Regulatory T-cell dysfunctions are associated with increase in tumor necrosis factor α in autoimmune hemolytic anemia and participate in Th17 polarization.

Warm autoimmune hemolytic anemia (wAIHA) is a rare acquired autoimmune disease mediated by antibodies targeting red blood cells. The involvement of CD4 T-helper cells has been scarcely explored, with most findings extrapolated from animal models. Here, we performed quantification of both effector T lymphocytes (Teff) and regulatory T cells (Treg), associated with functional and transcriptomic analyses of Treg in human wAIHA. We observed a shift of Teff toward a Th17 polarization concordant with an increase in serum interleukin-17 concentration that correlates with red blood cell destruction parameters, namely lactate dehydrogenase and bilirubin levels. A decrease in circulating Treg, notably effector Treg, associated with a functional deficiency, as represented by their decrease capability to inhibit Teff proliferation, were also observed. Treg deficiency was associated with a reduced expression of Foxp3, the master transcription factor known to maintain the Treg phenotype stability and suppressive functions. Transcriptomic profiling of Treg revealed activation of the tumor necrosis facto (TNF)-α pathway, which was linked to increased serum TNF-α concentrations that were twice as high as in controls. Treg transcriptomic profiling also suggested that post-translational mechanisms possibly accounted for Foxp3 downregulation and Treg dysfunctions. Since TNF-α participates in the rupture of immune tolerance during wAIHA, its inhibition could be of interest. To this end, the effects of fostamatinib, a SYK inhibitor, were investigated in vitro, and we showed that besides the inhibition of erythrocyte phagocytosis by monocytes, fostamatinib is also able to dampen TNF-α production, thus appearing as a promising multitargeting therapy in wAIHA (clinicaltrials gov. Identifier: NCT02158195).

PET/CT of cranial arteries for a sensitive diagnosis of giant cell arteritis.

OBJECTIVES: To investigate the performance of cranial PET/CT for the diagnosis of GCA. METHODS: All patients with a suspected diagnosis of GCA were prospectively enrolled in this study and had a digital PET/CT with evaluation of cranial arteries if they had not started glucocorticoids >72 h previously. The diagnosis of GCA was retained after at least 6 months of follow-up if no other diagnosis was considered by the clinician and the patient went into remission after at least 6 consecutive months of treatment. Cranial PET/CT was considered positive if at least one arterial segment showed hypermetabolism similar to or greater than liver uptake. RESULTS: For cranial PET/CT, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were 73.3%, 97.2%, 91.7% and 89.7%, respectively. For extracranial PET/CT, diagnostic performance was lower (Se = 66.7%, Sp = 80.6%, PPV = 58.8%, NPV = 85.3%). The combination of cranial and extracranial PET/CT improved overall sensitivity (Se = 80%) and NPV (NPV = 90.3%) while decreasing overall specificity (Sp = 77.8%) and PPV (PPV = 60%). CONCLUSION: Cranial PET/CT can be easily combined with extracranial PET/CT with a limited increase in examination time. Combined cranial and extracranial PET/CT showed very high diagnostic accuracy for the diagnosis of GCA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05246540.

Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration.

PURPOSE: To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm. DESIGN: Randomized, open-label, multicenter superiority study. PARTICIPANTS: Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (≤ 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium. METHODS: Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 µg], and 20% sulfur hexafluoride [SF6] tamponade) or PD (0.05 ml intravitreal tPA [50 µg] and 0.3 ml intravitreal pure SF6). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up. MAIN OUTCOME MEASURES: The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up. RESULTS: Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7-24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1-25.7 letters]; adjusted difference ß, 1.9 [-11.0; 14.9]; P = 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group. CONCLUSIONS: Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Impact of first COVID-19 lockdown on paediatric and adult haemophilia patients treated in a French Haemophilia Comprehensive Care Centre.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has created an unprecedented global health crisis. AIM: To investigate the impact of the 1st COVID-19 lockdown on haemophilia patients in terms of symptoms, management, medication adherence, mental health and lifestyle behaviours. METHODS: A prospective cross-sectional phone survey using a two-part questionnaire was conducted in haemophilia patients (adults and children) followed-up in a French Haemophilia Comprehensive Care Centre between May 5, 2020 and June 2, 2020 (CLEO CD study: NCT04390126). RESULTS: Among 284 haemophilia A or B patients with FVIII or FIX < 40% contacted for the study, 239 (84%) including 183 adults and 56 children participated to the survey. In 81% of children and 78% of adults, bleeding episodes remained unchanged or decreased. Medication adherence was 82.0% in adults and 98.2% in children. Non-adherence concerned haemostatic agents in six patients and analgesics in three. Overall, 67% of adults and 71% of children felt as good as before lockdown. In both adults and children, the three major changes in lifestyle behaviours were: increase in screen time (49% and 57%), decrease in physical activity (43% and 48%), and weight gain (32% and 27%), respectively. CONCLUSIONS: Encouraging results were observed in terms of haemophilia symptoms, medication adherence, and mental health. Conversely, a negative impact was observed on lifestyle behaviours in a cohort of French haemophilia patients during the 1st lockdown.

