Effects of a multifaceted intervention on cardiovascular risk factors in high-risk hypertensive patients: the ESCAPE trial, a pragmatic cluster randomized trial in general practice

BACKGROUND: Several observational studies on hypertensive patients have shown a gap between therapeutic targets recommended in guidelines and those achieved in daily practice. The ESCAPE trial aimed to determine whether a multifaceted intervention focused on general practitioners (GPs), could increase significantly the proportion of hypertensive patients at high risk in primary prevention who achieved all their recommended therapeutic targets. METHODS: A pragmatic, cluster randomized trial involving 257 GPs randomized by region. The GPs in the intervention group had a one-day training session and were given an electronic blood pressure measurement device and a short recommendation leaflet. Along with usual follow-up, they focused one consultation on hypertension and other cardiovascular risk factors every six months for two years. They also received feedback at baseline and at one year on their patients’ clinical and biological parameters. Main outcome measures were change in the proportion of patients achieving all their therapeutic targets and each individual therapeutic target at two years, and quality of life. RESULTS: 1,832 high-risk hypertensive patients were included. After two years, the proportion of patients achieving all their therapeutic targets increased significantly in both groups, but significantly more in the intervention group: OR (odds-ratio) 1.89, (95% confidence interval (CI) 1.09 to 3.27, P = 0.02). Significantly more patients achieved their blood pressure targets in the intervention group than in the usual care group: OR 2.03 (95% CI 1.44 to 2.88, P < 0.0001). Systolic and diastolic blood pressures decreased significantly more in the intervention group than in the usual care group, by 4.8 mmHg and 1.9 mmHg, respectively (P < 0.0001 for both). There were no significant difference changes in physical and mental quality of life between groups. CONCLUSION: An easy-to-perform, multifaceted intervention targeting only GPs increased significantly the proportion of high-risk hypertensive patients in primary prevention achieving their recommended therapeutic targets. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov, number NCT0034885

Perceptions about the sexuality of women with fibromyalgia syndrome: a phenomenological study

Aims: The aim of this study was to explore and understand the perceptions and experiences of women with fibromyalgia syndrome regarding their sexuality. Background: Fibromyalgia syndrome is a chronic pathology, which compromises a woman’s physical, mental and emotional health. Although concerns related to sexuality are commonly reported, research has tended to focus on the physical symptoms. Design: An interpretive qualitative research methodology using Gadamer’s philosophical hermeneutics was carried out. Methods: This qualitative study explores the sexuality of women with fibromyalgia syndrome. A focus group and semi-structured interviews were conducted with 13 women with fibromyalgia syndrome. Data were collected between April - June 2014. Participants were recruited until findings reached saturation. Findings: Three themes define the perception of sexuality for these women: (i) Physical impact: don’t touch, don’t look; (ii) Sexuality and identity: fighting against their loss; (iii) Impact on the relationship: sexuality as a way of connecting the couple. Conclusion: Despite limitations, sexuality is important for the identity and quality of life of women with fibromyalgia syndrome. Together with the physical symptomology, guilt, fear and a lack of understanding compromise the coping process. Women need the support of their partner, their socio-family environment and health professionals. Nurses can aid the successful adjustment to sexual problems related to fibromyalgia syndrome

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Selepressin in septic shock: A wake-up call for new drugs

