Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol.

One of the most important components of sepsis management is hemodynamic restoration. If the target mean arterial pressure (MAP) is not obtained, the first recommendation is for volume expansion, and the second is for norepinephrine (NE). We describe the methodology of a randomized multicenter trial aiming to assess the hypothesis that low-dose NE given early in adult patients with sepsis will provide better control of shock within 6 hours from therapy starting compared to standard care. This trial includes ICU septic patients in whom MAP decrease below 65 mmHg to be randomized into 2 groups: early NE-group versus standard care-group. The patient's attending clinician will determine how much volume expansion is necessary to meet the target of a MAP > 65 mm Hg. If this target not achieved, after at least 30 ml/kg and guided by the available indices of fluid responsiveness, NE will be used in a usual way. The latter must follow a consensual schedule elaborated by the investigating centers. Parameters to be taken at inclusion and at H6 are: lactates, cardiac ultrasound parameters (stroke volume (SV), cardiac output (CO), E/E' ratio), and P/F ratio. MAP and diuresis are recorded hourly. Our primary outcome is the shock control defined as a composite criterion (MAP > 65 mm Hg for 2 consecutive measurements and urinary output > 0.5 ml/kg/h for 2 consecutive hours) within 6 hours. Secondary outcomes: Decrease in serum lactate> 10% from baseline within 6 hours, the received fluid volume within 6 hours, variation of CO and E/E', and 28 days-Mortality. The study is ongoing and aims to include at least 100 patients per arm. This study is likely to contribute to support the indication of early initiation of NE with the aim to restrict fluid intake in septic patients. (ClinicalTrials.gov ID: NCT05836272).

The Ability of Critical Care Physicians to Identify Patient-Ventilator Asynchrony Using Waveform Analysis: A National Survey.

BACKGROUND: Improved patient-ventilator asynchrony (PVA) identification using waveform analysis by critical care physicians (CCPs) may improve patient outcomes. This study aimed to assess the ability of CCPs to identify different types of PVAs using waveform analysis as well as factors related to this ability. METHODS: We surveyed 12 university-affiliated medical ICUs (MICUs) in Tunisia. CCPs practicing in these MICUs were asked to visually identify 4 clinical cases, each corresponding to a different PVA. We collected the following characteristics regarding CCPs: scientific grade, years of experience, prior training in mechanical ventilation, prior exposure to waveform analysis, and the characteristics of the MICUs in which they practice. Respondents were categorized into 2 groups based on their ability to correctly identify PVAs (defined as the correct identification of at least 3 of the 4 PVA cases). Univariate analysis was performed to identify factors related to the correct identification of PVA. RESULTS: Among 136 included CCPs, 72 (52.9%) responded to the present survey. The respondents comprised 59 (81.9%) residents, and 13 (18.1%) senior physicians. Further, 50 (69.4%) respondents had attended prior training in mechanical ventilation. Moreover, 21 (29.2%) of the respondents could correctly identify PVAs. Double-triggering was the most frequently identified PVA type, 43 (59.7%), followed by auto-triggering, 36 (50%); premature cycling, 28 (38.9%); and ineffective efforts, 25 (34.7%). Univariate analysis indicated that senior physicians had a better ability to correctly identify PVAs than residents (7 [53.8%] vs 14 [23.7%], P = .044). CONCLUSIONS: The present study revealed a significant deficiency in the accurate visual identification of PVAs among CCPs in the MICUs. When compared to residents, senior physicians exhibited a notably superior aptitude for correctly recognizing PVAs.

IgA is the predominant isotype of anti-ß2 glycoprotein I in patients with COVID-19.

