in adults is characterized by pathological features: it is an intestinal necrosis beginning in the mucosa, without obstruction of the mesenteric vessels. The disease occurs in a variety of circumstances which may be roughly divided into infections and fall in proximal or distal mesenteric flow rate, the infectious and circulatory mechanisms often coexisting. Little information on the diagnosis is provided by clinical and paraclinical data. Management is medical and/or surgical; it includes alleviation of the symptoms in intensive care unit, attempts at producing local vasodilation whenever possible and resection of the intestinal segment affected. In many cases the diagnosis is made at exploratory laparotomy. The prognosis is poor; it depends on the patient's age, on the extent of the lesions which sometimes require wide intestinal resections, and on the time to diagnosis.

Oral anticoagulants (OC) prevent the activation by carboxylation of coagulation proteins. However this action also affects osteocalcin, or bone Gla-protein, a parameter of bone remodelling. Phosphorus and calcium metabolism, osteocalcin levels and bone mineral content were studied in twelve men aged under 60, and who had been taking OC for more than a year, in comparison with a paired group of nine controls with the same cardiovascular pathology but not taking anticoagulants. Osteocalcin levels were lower in the OC group (3.44 ng/ml) than in the control group (5.88 ng/ml) (p = 0.01). There was no significant difference in other phosphorus/calcium balance parameters nor in bone density between the two groups. No evidence was found of any osteopathy in the OC group, but the decrease in serum osteocalcin could result either from inhibition of its secretion or of its carboxylation, or from an action on the osteoblast.