Septic patients without obvious signs of infection at baseline are more likely to die in the ICU.

OBJECTIVE: Early identification of sepsis is mandatory. However, clinical presentation is sometimes misleading given the lack of infection signs. The objective of the study was to evaluate the impact on the 28-day mortality of the so-called "vague" presentation of sepsis. DESIGN: Single centre retrospective observational study. SETTING: One teaching hospital Intensive Care Unit. SUBJECTS: All the patients who presented at the Emergency Department (ED) and were thereafter admitted to the Intensive Care Unit (ICU) with a final diagnosis of sepsis were included in this retrospective observational three-year study. They were classified as having exhibited either "vague" or explicit presentation at the ED according to previously suggested criteria. Baseline characteristics, infection main features and sepsis management were compared. The impact of a vague presentation on 28-day mortality was then evaluated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 348 included patients, 103 (29.6%) had a vague sepsis presentation. Underlying chronic diseases were more likely in those patients [e.g., peripheral arterial occlusive disease: adjusted odd ratio (aOR) = 2.01, (1.08-3.77) 95% confidence interval (CI); p = 0.028], but organ failure was less likely at the ED [SOFA score value: 4.7 (3.2) vs. 5.2 (3.1), p = 0.09]. In contrast, 28-day mortality was higher in the vague presentation group (40.8% vs. 26.9%, p = 0.011), along with longer time-to-diagnosis [18 (31) vs. 4 (11) h, p < 0.001], time-to-antibiotics [20 (32) vs. 7 (12) h, p < 0.001] and time to ICU admission [71 (159) vs. 24 (69) h, p < 0.001]. Whatever, such a vague presentation independently predicted 28-day mortality [aOR = 2.14 (1.24-3.68) 95% CI; p = 0.006]. CONCLUSIONS: Almost one third of septic patient requiring ICU had a vague presentation at the ED. Despite an apparent lower level of severity when initially assessed, those patients had an increased risk of mortality that could not be fully explained by delayed diagnosis and management of sepsis.

Mucosal-associated invariant T cells in Giant Cell Arteritis.

This study aimed to assess the implication of mucosal-associated invariant T (MAIT) cells in GCA. Blood samples were obtained from 34 GCA patients (before and after 3 months of treatment with glucocorticoids (GC) alone) and compared with 20 controls aged >50 years. MAIT cells, defined by a CD3+CD4-TCRγδ-TCRVα7.2+CD161+ phenotype, were analyzed by flow cytometry. After sorting, we assessed the ability of MAIT cells to proliferate and produce cytokines after stimulation with anti CD3/CD28 microbeads or IL-12 and IL-18. MAIT were stained in temporal artery biopsies (TAB) by confocal microscopy. MAIT cells were found in the arterial wall of positive TABs but was absent in negative TAB. MAIT frequency among total αß-T cells was similar in the blood of patients and controls (0.52 vs. 0.57%; P = 0.43) and not modified after GC treatment (P = 0.82). Expression of IFN-γ was increased in MAIT cells from GCA patients compared to controls (44.49 vs. 32.9%; P = 0.029), and not modified after 3 months of GC therapy (P = 0.82). When they were stimulated with IL-12 and IL-18, MAIT from GCA patients produced very high levels of IFN-γ and displayed a stronger proliferation compared with MAIT from controls (proliferation index 3.39 vs. 1.4; P = 0.032). In GCA, the functional characteristics of MAIT cells are modified toward a pro-inflammatory phenotype and a stronger proliferation capability in response to IL-12 and IL-18, suggesting that MAIT might play a role in GCA pathogenesis. Our results support the use of treatments targeting IL-12/IL-18 to inhibit the IFN-γ pathway in GCA.

