Use of 5-ALA fluorescence-guided surgery versus white-light conventional microsurgery for the resection of newly diagnosed glioblastomas (RESECT study): a French multicenter randomized phase III study.

OBJECTIVE: Only one phase III prospective randomized study, published in 2006, has assessed the performance of 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) for glioblastoma resection. The aim of the RESECT study was to compare the onco-functional results associated with 5-ALA fluorescence and with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care. METHODS: This was a phase III prospective randomized single-blinded study, involving 21 French neurosurgical centers, comparing 5-ALA FGS with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care, including neuronavigation use and postoperative radiochemotherapy. Randomization was performed in a 1:1 ratio stratified by institution. 5-ALA (20 mg/kg) or placebo (ascorbic acid) was administered orally 3-5 hours before the incision. The primary endpoint was the rate of gross-total resection (GTR) blindly assessed by an independent committee. Patients without a confirmed pathological diagnosis of glioblastoma or with unavailable postoperative MRI studies were excluded from the per-protocol analysis. RESULTS: Between March 2013 and August 2016, a total of 171 patients were assigned to the 5-ALA fluorescence group (n = 88) or to the placebo group (n = 83). Twenty-four cases were excluded because the WHO histological criteria of grade 4 glioma were not met. The proportion of GTR was significantly higher in the 5-ALA fluorescence group (53/67, 79.1%) than in the placebo group (33/69, 47.8%; p = 0.0002). After adjustment for age, preoperative Karnofsky Performance Scale score, and tumor location, GTR was still associated with 5-ALA fluorescence (OR 4.13 [95% CI 1.94-8.79]). The mean 7-day postoperative Karnofsky Performance Scale score (≥ 80% in 49/71, 69.0% [5-ALA group]; 50/71, 70.4% [placebo group], p = 0.86) and the proportion of patients with a worsened neurological status 3 months postoperatively (9/68, 13.2% [5-ALA group]; 9/70, 12.9% [placebo group], p = 0.95) were similar between groups. Adverse events related to 5-ALA intake were rare and consisted of photosensitization in 4/87 (4.6%) patients and hepatic cytolysis in 1/87 (1.1%) patients. The 6-month PFS (70.2% [95% CI 57.7%-79.6%] and 68.4% [95% CI 55.7%-78.1%]; p = 0.39) and 24-month OS (30.1% [95% CI 18.9%-42.0%] and 37.7% [95% CI 25.8%-49.5%]; p = 0.89) did not significantly differ. In multivariate analysis, GTR was an independent predictor of PFS (hazard ratio 0.56 [95% CI 0.36-0.86], p = 0.008) and OS (hazard ratio 0.65 [95% CI 0.42-1.01], p = 0.05). The use of 5-ALA FGS generates a significant extra cost of 2732.36€ (95% CI 1658.40€-3794.11€). CONCLUSIONS: The authors found that 5-ALA FGS is an easy-to-use, cost-effective, and minimally time-consuming technique that safely optimizes the extent of resection in patients harboring glioblastoma amenable to a large resection.

Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Cancer: 24-Month Results of the RSR1 Phase 1 Dose Escalation Study.

PURPOSE: Stereotactic body radiation therapy (SBRT) has become a new therapeutic option for primary renal cell carcinoma. However, treatment doses lack consistency in the literature. The primary objective of this study was to determine the maximum tolerated dose for renal cancer SBRT. METHODS AND MATERIALS: This phase 1 multicentric dose-escalation study assessed 4 dose levels: 8 Gy × 4, 8 Gy × 5, 10 Gy × 4, and 12 Gy × 4. The primary objective of this study was to determine the maximal tolerated dose, defined by the occurrence of dose-limiting toxicity was defined as any acute side effect of grade ≥4 based on the Common Terminology Criteria for Averse Events, version 4.0. RESULTS: From October 2010 to September 2017, 13 patients were enrolled. The median follow-up was 23 months. There was no dose-limiting toxicity in our study, and the highest dose was reached successfully. No acute or late toxic effects above grade 2 were seen. There was no significant alteration of renal function after treatment. At 24 months, 2 patients had partial response and the others had stable disease. CONCLUSIONS: After 24 months of follow-up, no dose-limiting toxicity was seen at any of the prescribed dose levels in our study. The findings suggest that our last dose level of 48 Gy in 4 12-Gy fractions can be considered safe and can be used in further studies.