OBJECTIVE: The aim of this research was to determine the frequency of antiphospholipid antibodies (aPL) in patients with COVID-19. METHODS: The frequency and titers of anticardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI) were determined in sera of adult patients hospitalized with COVID-19. Immunoglobulin (Ig)G, IgA, IgM aCL, and aß2GPI were measured using enzyme-linked immunosorbent assay. RESULTS: Eighty-three patients were included in the study. The mean age of patients was 62 ± 13.9 years, ranging from 23 to 86 years. Stratification according to severity of infection divided patients in 2 groups: 45 patients with moderate infection and 38 patients with critical or severe infection. Out of the 83 patients suffering from COVID-19, aPL (aCL or aß2GPI) were detected in 24 patients (28.9%). IgG, IgA and IgM aß2GPI were positive in 2.4%, 16.9% and 8.4%, respectively. IgG, IgA and IgM aCL showed positivity in 7.2%, 0%, and 4.8%, respectively. The frequency of aPL was 36.8% in patients with critical/severe infection and 22.2% in patients with moderate infection. In critical/severe patients, the frequency of aß2GPI was significantly higher than aCL (34.2% vs 13.2%, P = .03) and aß2GPI-IgA were significantly more frequent than aß2GPI-IgG (21.1% vs 2.6%, P = .028). CONCLUSION: In this cross-sectional study, aPL and particularly aß2GPI-IgA were common in patients with COVID-19.

Epidemiology and burden of Severe Acute Respiratory Infections (SARI) in the aftermath of COVID-19 pandemic: A prospective sentinel surveillance study in a Tunisian Medical ICU, 2022/2023.

BACKGROUND: Severe Acute Respiratory Infections (SARI) caused by influenza and other respiratory viruses pose significant global health challenges, and the COVID-19 pandemic has further strained healthcare systems. As the focus shifts from the pandemic to other respiratory infections, assessing the epidemiology and burden of SARI is crucial for healthcare planning and resource allocation. Aim: to understand the impact of the post-pandemic period on the epidemiology of SARI cases, clinical outcomes, and healthcare resource utilization in Tunisia. METHODS: This is a prospective study conducted in a Tunisian MICU part of a national sentinel surveillance system, focusing on enhanced SARI surveillance. SARI cases from week 39/2022, 26 September to week 19/2023, 13 May were included, according to a standardized case definition. Samples were collected for virological RT-PCR testing, and an electronic system ensured standardized and accurate data collection. Descriptive statistics were performed to assess epidemiology, trends, and outcomes of SARI cases, and univariate/multivariate analyses to assess factors associated with mortality. RESULTS: Among 312 MICU patients, 164 SARI cases were identified during the study period. 64(39%) RT-PCR were returned positive for at least one pathogen, with influenza A and B strains accounting for 20.7% of cases at the early stages of the influenza season. The MICU experienced a significant peak in admissions during weeks 1-11/2023, leading to resource mobilization and the creation of a surge unit. SARI cases utilized 1664/3120 of the MICU-stay days and required 1157 mechanical ventilation days. The overall mortality rate among SARI cases was 22.6%. Age, non-COPD, and ARDS were identified as independent predictors of mortality. CONCLUSIONS: The present study identified a relatively high rate of SARI cases, with 39% positivity for at least one respiratory virus, with influenza A and B strains occurring predominantly during the early stages of the influenza season. The findings shed light on the considerable resource utilization and mortality associated with these infections, underscoring the urgency for proactive management and efficient resource allocation strategies.

Clinical Features and Outcomes of Acute Kidney Injury in Critically Ill COVID-19 Patients: A Retrospective Observational Study.

BACKGROUND: An alarming number of COVID-19 patients, especially in severe cases, have developed acute kidney injury (AKI). AIM: The study aimed to assess the frequency, risk factors, and impact of AKI on mortality in critically ill COVID-19 patients. METHODS: The study was a retrospective observational study conducted in the MICU. Univariate and multivariate analyses were performed to identify risk factors for AKI and clinical outcomes. RESULTS: During the study period, 465 consecutive COVID-19 patients were admitted to the MICU. The patients' characteristics were median age, 64 [54-71] years; median SAPSII, 31 [24-38]; and invasive mechanical ventilation (IMV), 244 (52.5%). The overall ICU mortality rate was 49%. Two hundred twenty-nine (49.2%) patients developed AKI. The factors independently associated with AKI were positive fluid balance (OR, 2.78; 95%CI [1.88-4.11]; p < 0.001), right heart failure (OR, 2.15; 95%CI [1.25-3.67]; p = 0.005), and IMV use (OR, 1.55; 95%CI [1.01-2.40]; p = 0.044). Among the AKI patients, multivariate analysis identified the following factors as independently associated with ICU mortality: age (OR, 1.05; 95%CI [1.02-1.09]; p = 0.012), IMV use (OR, 48.23; 95%CI [18.05-128.89]; p < 0.001), and septic shock (OR, 3.65; 95%CI [1.32-10.10]; p = 0.012). CONCLUSION: The present study revealed a high proportion of AKI among critically ill COVID-19 patients. This complication seems to be linked to a severe cardiopulmonary interaction and fluid balance management, thus accounting for a poor outcome.