[A caregiver-person with schizophrenia partnership to improve oral health education] / Un partenariat patients schizophrènes-soignants pour conduire un programme d'éducation en santé orale.

INTRODUCTION: Poor oral health in persons with schizophrenia is a major public health issue affecting 600,000 people in France. The aim of this article was to present the different stages in the development of a specific oral health educational program for persons with schizophrenia. It takes into account experimental knowledge of these persons and presents the results of the feasibility study. PATIENTS AND METHOD: The focus group method was applied to a group of health professionals and users to highlight an exploratory corpus in order to develop an oral health educational program. An expert group including persons with schizophrenia among others validated the fields and tools of this program. A feasibility study was then conducted in a control group of 7 persons with schizophrenia. RESULTS: Altogether, 26 persons participated in this feasibility study. The main fields investigated by the expert group aimed to promote personal responsibility for one's health, to improve access to the healthcare system and to promote the global management of health. The feasibility study showed the ability of this program to change persons with schizophrenia representations and knowledge of this health problem. Most educational tools were considered relevant. CONCLUSION: An oral health educational program was built as part of a caregiver-persons with schizophrenia partnership and showed its feasibility. A multicentric randomized trial is currently ongoing to assess the efficacy of this program with a high level of proof.

Screening for Retinopathy of Prematurity: Insight into Optimizing Screening.

PURPOSE: To determine the factors influencing the time from preterm birth and retinopathy of prematurity (ROP) detection to optimize the timing of the initial screening. METHODS: This multicenter retrospective study enrolled preterm infants born before 32 weeks of gestational age (GA) and/or weighing less than 1,500 g between January 1, 2011, and December 31, 2015. ROP screening was performed using fundus photography with a wide-field camera. Population and follow-up characteristics were recorded. RESULTS: Among the 1,266 preterm infants observed, 795 were retained for analysis. One hundred seventy-four (21.6%) cases of ROP were detected with the first examination performed at 32.3 ± 1.6 weeks of postmenstrual age (PMA) and 5.4 ± 1.0 weeks of postnatal age (PNA). The first signs of ROP were detected at 34.0 ± 1.9 weeks of PMA and 7.2 ± 1.8 weeks of PNA, respectively. In the multivariate analysis, an older GA, a longer duration of mechanical ventilation, and a lower birth weight were correlated with a longer time between preterm birth and ROP detection (p < 0.0001, p < 0.0001, and p = 0.0359, respectively). CONCLUSION: The first examination for ROP screening should be individualized to fit the first screening examination as closely as possible to the first signs of ROP in order to avoid unnecessary examinations without missing ROP.

Cerebral Infarct Topography and Early Outcome after Surgery for Symptomatic Carotid Stenosis: A Multicentre Study.

INTRODUCTION: Although carotid stenosis can cause both territorial and border-zone (BZ) cerebral infarcts (CI), the influence of CI topography on postoperative complications after surgery remains unclear. We compared early outcomes after endarterectomy on the basis of CI location: territorial (T group) or BZ group. MATERIAL AND METHODS: During the period between 2009 and 2013, ischaemic stroke patients who had undergone surgery for symptomatic carotid stenosis were identified from prospective databases from 3 French centres. The outcome was the identification of a combined stroke/death rate 30 days after endarterectomy. RESULTS: Two hundred and eighty-nine patients were included, 216 (74.7%) in the T group and 73 (25.3%) in the BZ group. The mean degree of stenosis was comparable in the 2 groups (78 ± 12% in the T group vs. 80 ± 12% in the BZ group, p = 0.105), with, however, more sub-occlusions (stenosis >90%) in the BZ group (38.4 vs. 23.1%, p = 0.012). The mean time between the time CI developed and the time surgery was performed was 19.6 ± 24.8 days, with a majority of patients being operated upon within 2 weeks following the formation of CI (66.7% in the T group vs. 60.3% in the BZ group, p = 0.322). The combined endpoint was significantly more frequent in the BZ group (9.6 vs. 1.9%, p = 0.003), with 4 ischaemic strokes and 3 deaths. In multivariate analysis, BZ CI was an independent predictor of postoperative stroke or death at 30 days (HR 4.91-95% CI [1.3-18.9], p = 0.020). CONCLUSION: BZ infarcts carry a greater risk of postoperative complications after carotid surgery, thus suggesting that topography of the CI should be considered in the decision-making process regarding surgery.