Management and Outcome of COVID-19 Positive and Negative Patients in French Emergency Departments During the First COVID-19 Outbreak: A Prospective Controlled Cohort Study.

INTRODUCTION: Few studies have investigated the management of COVID-19 cases from the operational perspective of the emergency department (ED), We sought to compare the management and outcome of COVID-19 positive and negative patients who presented to French EDs. METHODS: We conducted a prospective, multicenter, observational study in four EDs. Included in the study were adult patients (≥18 years) between March 6-May 10, 2020, were hospitalized, and whose presenting symptoms were evocative of COVID-19. We compared the clinical features, management, and prognosis of patients according to their confirmed COVID-19 status. RESULTS: Of the 2,686 patients included in this study, 760 (28.3%) were COVID-19 positive. Among them, 364 (48.0%) had hypertension, 228 (30.0%) had chronic cardiac disease, 186 (24.5%) had diabetes, 126 (16.6%) were obese, and 114 (15.0%) had chronic respiratory disease. The proportion of patients admitted to intensive care units (ICU) was higher among COVID-19 positive patients (185/760, 24.3%) compared to COVID-19 negative patients (206/1,926, 10.7%; P <0.001), and they required mechanical ventilation (89, 11.9% vs 37, 1.9%; P <0.001) and high-flow nasal cannula oxygen therapy (135, 18.1% vs 41, 2.2%; P < 0.001) more frequently. The in-hospital mortality was significantly higher among COVID-19 positive patients (139, 18.3% vs 149, 7.7%; P <0.001). CONCLUSION: Emergency departments were on the frontline during the COVID-19 pandemic and had to manage potential COVID-19 patients. Understanding what happened in the ED during this first outbreak is crucial to underline the importance of flexible organizations that can quickly adapt the bed capacities to the incoming flow of COVID-19 positive patients.

Changes over time in anxiety, depression, and stress symptoms among healthcare workers in French emergency departments during the first COVID-19 outbreak.

STUDY OBJECTIVE: Assess the changes in anxiety, depression, and stress levels over time and identify risk factors among healthcare workers in French emergency departments (EDs) during the first COVID-19 outbreak. METHOD: A prospective, multicenter study was conducted in 4 EDs and an emergency medical service (SAMU). During 3 months, participants completed fortnightly questionnaires to assess anxiety, depression, and stress using the Hospital Anxiety and Depression and the Chamoux-Simard scale. The changes in anxiety, depression, and stress levels over time were modelled by a linear mixed model including a period effect and a continuous time effect within periods. RESULTS: A total of 211 respondents (43.5 %) completed the survey at inclusion. There was a decrease in mean anxiety (from 7.33 to 5.05, p < 0.001), mean depression (from 4.16 to 3.05, p = 0.009), mean stress at work (from 41.2 to 30.2, p = 0.008), and mean stress at home (from 33.0 to 26.0, p = 0.031) at the beginning of each period. The mean anxiety level was higher for administrative staff (+0.53) and lower for paramedics (-0.61, p = 0.047) compared to physicians. The anxiety level increased with the number of day and night shifts (0.13/day, p < 0.001, 0.12/night, p = 0.025) as did stress at work (1.6/day, p < 0.001, 1.1/night, p = 0.007). Reassigned healthcare workers were at higher risk of stress particularly compared to SAMU workers (stress at work: p = 0.015, at home: p = 0.021, in life in general: p = 0.018). CONCLUSION: Although anxiety, depression, and stress decreased over time, anxiety was higher among physicians and administrative staff. Reassignment and working hours were identified as potential risk factors for mental health distress in EDs.

Cardiac involvement in pediatric hemolytic uremic syndrome.