Resource utilization and preparedness within the COVID-19 pandemic in Tunisian medical intensive care units: A nationwide retrospective multicentre observational study.

BACKGROUND: The worldwide SARS-CoV-2 pandemic represents the most recent global healthcare crisis. While all healthcare systems suffered facing the immense burden of critically-ill COVID-19 patients, the levels of preparedness and adaptability differed highly between countries. AIM: to describe resource mobilization throughout the COVID-19 waves in Tunisian University Medical Intensive Care Units (MICUs) and to identify discrepancies in preparedness between the provided and required resource. METHODS: This is a longitudinal retrospective multicentre observational study conducted between March 2020 and May 2022 analyzing data from eight University MICUs. Data were collected at baseline and at each bed expansion period in relation to the nation's four COVID-19 waves. Data collected included epidemiological, organizational and management trends and outcomes of COVID-19 and non-COVID-19 admissions. RESULTS: MICU-beds increased from 66 to a maximum of 117 beds. This was possible thanks to equipping pre-existing non-functional MICU beds (n = 20) and creating surge ICU-beds in medical wards (n = 24). MICU nurses increased from 53 to 200 of which 99 non-ICU nurses, by deployment from other departments and temporary recruitment. The nurse-to-MICU-bed ratio increased from 1:1 to around 1·8:1. Only 55% of beds were single rooms, 80% were equipped with ICU ventilators. These MICUs managed to admit a total of 3368 critically-ill patients (15% of hospital admissions). 33·2% of COVID-19-related intra-hospital deaths occurred within the MICUs. CONCLUSION: Despite a substantial increase in resource mobilization during the COVID-19 pandemic, the current study identified significant persisting discrepancies between supplied and required resource, at least partially explaining the poor overall prognosis of critically-ill COVID-19 patients.

Management of patients with cardiovascular diseases during Ramadan.

During the month of Ramadan, over one billion Muslims observe a water and food fast from sunrise to sunset. The practice of this religious duty causes marked changes in eating and sleeping habits. With the increasing incidence of cardiovascular (CV) risk factors, the number of patients with CV pathologies who wish to fast is increasing worldwide, and in Tunisia, which is ranked as a high CV risk country. If fasting has been shown to be beneficial for the improvement of some metabolic parameters, its practice in patients with CV pathology remains debated. The Tunisian Society of Cardiology and Cardiovascular Surgery (STCCCV) in consultation with the National Instance of Evaluation and Accreditation in Health (INEAS) has established this document in the form of a consensus after having analysed the literature with the aim of addressing these questions: -What is the impact of fasting in patients with CV pathologies? -How to stratify the risk of fasting according to CV pathology and comorbidities? -How to plan fasting in patients with CV diseases? -What are the hygienic and dietary measures to be recommended during fasting in patients with CV pathologies? -How to manage medication during the month of Ramadan in patients with CV diseases?

Stress, anxiety, and depression among students at the Faculty of Medicine of Sousse (Tunisia).