Preferential splenic CD8(+) T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia.

The pathogenic role of B cells in immune thrombocytopenia (ITP) has justified the therapeutic use of anti-CD20 antibodies such as rituximab (RTX). However, 60% of ITP patients do not respond to RTX. To decipher the mechanisms implicated in the failure of RTX, and because the spleen plays a well-recognized role in ITP pathogenesis, 12 spleens from ITP patients who had been nonresponders to RTX therapy were compared with 11 spleens from RTX-untreated ITP patients and 9 controls. We here demonstrate that in RTX-nonresponder ITP patients, preferential Th1 and Tc1 T lymphocyte polarizations occur, associated with an increase in splenic effector memory CD8(+) T-cell frequency. Moreover, in the RTX- nonresponder patient group, the CD8(+) T-cell repertoire displays a restricted pattern. In the blood, the phenotype of CD8(+) T cells before and after RTX treatment is not modified in responders or nonresponders. Altogether, these results demonstrate for the first time an activation of splenic CD8(+) T cells in ITP patients who did not respond to RTX and suggest their involvement in platelet destruction in these patients.

Effectiveness of a Therapeutic Educational Oral Health Program for Persons with Schizophrenia: A Cluster Randomized Controlled Trial and Qualitative Approach.

BACKGROUND: The oral health of people with schizophrenia (PWS) is very poor, suggesting a need for oral health promotion programmes with a high level of evidence. The aim of the EBENE study (Clinicaltrials.gov: NCT02512367) was to develop and evaluate the effectiveness of a multidisciplinary therapeutic educational programme in oral health (TEPOH) for PWS. METHODS: A multicentre cluster randomised controlled trial, with outpatient psychiatry centres as the unit of randomisation, was designed to compare the effectiveness of TEPOH (intervention group) versus standard care (control group). The trial was conducted in 26 outpatient psychiatry centres in France (14 in the intervention group, 12 in the control group). Eligible patients with a diagnosis of schizophrenia were enroled between 2016 and 2020 and followed for 6 months. The TEPOH group received a multicomponent intervention (comprising an introductory session, three educational sessions, and a debriefing session). The primary endpoint was the evaluation of periodontal disease as a community periodontal index (CPI) score ≥ 3 at Month 6. The trial was completed using a qualitative approach based on semi-structured interviews with caregivers conducted between July 2018 and December 2019. The trial was stopped early due to difficulties in recruiting patients. RESULTS: Overall, 81 patients (of 250 planned) were included, and 54 patients completed the trial: 40 in the TEPOH group and 14 in the control group. At baseline, the percentage of CPI ≥ 3 was 42.5% in the TEPOH group and 9.1% in the control group. At Month 6, the percentage of CPI ≥ 3 was 20% in the TEPOH group and 14.3% in the control group. The qualitative evaluation underlined that the professionals emphasised the "seriousness" and "assiduity" of the patients' participation in this programme and that the TEPOH reinforced carers' investment in oral hygiene. It also highlighted structural factors (lack of resources for professionals, lack of teeth in PWS, COVID-19 pandemic) that may have exacerbated the difficulties with enrolment and follow-up. CONCLUSIONS: The effectiveness of this TEPOH, developed for PWS as part of the EBENE study, has not been demonstrated. Certain aspects of the programme's content and implementation need to be reconsidered. In particular, an adapted subjective measurement scale should be developed.

Efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing consumption in patients with alcohol use disorders (ALCOSTIM): study protocol for a randomized controlled trial.

BACKGROUND: The number of people with an alcohol use disorder (AUD) was recently estimated to be 63.5 million worldwide. The global burden of disease and injury attributable to alcohol is considerable: about 3 million deaths, namely one in 20, were caused by alcohol in 2015. At the same time, AUD remains seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation could play an important role. The early results of studies using repetitive transcranial magnetic stimulation (rTMS) suggest that stimulations delivered to the dorsolateral prefrontal cortex significantly reduce cravings and improve decision-making processes in various addictive disorders. We therefore hypothesize that rTMS could lead to a decrease in alcohol consumption in patients with AUD. METHODS/DESIGN: We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy of rTMS on alcohol reduction in individuals diagnosed with AUD. The study will be conducted in 2 centers in France. Altogether, 144 subjects older than 18 years and diagnosed with AUD will be randomized to receive 5 consecutive twice-daily sessions of either active or sham rTMS (10 Hz over the right DLPFC, 2000 pulses per day). The main outcomes of the study will be changes in alcohol consumption within the 4 weeks after the rTMS sessions. Secondary outcome measures will include changes in alcohol consumption within the 24 weeks, alcohol cravings, clinical and biological improvements, effects on mood and quality of life, and cognitive and safety assessments, and, for smokers, an assessment of the effects of rTMS on tobacco consumption. DISCUSSION: Several studies have observed a beneficial effect of rTMS on substance use disorders by reducing craving, impulsivity, and risk-taking behavior and suggest that rTMS may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm this hypothesis. The results from this large randomized controlled trial will give a better overview of the therapeutic potential of rTMS in AUD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04773691. Registered on 26 February 2021 https://clinicaltrials.gov/ct2/show/NCT04773691?term=trojak&draw=2&rank=5 .

COVID-19 Lockdown in Patients with Chronic Diseases: A Cross-Sectional Study.

Background: We aimed to investigate the impact of the first COVID-19 lockdown on medication adherence, physician access, lifestyle behaviours, and mental health in patients with chronic conditions. Methods: A cross-sectional phone survey was conducted in 1274 housebound adults recruited from 8 regional chronic disease cohorts (CLEO CD study: NCT04390126). Results: Medication adherence was 97%; 305 (41%) patients declared that at least one scheduled visit with a physician was missed during the first lockdown. The main changes in lifestyle behaviours were deterioration in sleep time (duration and/or quality; 71%), increase in screen time (46%), and decrease in physical activity (46%). Nineteen percent experienced psychological distress (Kessler-6 score ≥ 5). An urban living place (OR, 1.76 vs. rural; 95% CI, 1.32−2.33; p = 10−4), worse self-reported mental health (OR, 1.62 vs. about the same or better; 95% CI, 1.17−2.25; p = 0.003), and a K6 score ≥ 5 (OR, 1.52 vs. <5; 95% CI, 1.05−2.21; p = 0.03) were independent factors associated with at least one unhealthy behaviour. Conclusions: Encouraging results were observed in terms of medication adherence. Caution is needed in chronic disease patients living in urban places as well as those presenting psychological distress and worse self-reported mental health to reduce unhealthy behaviours.

Levosimendan in venoarterial ECMO weaning. Rational and design of a randomized double blind multicentre trial.

AIMS: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used in circulatory failure. The main indications are cardiogenic shock, post-cardiotomy cardiac failure, and refractory cardiac arrest. However, VA-ECMO weaning is particularly challenging, and weaning failure is reported to be as high as 50%, with increased related mortality. Levosimendan is a novel long acting effect inodilator used in cardiogenic shock and terminal heart failure decompensation. Levosimendan use in VA-ECMO patients seems to reduce weaning failure regardless of the initial aetiology and to reduce mortality when administrated early after VA-ECMO initiation. However, studies are limited to retrospective analyses and reported case series. The aim of the WEANILEVO trial is to evaluate whether administration of levosimendan before VA-ECMO weaning is associated with a reduced rates of weaning failure and recourse to other temporary circulatory support. METHODS AND RESULTS: WEANILEVO is a randomized, prospective, multicentre, double-blind, parallel-group, controlled trial. One hundred eighty patients will be enrolled if they had acute circulatory heart failure treated with VA-ECMO and for whom weaning is expected within 48 h. The study drugs are either levosimendan (0.2 µg/kg/min for 24 h) or a placebo. The primary endpoint of the trial is the absence of VA-ECMO weaning, recourse to another VA-ECMO, or other temporary circulatory assistance or death within 7 days of VA-ECMO weaning. CONCLUSIONS: Levosimendan use in VA-ECMO appears to be beneficial for reducing weaning failure and mortality. The results of WEANILEVO should significantly influence decisions regarding the use of levosimendan for VA-ECMO weaning.