BACKGROUND: Cardiac involvement is a known but rare complication of pediatric hemolytic uremic syndrome (HUS). We conducted a nationwide observational, retrospective case-control study describing factors associated with the occurrence of myocarditis among HUS patients. METHODS: Cases were defined as hospitalized children affected by any form of HUS with co-existent myocarditis in 8 French Pediatric Intensive Care Units (PICU) between January 2007 and December 2018. Control subjects were children, consecutively admitted with any form of HUS without coexistent myocarditis, at a single PICU in Lyon, France, during the same time period. RESULTS: A total of 20 cases of myocarditis were reported among 8 PICUs, with a mean age of 34.3 ± 31.9 months; 66 controls were identified. There were no differences between the two groups concerning the season and the typical, Shiga toxin-producing Escherichia coli (STEC-HUS), or atypical HUS (aHUS). Maximal leukocyte count was higher in the myocarditis group (29.1 ± 16.3G/L versus 21.0 ± 9.9G/L, p = 0.04). The median time between admission and first cardiac symptoms was of 3 days (range 0-19 days), and 4 patients displayed myocarditis at admission. The fatality rate in the myocarditis group was higher than in the control group (40.0% versus 1.5%, p < 0.001). Thirteen (65%) children from the myocarditis group received platelet transfusion compared to 19 (29%) in the control group (p = 0.03). CONCLUSION: Our study confirms that myocarditis is potentially lethal and identifies higher leukocyte count and platelet transfusion as possible risk factors of myocarditis. A higher resolution version of the Graphical abstract is available as Supplementary information.

Ultrasound guidance for urgent arterial and venous catheterisation: randomised controlled study.

BACKGROUND: Haemodynamically unstable patients often require arterial and venous catheter insertion urgently. We hypothesised that ultrasound-guided arterial and venous catheterisation would reduce mechanical complications. METHODS: We performed a prospective RCT, where patients requiring both urgent arterial and venous femoral catheterisation were randomised to either ultrasound-guided or landmark-guided catheterisation. Complications and characteristics of catheter insertion (procedure duration, number of punctures, and procedure success) were recorded at the time of insertion (immediate complications). Late complications were investigated by ultrasound examination performed between the third and seventh days after randomisation. Primary outcome was the proportion of patients with at least one mechanical complication (immediate or late), by intention-to-treat analysis. Secondary outcomes included success rate, procedure time, and number of punctures. RESULTS: We analysed 136 subjects (102 [75%] male; age range: 27-62 yr) by intention to treat. The proportion of subjects with one or more complications was lower in 22/67 (33%) subjects undergoing ultrasound-guided catheterisation compared with landmark-guided catheterisation (40/69 [58%]; odds ratio: 0.35 [95% confidence interval: 0.18-0.71]; P=0.003). Ultrasound-guided catheterisation reduced both immediate (27%, compared with 51% in the landmark approach group; P=0.004) and late (10%, compared with 23% in the landmark approach group; P=0.047) complications. Ultrasound guidance also reduced the proportion of patients who developed deep vein thrombosis (4%, compared with 22% following landmark approach; P=0.012), and achieved a higher procedural success rate (96% vs 78%; P=0.004). CONCLUSIONS: An ultrasound-guided approach reduced mechanical complications after urgent femoral arterial and venous catheterisation, while increasing procedural success. CLINICAL TRIAL REGISTRATION: NCT02820909.

Short- and long-term prognosis of acute critically ill patients with systemic rheumatic diseases: A retrospective multicentre study.

ABSTRACT: Patients with systemic rheumatic disease (SRD) share the risks of multi-organ flare-up, cardiovascular diseases, and immunosuppression. Such situations can lead to an acute critical illness. The present study describes the clinical features of SRD patients admitted to the intensive care unit (ICU) and their short- and long- term mortality.We performed a multicentre retrospective study in 10 French ICU in Lyon, France. Inclusion criteria were SRD diagnosis and admission for an acute organ failure. The primary endpoint was ICU mortality.A total of 271 patients were included. SRD included systemic lupus erythematosus (23.2% of included patients), vasculitis (10.7%), systemic sclerosis (10.7%), idiopathic inflammatory myopathy (6.3%), and other connective tissue disorders (rheumatoid arthritis, Sjögren and Sharp syndromes; 50.9%). Initial organ failure(s) were shock (43.5% of included patients), acute kidney injury (30.5%), and acute respiratory failure (23.2%). The cause(s) of ICU admission included sepsis (61.6%), cardiovascular events (33.9%), SRD-flare up (32.8%), and decompensations related to comorbidities (28%). The ICU mortality reached 14.3%. The factors associated with ICU mortality were chronic cardiac failure, invasive ventilation and admission in ICU for another reason than sepsis or SRD flare-up. The median follow-up after ICU discharge was 33.6 months. During follow-up, 109 patients died. The factors associated with long-term mortality included age, Charlson comorbidity index, and ICU admission for sepsis or SRD flare-up.The ICU mortality of patients with SRD was low. Sepsis was the first cause of admission. Cardiovascular events and comorbidities negatively impacted ICU mortality. Admission for sepsis or SRD flare-up exerted a negative effect on the long-term outcome.