OBJECTIVE: To evaluate the frequency of anxious and depressive symptoms and to determine their associated factors in a population of students enrolled at the Faculty of Medicine of Sousse (Tunisia). METHODS: this is a descriptive cross-sectional study that took place at the Faculty of Medicine of Sousse over the period from 09/15/2017 to 03/15/2018. An anonymous questionnaire was administered to the students in the guided teaching rooms. The assessment of anxiety and depressive symptoms was based on the Anxiety and Depression Scale (HADS) and the quality of sleep was assessed by the PSQI questionnaire. RESULTS: A total of 202 medical students participated in the study. The average PSQI score was 5.62±2.87 and 47% of students had poor sleep quality (PSQI ≥ 6). Symptoms of anxiety and depression were observed in 73 (36.1%) and 45 (22.3%) students respectively. The mean HADS-A score was 9.21±4.17 and that of the HADS-D score was 7.37±4.06. In univariate analysis, the factors found to predict a high level of perceived stress were the study cycle (p=0.022) and poor quality of sleep (p 11) were the use of sleeping pills (p=0.004), the quality of sleep (p<0.001), and a high level of perceived stress (p<0.001). The high level of perceived stress was found to predict depression (p=0.006).In the multivariate analysis of variables in the present study, poor sleep quality was a factor independently related to high perceived stress in medical students (ORa=9.062 [4.247-19.334]) while being a medical student of the 1st cycle proved to be a protective factor (ORa=0.101 [0.025-0.406]). Use of sleeping pills (ORa=4.481 [1.135-17.682]), poor sleep quality (ORa=2.131 [1.081-4.203]) and high level of perceived stress (ORa=5.790 [2.444-13.716]) were factors independently related to anxiety symptoms. Female sex was a protective factor for depressive symptoms (ORa=0.440 [0.205-0.945]) while a high level of perceived stress was a factor independently related to depressive symptoms (ORa=3.429 [1.469-8.005]). HAD-A and HAD-D scores were correlated (r=0.631 ; p<0.001). CONCLUSION: sleep disturbances, perceived stress, anxious and depressive symptoms are common among Tunisian medical students. Prevention strategies targeting the improvement of sleep quality and student stress management should be developed at the faculty and ministerial level.

Acquired Thrombotic Thrombocytopenic Purpura Following Inactivated COVID-19 Vaccines: Two Case Reports and a Short Literature Review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in December 2019, causing millions of deaths all over the world, and the lack of specific treatment for severe forms of coronavirus disease 2019 (COVID-19) have led to the development of vaccines in record time, increasing the risk of vaccine safety issues. Recently, several cases of thrombotic thrombocytopenic purpura (TTP) have been reported following COVID-19 vaccination. TTP is a rare disease characterized by thrombocytopenia, microangiopathic hemolytic anemia and ischemic end-organ lesions. It can be either congenital or acquired. Various events such as viral infections, medication, pregnancy, malignancies, and vaccinations may cause TTP. Here, we report two cases of acquired TTP following Sinopharm COVID-19 vaccine (BBIBP-CorV) and Sinovac COVID-19 vaccine (CoronaVac). Diagnosis was based on clinical presentation and confirmed with a severe reduction in the activity of von Willebrand factor-cleaving protease ADAMTS-13 and the presence of inhibitory autoantibodies. The two patients were successfully treated with corticosteroids, plasma exchange therapy and rituximab in the acute phase. In the literature, the reported cases of TTP induced by COVID-19 vaccination occurred after Adenoviral Vector DNA- and SARS-CoV-2 mRNA-Based COVID-19 vaccines. To the best of our knowledge, this is the first report of acquired TTP after inactivated virus COVID-19 vaccination.

North-African doctors as second victims of medical errors: a cross sectional survey.