Impact of lockdown on patients with congestive heart failure during the coronavirus disease 2019 pandemic.

AIMS: Cardiovascular co-morbidities like congestive heart failure (CHF) alter the course of coronavirus disease 2019. Factors associated with the outbreak and lockdown can exacerbate CHF. METHODS AND RESULTS: We analysed the answers of 124 randomly selected CHF outpatients (mean age 71.0 ± 14.0 years, 60.5% male) interviewed by phone during the sixth and seventh weeks of the lockdown. Most patients were treated for New York Heart Association class II (38.7%) and reduced ejection fraction HF (70.2%). Psychological distress (Kessler 6 score ≥ 5) was common (18.5%), and 21.8% felt worse than before the lockdown. Few patients (n = 10) adjusted their intake of HF medications, always on medical prescription. Decreased physical activity was common (41.9%) and more frequent in women (P = 0.025) and urban dwellers (P = 0.009). Almost half of respondents (46.0%) declared increased screen time, but only few declared more alcohol intake (4.0%). Weight gain was common (27.4%), and 44.4% of current smokers increased tobacco consumption. Adherence to recommended salt or fluid intake restrictions was reduced in 14.5%. Increase in HF symptoms was commonly reported (21.8%) and tended to be higher in women than in men (P = 0.074). Of the 23 patients who had a phone teleconsultation during the pandemic, 16 had initially planned an in-person consultation that they switched for teleconsultation. CONCLUSIONS: During the lockdown, psychological distress and decreased well-being were common in CHF outpatients, and there was an increase in unhealthy lifestyle behaviours. These changes may negatively impact short-term and long-term prognoses. Medication adherence was maintained, and limitations in access to care were partly counterbalanced by use of telehealth.

Corporeal Compression at the Onset of Septic shock (COCOONs): a compression method to reduce fluid balance of septic shock patients.

Fluid overload in septic intensive care unit (ICU) patients is common and strongly associated with poor outcome. There is currently no treatment for capillary leak, which is mainly responsible for high positive fluid balance (FB) in sepsis. We hypothesized that increasing interstitial pressure with extensive corporeal compression would reduce FB. The objective of this study was to evaluate the feasibility, efficacy, and safety of a compression treatment during sepsis. This pilot, two-center, single-arm trial enrolled critically ill, non-surgical, septic patients receiving mechanical ventilation. The therapeutic intervention was the early application of compression bandages on more than 80% of the body surface. The primary outcome was negative net FB on day 7. The primary endpoint was reached in 29 of 45 patients (64%) with available data, for a planned objective of 26. By day 4, cumulative FB was 7280 ml [3300-9700]. SOFA- and aged-matched patients from a historical cohort had a significantly higher FB at 1, 2 and 7 days. Tolerance was good, although low-stage pressure ulcers were observed in 16 patients (26%). No effect on intra-abdominal pressure or respiratory plateau pressure was observed. In conclusion, corporeal compression demonstrated potential efficacy in limiting FB during septic shock, with acceptable feasibility and tolerance.

Trisodium citrate 4% versus heparin as a catheter lock for non-tunneled hemodialysis catheters in critically ill patients: a multicenter, randomized clinical trial.

BACKGROUND: Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent catheter dysfunction and infection with catheter locks remain controversial. METHODS: In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality. RESULTS: Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3-10) in the citrate group and 5 days (IQR 3-11) in the heparin group (p = 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups. CONCLUSIONS: In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups. Trial registration Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.