Risk factors associated with day-30 mortality in patients over 60 years old admitted in ICU for severe COVID-19: the Senior-COVID-Rea Multicentre Survey protocol.

INTRODUCTION: With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission. METHODS AND ANALYSIS: This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients' outcomes. ETHICS AND DISSEMINATION: The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04422340.

Comparison of clinical outcomes and accuracy of electrode placement between robot-assisted and conventional deep brain stimulation of the subthalamic nucleus: a single-center study.

BACKGROUND: Several surgical methods are used for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD). This study aimed to compare clinical outcomes and electrode placement accuracy after robot-assisted (RAS) versus frame-based stereotactic (FSS) STN DBS in Parkinson's disease. METHODS: In this single-center open-label study, we prospectively collected data from 48 consecutive PD patients who underwent RAS (Neuromate®; n = 20) or FSS (n = 28) STN DBS with the same MRI-based STN targeting between October 2016 and December 2018 in the university neurological hospital of Lyon, France. Clinical variables were assessed before and 1 year after surgery. The number of electrode contacts within the STN was determined by merging post-operative CT and pre-operative MRI using Brainlab® GUIDE™XT software. RESULTS: One year after surgery, the improvement of motor manifestations (p = 0.18), motor complications (p = 0.80), and quality of life (p= 0.30) and the reduction of dopaminergic treatment (p = 0.94) and the rate of complications (p = 0.99) were similar in the two groups. Surgery duration was longer in the RAS group (p = 0.0001). There was no difference in the number of electrode contacts within the STN. CONCLUSION: This study demonstrates that RAS and FSS STN DBS for PD provide similar clinical outcomes and accuracy of electrode placement.

Hemodynamic Response to Treatment and Outcomes in Pulmonary Hypertension Associated With Interstitial Lung Disease Versus Pulmonary Arterial Hypertension in Systemic Sclerosis: Data From a Study Identifying Prognostic Factors in Pulmonary Hypertension Associated With Interstitial Lung Disease.

OBJECTIVE: Patients with systemic sclerosis and both pulmonary hypertension and interstitial lung disease (SSc-PH-ILD) generally carry a worse prognosis than patients with SSc and pulmonary arterial hypertension (SSc-PAH) without ILD. There is no evidence of the efficacy of PAH therapies in SSc-PH-ILD. We undertook this study to compare survival of and response to treatment in patients with SSc-PH-ILD and those with SSc-PAH. METHODS: We analyzed 128 patients (66 with SSc-PH-ILD and 62 with SSc-PAH) from 15 centers, in whom PH was diagnosed by right-sided heart catheterization; they were prospectively included in the PH registry. All patients received PAH-specific therapy. Computed tomography of the chest was used to confirm or exclude ILD. RESULTS: At baseline, patients with SSc-PH-ILD had less severe hemodynamic impairment than those with SSc-PAH (pulmonary vascular resistance 5.7 Wood units versus 8.7 Wood units; P = 0.0005) and lower diffusing capacity for carbon monoxide (median 25% [interquartile range (IQR) 18%, 35%] versus 40% [IQR 31%, 51%]; P = 0.0005). Additionally, patients with SSc-PH-ILD had increased mortality (8.1% at 1 year, 21.2% at 2 years, and 41.5% at 3 years) compared to those with SSc-PAH (4.1%, 8.7%, and 21.4%, respectively; P = 0.04). Upon treatment with PAH-targeted therapy, no improvement in the 6-minute walk distance was observed in either group. Improvement in the World Health Organization functional class was observed less frequently in patients with SSc-ILD-PH compared to those with SSc-PAH (13.6% versus 33.3%; P = 0.02). Hemodynamics improved similarly in both groups. CONCLUSION: ILD confers a worse prognosis to SSc-PH. Response to PAH-specific therapy is clinically poor in SSc-PH-ILD but was not found to be hemodynamically different from the response observed in SSc-PAH.

Patients with acute heart failure treated with the CARRESS-HF diuretic protocol in association with canrenoate potassium: Tolerance of high doses of canrenoate potassium.