International audienceEditorial Selepressin in septic shock: A wake-up call for new drugs Despite more than three decades of intensely investigating patients with septic shock, their mortality rate remains unacceptably high, particularly when the use of high-dose norepinephrine is required. An observational study reported mortality rates exceeding 80% for patients receiving intravenous norepinephrine doses above 1 mg/kg/min [1], and endogenous elevation of norepineph-rine serum concentrations has also been associated with increased mortality in patients with chronic congestive heart failure [2]. While one may assume that norepinephrine levels rise in response to increasing severity in patient condition, there is no proof of directionality. This association therefore suggests that treating patients with septic shock with exogenous norepineph-rine may in fact be counterproductive. Indeed, norepinephrine may not be the ideal medication for the treatment of septic shock. High-dose norepinephrine generates immunosuppression, thereby potentially contributing to the infectious process [3-5]. Norepinephrine increases blood pressure by triggering contraction of vascular smooth muscle. This effect is mediated through a-receptors that activate the inositol triphos-phate cascade, resulting in a massive release of intracellular calcium into the systemic circulation. However, a-receptors undergo downregulation in patients with severe inflammation. These are all good reasons for attempting to identify alternatives to norepinephrine. Vasopressin, one such alternative, is a neuroendocrine mediator released by the posterior hypophy-sis. Vasopressin modulates an intracellular chain of action similar to that of norepinephrine; i.e. a release of intracellular calcium through the phospholipase C signaling cascade [6]. However, it does so by activating V1a, V1b and V2 receptors. Contrary to norepinephrine, vasopressin can maintain activity in acidotic conditions [7]. Experimentally, in low doses, it can also act synergistically with norepinephrine [8]. To date, no randomised controlled trial (RCT) comparing treatment of patients with septic shock with norepinephrine versus vasopressin has revealed a survival difference [9,10]. Similarly , no study has found more deleterious effects when using either one of these vasopressors. Accordingly, vasopressin was endorsed as a second line vasopressor in the 2016 Surviving Sepsis Guidelines [11]. However, the clinical equivalence found in studies thus far has discouraged several European agencies from licensing vasopressin and/or approving reimbursement to healthcare facilities providing this medication, thereby effectively eliminating clinician discretion concerning medication choice. Vasopressin induces intracellular activation via V1a receptors, which triggers vasoconstriction. However, vasopressin also activates V1b and V2 receptors, both of which set in motion eventual extravascular fluid loss [6]. This effect is undesirable in septic shock where less fluid administration has been associated with increased survival. Selepressin, a newly available, short-acting vasopressin analogue, acts selectively on V1a receptors, thereby avoiding fluid retention. Animal models of ovine septic shock consistently show that administration of selepressin is accompanied by less net fluid gain than administration of arginine-vasopressin [12-14]. A pioneer randomised controlled study recently conducted in adult patients with early septic shock (n = 53) also confirmed lower net fluid gain among patients treated with selepressin versus those treated with placebo [15]. Observational studies show a clear and consistent association between net positive fluid balance and poorer outcomes in septic shock [16,17]. Therefore, it is logical to infer that the reduced fluid gain in septic patients treated with selepressin will also improve outcomes. In a well-designed multicentre trial conducted in 63 intensive care units across five countries (Belgium, Denmark, France, the Netherlands and the United States), Laterre et al. randomised 868 patients with septic shock to norepinephrine plus placebo (n = 283) or norepinephrine plus selepressin (n = 585) [18]. The primary endpoint sought was a composite 1.5-day reduction in ventilator-and vasopressor-free days. Assuming the baseline of ventilator-free days was 10 days and that of vasopressor-free days was 20 days, such a difference would represent a 7.5 to 15% improvement (power 91%, 1-tailed a-error 0.2). Treatment allocation and outcomes analyses were blinded. An adaptive platform was used for this study, enabling the analysis of several dosing regimens of selepressin, as well as patient recruitment until the sample sizes required for the study endpoints were met

The use of post-anaesthesia care units as a supply of ICU beds while maintaining scheduled surgery: a cross-sectional web-based feasibility survey in France

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Point of care ultrasonography: And now, where shall we go in perioperative medicine?

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Strategy focused on clinical parameters of microcirculation to resuscitate patients in septic shock: Do not forget any tools

International audienceEditorial Strategy focused on clinical parameters of microcirculation to resuscitate patients in septic shock: Do not forget any tools The current objective of initial resuscitation of patients with septic shock is the optimisation of general haemodynamic variables including heart rate, mean arterial blood pressure, cardiac output and cardiac preload using normalisation of arterial lactate as a marker of presumed success. However, microcirculatory blood flow can remain impaired despite restoration of macro-haemodynamic parameters. Ait-Oufella et al. clearly showed that persistence of skin mottling], an increased capillary refill time (CRT) and an increased toe-to-room temperature gradient were associated with worse patient outcomes. Similarly, Leone et al. reported that low oxygen tissue saturation (StO 2) was associated with poor outcomes in patients with septic shock. Few studies have assessed a strategy targeting the microcirculation..

Stratégie centrée sur les paramètres cliniques de microcirculation à la phase initiale du choc septique : ne négliger aucun outil

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Diamagnetically trapped arrays of living cells above micromagnets

International audienceCell arrays are of foremost importance for many applications in pharmaceutical research or fundamental biology. Although arraying techniques have been widely investigated for adherent cells, organization of cells in suspension has been rarely considered. The arraying of non-adherent cells using the diamagnetic repulsive force is presented. A planar arrangement of Jurkat cells is achieved at the microscale above high quality microfabricated permanent magnets with remanent magnetization of J(r) approximate to 1 T, in the presence of a paramagnetic contrast agent. The cytotoxicity of three Gd based contrast agents, Gd-DOTA, Gd-BOPTA and Gd-HP-DO3A, is studied. Among them, Gd-HP-DO3A appears to be the most biocompatible toward Jurkat cells. In close agreement with analytical simulations, diamagnetically 'suspended' cells have been successfully arrayed above square and honeycomb-like micromagnet arrays, which act as a "diamagnetophobic" surface. Living cell trapping is achieved in a simple manner using concentrations of Gd-HP-DO3A as low as 1.5 mM