Study protocol: a cluster randomized controlled trial to assess the effectiveness of a therapeutic educational program in oral health for persons with schizophrenia.

BACKGROUND: Schizophrenia is a severe mental disorder that affects 1 % of the world's population, including 600,000 people in France. Persons with schizophrenia (PWS) have excess mortality (their life expectancy is reduced by 20 %) and excess morbidity. In addition, such persons may have a large number of missing or decayed teeth. Dental caries and periodontal measurement indexes are often twice as high as the level found in the general population. Poor oral health can also affect quality of life and oral health is inseparable from general health. The management of oral health problems needs a multidisciplinary approach. According to the World Health Organization, the aim of therapeutic education (TE) is to help patients take care of themselves and to improve empowerment and recovery. In this educational approach, it is important to take into account the patient's personal experience. Though rarely investigated, the personal experience of PWS in oral health quality of life (OHRQoL) must be used to build a therapeutic educational programme in oral health (TEPOH) in a multidisciplinary approach, and the effectiveness of this program must be evaluated. METHODS/DESIGN: We report the protocol of a randomized controlled cluster study. This study will be conducted in twelve hospitals in France. We hypothesized that a decrease of 20 % in the proportion of patients with CPI ≥ 3 would establish the effectiveness of TEPOH. Therefore, 12 hospitals will be randomly allocated to either TEPOH or no TEPOH. Altogether, they will have to recruit 230 PWS, who will be randomly allocated with a ratio of 1:1 to one of two conditions: control without intervention versus the group benefitting from TEPOH. DISCUSSION: If successful, the study will generate methodologically sound results that provide knowledge on the effectiveness of a TEP in oral health for PWS. The results can be used to promote OHRQoL in a global health approach and develop appropriate strategies to encourage and facilitate financial support for healthcare, the multidisciplinary treatment of dental disorders, and the development of training in oral and mental health for caregivers. Trial registration Clinical Trials Gov NCT02512367. Date registered 19 July, 2015.

Efficacy of transcranial direct current stimulation (tDCS) in reducing consumption in patients with alcohol use disorders: study protocol for a randomized controlled trial.

BACKGROUND: Approximately 15 million persons in the European Union and 10 million persons in the USA are alcohol-dependent. The global burden of disease and injury attributable to alcohol is considerable: worldwide, approximately one in 25 deaths in 2004 was caused by alcohol. At the same time, alcohol use disorders remain seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation may play a prominent role. The early results of studies using transcranial direct current stimulation found that stimulations delivered to the dorsolateral prefrontal cortex result in a significant reduction of craving and an improvement of the decision-making processes in various additive disorders. We, therefore, hypothesize that transcranial direct current stimulation can lead to a decrease in alcohol consumption in patients suffering from alcohol use disorders. METHODS/DESIGN: We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial, to evaluate the efficacy of transcranial direct current stimulation on alcohol reduction in patients with an alcohol use disorder. The study will be conducted in 14 centers in France and Monaco. Altogether, 340 subjects over 18 years of age and diagnosed with an alcohol use disorder will be randomized to receive five consecutive twice-daily sessions of either active or placebo transcranial direct current stimulation. One session consists in delivering a current flow continuously (anode F4; cathode F3) twice for 13 minutes, with treatments separated by a rest interval of 20 min. Efficacy will be evaluated using the change from baseline (alcohol consumption during the 4 weeks before randomization) to 24 weeks in the total alcohol consumption and number of heavy drinking days. Secondary outcome measures will include alcohol craving, clinical and biological improvements, and the effects on mood and quality of life, as well as cognitive and safety assessments, and, for smokers, an assessment of the effects of transcranial direct current stimulation on tobacco consumption. DISCUSSION: Several studies have reported a beneficial effect of transcranial direct current stimulation on substance use disorders by reducing craving, impulsivity, and risk-taking behavior, and suggest that transcranial direct current stimulation may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm the hypothesis. Results from this large randomized controlled trial will give a better overview of the therapeutic potential of transcranial direct current stimulation in alcohol use disorders. TRIAL REGISTRATION: Clinical Trials Gov, NCT02505126 (registration date: July 15 2015).