BACKGROUND: Oral mineralocorticoid receptor antagonists have failed to prove their efficacy for decongestion and potassium homeostasis in acute heart failure. Intravenous mineralocorticoid receptor antagonists have yet to be studied. AIM: The aim of this study was to confirm the safety of high-dose potassium canrenoate in association with classic diuretics in acute heart failure. METHODS: This retrospective single-centre study included consecutive patients who were hospitalized with acute heart failure between 2013 and 2018. One hundred patients with overload treated with the standardized diuretic protocol from the CARRESS-HF trial were included. There were no exclusion criteria relating to creatinine or kalaemia at the time of admission. Two groups were constituted on the basis of potassium canrenoate posology: a low-dose group (<300mg/day) and a high-dose group (≥300mg/day); the groups were similar in terms of baseline characteristics. RESULTS: Mean daily potassium canrenoate doses were 198mg/day (range 100-280mg/day) in the low-dose group and 360mg/day (range 300-600mg/day) in the high-dose group. There was no significant difference between the high-dose and low-dose groups in terms of mortality, dialysis, renal function, hyperkalaemia, haemorrhage, sepsis or confusion. CONCLUSIONS: Potassium canrenoate at high doses can be used safely in association with standard diuretics in acute heart failure, even in patients with altered renal function. A prospective study is required to evaluate the efficacy of high-dose potassium canrenoate in preventing hypokalaemia and improving decongestion.

Association of characteristics of tampon use with menstrual toxic shock syndrome in France.

BACKGROUND: Menstrual tampons are widely used in western countries. Indirect evidence suggests that tampon misuse could be associated with an increased risk of menstrual toxic shock syndrome (MTSS). The aim of this study was to determine what characteristics of tampon use are associated with increased risk of menstrual toxic shock syndrome (MTSS). METHODS: A nationwide, case-control study in France, was conducted with women that use tampons with MTSS diagnoses according to the CDC diagnostic criteria (n = 55, from January 2011, to December 2017) and a control group of women with no MTSS history (n = 126, from February to December 2017). Information regarding tampon use during a 6-month period was collected. Associations between tampon use and MTSS were assessed using logistic regression models stratified by residential area. FINDINGS: Compared to controls, women diagnosed with MTSS more frequently reported maximum tampon wear of >6 h (62% vs. 41%; P = 0.02), overnight tampon use (77% vs. 54%; P = 0.006), and neither read nor followed tampon instructions in case of reading (65% vs. 42%; P = 0.006). In univariate analysis, MTSS risk was two-fold higher with tampon use for >6 consecutive hours (odds ratio, 2.3 [95% CI, 1.2-4.5]), and three-fold higher with tampon use during sleep for >8 h (odds ratio, 3.2 [95% CI, 1.4-7.7]). In multivariate logistic regression analysis, only maximum tampon use for >6 h (odds ratio, 2.03 [95% CI, 1.04-3.98]), and neither read nor followed the tampon instructions in case of reading (odds ratio, 2.25 [95% CI, 1.15-4.39]) were independently associated with MTSS. INTERPRETATION: Our study suggests that the risk of MTSS was associated with using tampons for more than 6 h, overnight tampon use during sleep, and neither read nor followed tampon insertion instructions in case of reading. FUNDING: LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon within the programme "Investissements d'Avenir" (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR).

Symptoms of anxiety and depression in relatives after decisions of withholding and withdrawing life-sustaining treatments in emergency departments.

OBJECTIVE: The aim of our study was to assess anxiety and depression in patients' relatives after a decision of withholding and withdrawing life-sustaining treatments. METHODS: We conducted a prospective observational multicenter study in three university hospitals' emergency departments. The Hospital Anxiety and Depression Scale (HADS) was assessed on the relatives of patients admitted in emergency departments 3 days and 21 days after the decision of withholding or withdrawing life-sustaining treatments. RESULTS: Among the 109 patients with a decision of withholding or withdrawing life-sustaining treatments, 88 relatives were included and 74 (67, 8%) completed the 21-day follow up. Among those, 14 (18.9%) and 13 (17.6%) displayed symptoms of anxiety and depression at 3 days, respectively. After 21 days, symptoms anxiety and depression were still present in the same way for nine (12.2%) of the relatives. The median total HADS score was 13.5 [interquartile range (IQR): 8-16] at 3 days and 10 [IQR: 5-17] at 21 days. The symptoms of depression at 21 days were more frequent for the relatives of patients who died at 21 days (P = 0.03). CONCLUSION: We found symptoms of anxiety and depression in relatives after decisions of withholding and withdrawing life-sustaining treatments in emergency departments, which persist at 21 days. Further studies are needed to support these results and to search the relatives at risk to develop these symptoms.