INTRODUCTION: Physicians involved in medical errors (MEs) can experience loss of self-esteem and negative psychological experiences. They are called "second victims" of the ME. AIMS: To i) describe the profile, the types and the severity of MEs, and ii) explore the psychological impact on "second victims" to better understand how they cope. METHODS: It was a cross sectional retrospective study conducted from March to August 2018. All physicians working at Farhat Hached and Sahloul University hospitals were asked to complete a questionnaire about their possible MEs. The impact of MEs was evaluated using the Impact of Event Scale-Revised (IES-R) (scoring, 0-88) (subscales ranges; intrusion, (0-32); avoidance, (0-32); hyperarousal, (0-24)). The diagnosis of post-traumatic stress disorder (PTSD) was made when the total IES-R score exceeded 33. The coping strategies were evaluated using Ways of Coping Checklist Revised (WCC-R) scale (scoring, problem-focused, (10-40); emotion focused, (9-36); seeking social support, (8-32)). RESULTS: Among 393 responders, 268(68.2%) reported MEs. Wrong diagnosis (40.5%), faulty treatment (34.6%), preventive errors (13.5%) and faulty communication (6.4%) were the main frequent types of MEs. The most common related causes of MEs were inexperience (47.3%) and job overload (40.2%). The physicians' median (range) score of the IES-R was 19(0-69). According to the IES-R score, the most frequent psychological impacts were median (range): intrusion, 7(0-28) and avoidance symptoms, 7(0-24). PTSD symptoms affected 23.5% of physicians. Female sex and serious MEs were identified as predictors of PTSD. On the WCC-R check list, coping was balanced between the three coping strategies median (range), problem focused, 28.5(10-40); emotion-focused, 24(9-36) and seeking social support 21(8-32). CONCLUSION: There is a relatively high impact of ME within these North-African university hospital physicians. Coping was balanced within different three strategies as reported worldwide. Physicians adopted more likely constructive changes than defensive ones.

Very severe COVID-19 in the critically ill in Tunisia.

INTRODUCTION: SARS-CoV-2 is an emerging health threat outbreak. It may cause severe viral pneumonia with Acute Respiratory Distress Syndrome requiring critical care. Aim: to describe clinical features and outcomes of critically ill patients with SARS-CoV-2 infection. METHODS: it was a retrospective study carried out in the medical ICU of Farhat Hached teaching hospital between March 11 and May 7, 2020. All consecutive patients with RT-PCR confirmed COVID-19 were included. Clinical characteristics and outcomes were collected by reviewing medical records. RESULTS: during the study period, 10 critically ill patients with COVID-19 were enrolled. Mean age, 51.8±6.3 years; 8(80%), male. The most common comorbidities were; diabetes mellitus, 6(60%), obesity 2(20%), chronic kidney disease 2(20%) and hypertension 1(10%). Mean SAPS II, 23.2±1.8. The mean arterial oxygen partial pressure to fractional inspired oxygen ratio at admission was 136.2±79.7. Noninvasive mechanical ventilation was used in 4(40%) patients and 7(70%) received invasive mechanical ventilation. Tidal volume and PEEP were set respectively within the median [IQR] of, 5.7[5.6-6.3]ml/Kg and 10.7[6.5-11.7]cm H2O. Plateau pressure was monitored in the median [IQR] of 27.9 [25.9-28.5] cm H2O. Four patients received hydroxychloroquine alone and five hydroxychloroquine associated with an antiviral. Five patients developed respectively hyperactive (n=2), hypoactive (n=2) and mixed delirium (n=1). Mortality rate was at 70%. CONCLUSION: this study demonstrated a particular profile of COVID-19 in the critically ill as a severe presentation in aged males with comorbidities presenting with an ARDS-like and neurological impairment with poor prognosis. The only survivals seem to have benefited from noninvasive ventilatory support.

Artery of Percheron Stroke as an Unusual Cause of Hypersomnia: A Case Series and a Short Literature Review.

The thalamus and the mesencephalon have a complex blood supply. The artery of Percheron (AOP) is a rare anatomical variant. Occlusion of this artery may lead to bithalamic stroke with or without midbrain involvement. Given its broad spectrum of clinical features, AOP stroke is often misdiagnosed. Usually, it manifests with the triad of vertical gaze palsy, memory impairment, and coma. In this article, we report three cases of bilateral thalamic strokes whose clinical presentations were dominated by a sudden onset of hypersomnia. We also reviewed last 5 years' publications related to the AOP strokes in males presenting sleepiness or equivalent terms as a delayed complication. The AOP stroke may present a diagnostic challenge for clinicians which should be considered in the differential diagnosis of hypersomnia.