Gabapentin and Memantine for Treatment of Acquired Pendular Nystagmus: Effects on Visual Outcomes.

BACKGROUND: The most common causes of acquired pendular nystagmus (APN) are multiple sclerosis (MS) and oculopalatal tremor (OPT), both of which result in poor visual quality of life. The objective of our study was to evaluate the effects of memantine and gabapentin treatments on visual function. We also sought to correlate visual outcomes with ocular motor measures and to describe the side effects of our treatments. METHODS: This study was single-center cross-over trial. A total of 16 patients with chronic pendular nystagmus, 10 with MS and 6 with OPT were enrolled. Visual acuity (in logarithm of the minimum angle of resolution [LogMAR]), oscillopsia amplitude and direction, eye movement recordings, and visual function questionnaires (25-Item National Eye Institute Visual Functioning Questionnaire [NEI-VFQ-25]) were performed before and during the treatments (gabapentin: 300 mg 4 times a day and memantine: 10 mg 4 times a day). RESULTS: A total of 29 eyes with nystagmus were evaluated. Median near monocular visual acuity improved in both treatment arms, by 0.18 LogMAR on memantine and 0.12 LogMAR on gabapentin. Distance oscillopsia improved on memantine and on gabapentin. Median near oscillopsia did not significantly change on memantine or gabapentin. Significant improvement in ocular motor parameters was observed on both treatments. Because of side effects, 18.8% of patients discontinued memantine treatment-one of them for a serious adverse event. Only 6.7% of patients discontinued gabapentin. Baseline near oscillopsia was greater among those with higher nystagmus amplitude and velocity. CONCLUSIONS: This study demonstrated that both memantine and gabapentin reduce APN, improving functional visual outcomes. Gabapentin showed a better tolerability, suggesting that this agent should be used as a first-line agent for APN. Data from our investigation emphasize the importance of visual functional outcome evaluations in clinical trials for APN.

Clostridium difficile: A Frequent Infection in Children After Intestinal Transplantation.

BACKGROUND: Organ transplantation (Tx) is a risk factor for Clostridium difficile infection (CDI). After intestinal transplantation (ITx), few data are available on the impact of this graft infection and the possible induction of rejection. METHODS: We included retrospectively all children after ITx in our unit, with at least 1 year of graft survival. All samples positive for Clostridium difficile (CD) and its toxin were considered. RESULTS: Among the 57 ITx recipients (60 Txs), 22 children (39%) developed culture-proven CDI, 12 after isolated small bowel Tx, 9 after liver-small bowel Tx, and 1 after multivisceral Tx. Twenty patients had diarrhea, 8 bloody stools, 4 fever, and 1 hypothermia. Nine were hospitalized for an average of 6.5 days (2-20) and 4 with severe dehydration. Nine (40%) had received antibiotics for an average of 19 days (7-60) before CDI. Two patients were asymptomatic. CDI was treated with metronidazole in 12 children, vancomycin in 6, and both in 3. Three children presented mild-to-severe rejections. Two patients presented concomitantly CDI and rejection. The third patient presented a rejection with severe complications 4 years after CDI. Recurrence of toxinogenic CD was observed in 9 children, in 7 associated with clinical symptoms. During the last follow-up, the stool number was the same as before CDI except for 1 patient with ongoing infection. CONCLUSIONS: CDI is more prevalent in children after ITx compared with other organ Tx; it is most often symptomatic but mildly or moderately severe. Standard antibiotics efficiently control the symptoms. Induction of rejection is a rare event.

Poor Involvement of General Practitioners in Decisions of Withholding or Withdrawing Life-Sustaining Treatment in Emergency Departments.

BACKGROUND: Decisions of withholding or withdrawing life-sustaining treatment are frequent in emergency departments (ED) and patients are often unable to communicate their wishes concerning end of life desires. OBJECTIVE: To evaluate the participation of general practitioners (GPs) during the decision-making process of withholding or withdrawing life-sustaining treatments in ED. DESIGN: Prospective observational multicenter study. PATIENTS: We included patients for whom a decision of withdrawing or withholding life-sustaining treatments was made in ED. For each patient, we enrolled one general practitioner. MAIN MEASURES: GPs were interviewed about their perception of end of life patient's management and the communication with ED and families. KEY RESULTS: There were 109 potential patient participants. We obtained answers from 54 (49.5%) of the patient's associated GPs. Only 4 (7.4%) GPs were involved during the decision-making process of withholding or withdrawing life-sustaining treatments. Among GPs, 29 (53.7%) were contacted by family after the decision, most often to talk about their difficult experience with the decision. A majority (94%) believed their involvements in these decisions were important and 68% wished to "always" participate in end of life decisions despite the fact that they usually don't participate in these decisions. Finally, 66% of GPs believed that management of end of life in the emergency department was a failure and should be anticipated. CONCLUSIONS: GPs would like to be more involved and barriers to GP involvement need to be overcome. We do not have any outcome data to suggest that routine involvement of GPs in all end of life patients improves their outcomes. Moreover, it requires major system and process-based changes to involve all primary care physicians in ED decision-making. NIH TRIAL REGISTRY NUMBER: NCT02844972.

Age at start of using tobacco on the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium (INHANCE).

BACKGROUND: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk. METHODS: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models. RESULTS: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR<10 years vs. ≥30 years: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR<10 years vs. ≥30 years: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed. CONCLUSIONS: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.

Difficulty of the decision-making process in emergency departments for end-of-life patients.

BACKGROUND: In emergency departments, for some patients, death is preceded by a decision of withholding or withdrawing life-sustaining treatments. This concerns mainly patients over 80, with many comorbidities. The decision-making process of these decisions in emergency departments has not been extensively studied, especially for noncommunicating patients. AIM: The purpose of this study is to describe the decision-making process of withholding and withdrawing life-sustaining treatments in emergency departments for noncommunicating patients and the outcome of said patients. DESIGN: We conducted a prospective multicenter study in three emergency departments of university hospitals from September 2015 to January 2017. RESULTS: We included 109 patients in the study. Fifty-eight (53.2%) patients were coming from nursing homes and 52 (47.7%) patients had dementia. Decisions of withholding life-sustaining treatment concerned 93 patients (85.3%) and were more frequent when a surrogate decision maker was present 61 (65.6%) versus seven (43.8%) patients. The most relevant factors that lead to these decisions were previous functional limitation (71.6%) and age (69.7%). Decision was taken by two physicians for 80 patients (73.4%). The nursing staff and general practitioner were, respectively, involved in 31 (28.4%) and two (1.8%) patients. A majority of the patients had no advance directives (89.9%), and the relatives were implicated in the decision-making process for 96 patients (88.1%). Death in emergency departments occurred for 47 patients (43.1%), and after 21 days, 84 patients (77.1 %) died. CONCLUSION: There is little anticipation in end-of-life decisions. Discussion with patients concerning their end-of-life wishes and the writing of advance directives, especially for patients with chronic diseases, must be encouraged early.

Ziconotide for spinal cord injury-related pain.

BACKGROUND: Central neuropathic pain related to spinal cord injury is notoriously difficult to treat. So far most pharmacological and surgical options have shown but poor results. Recently ziconotide has been approved for use both neuropathic and non-neuropathic pain. In this cohort study, we assessed responder rate and long-term efficacy of intrathecal ziconotide in patients with pain related to spinal cord injury. METHODS: Patients presenting chronic neuropathic related to spinal cord lesions that was refractory to medical pain management were considered for inclusion. Those accepting were tested by lumbar puncture injection of ziconotide or continuous intrathecal infusion and if a significant decrease in pain scores (>40%) was noted they were implanted with a continuous infusion pump. They were then followed up for at least 1 year with constant assessment of the evolution of pain and side effects. RESULTS: Out of the 20 patients tested 14 had a decrease in pain scores of more than 40% but only 11 (55%) were implanted with permanent pumps due to side effects and patient choice. These were followed up on average for 3.59 years (±1.94) and in eight patients an above threshold decrease in pain scores was maintained. Overall in patients that responded to the test baseline VAS was 7.91 and 4.31 at last follow-up with an average dose of 7.2 µg of ziconotide per day. Six patients (30%) did not respond to any test and in three patients side effects precluded pump implantation. No significant long-term effects of the molecule were noted. CONCLUSION: This study shows response to intrathecal ziconotide test in 40% of the patients of a very specific population in whom other therapeutic options are not available. This data justifies the development further studies such as a long-term randomized controlled trial. SIGNIFICANCE: Intrathecal Ziconotide is a posible alternative for the treatment of pain in patients with spinal cord injury and below level neuropathic pain.