[COVID-19 Pandemic: Psychosocial impact among healthcare professionals in Tunisia]. / Pandémie COVID-19 : impact psychosocial sur le personnel de santé en Tunisie.

OBJECTIVE: To determine the psycho-affective impact of the Covid-19 pandemic on the mental health of health professionals in Tunisia and to estimate the associated factors. METHODS: This is a multicenter, cross-sectional, descriptive and analytical study of health professionals carried out from May 2, 2020 to June 30, 2020 in Tunisia. Healthcare professionals included doctors, nurses, dentists and pharmacists. The participants answered a pre-established questionnaire using an electronic "Google Form". This questionnaire gathered demographic data and medical history. It included two psychometric scales, the GAD-7 (General Anxiety Disorder-7) and the PHQ-9 (Patient Health Questionnaire-9) to assess the prevalence and intensity of anxiety symptoms and depressive symptoms respectively. RESULTS: The study included 203 healthcare professionals. The professionals had a mean age of 30.74±6.33years, 69.5 % were women, and the majority were doctors (77.8 %). Among professionals, 9.4 % were nurses, 7.4 % were dentists, and 5.4 % were pharmacists. A third of the participants 34.3 % worked in departments with Covid-19 patienfor having moderate to severe anxiety symptoms. CONCLUSION: In order to ensure better patient care, early detection of psychiatric disorders and the implementation of specific strategies to ensure better mental health among healthcare professionals are priorities not only during the current pandemic but also in the event of a future similar pandemic.

Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplastic syndrome.

Posaconazole is a broad-spectrum triazole antifungal available as an oral suspension. Pharmacokinetic data showed a high variability of plasma posaconazole concentrations (PPCs) in patients, suggesting a potential interest in drug monitoring. The aim of our prospective study was to measure the PPCs in prophylactically treated patients to evaluate the impact of different factors on these concentrations. In 40 patients treated prophylactically with posaconazole for acute myeloid leukemia or myelodysplastic syndrome between February 2009 and August 2010, PPCs were measured at day 7 of treatment and then twice weekly. Demographic data, clinical data (including gastrointestinal disorders, comedications, and treatment compliance), caloric and fat intake, and biological data were collected and evaluated. We obtained 275 measurements of PPCs, with a median of 430 ng/ml. PPCs were significantly lower in patients with mucositis (P < 0.001), nausea (P = 0.03), diarrhea (P = 0.03), or vomiting (P = 0.05). PPCs were higher in patients with a higher caloric intake (P = 0.02), while the proportion of fat intake had no influence on PPCs (P = 0.84). The concomitant use of proton pump inhibitors decreased the PPCs (P = 0.02), while the use of tacrolimus increased the PPC (P = 0.03). In the multivariate analysis, the factors influencing the PPCs independently were the concomitant use of tacrolimus (P < 0.001), the presence of mucositis (P = 0.01), and food intake (P = 0.02). Our study confirmed the high variability of posaconazole bioavailability and showed the significant influence of gastrointestinal disorders, food intake, and concomitant medication on the PPCs. However, the optimal PPCs still remain to be defined and correlated with clinical efficacy.

M-ficolin levels are associated with the occurrence of severe infections in patients with haematological cancer undergoing chemotherapy.

The pattern recognition molecules H-ficolin, L-ficolin and M-ficolin bind to micro-organisms. They activate the lectin pathway of complement through mannan-binding lectin (MBL)-associated serine proteases (MASPs). Association between low MBL levels and infections in patients undergoing chemotherapy for haematological diseases has been observed previously. We now examine for MASP-2, MASP-3 and ficolin levels. We assessed the concentration of lectin pathway molecules as risk factors for infection in patients with haematological malignancy undergoing chemotherapy. Samples taken before the initiation of chemotherapy covering 117 chemotherapy cycles in 105 patients were available. MASPs and ficolins were measured by time-resolved immunoflourometric assays and the levels related to parameters of infections. End-points included febrile neutropenia, documented infections, bacteraemia or severe infections. Lower M-ficolin concentrations were found in patients who developed a severe infection: median 0·27 µg/ml compared to 0·47 µg/ml in patients who did not develop a severe infection (P = 0·01). Conversely, MASP-2 was higher in these patients: median 0·53 µg/ml compared to 0·37 µg/ml, respectively (P = 0·008). When considering M-ficolin levels below 0·36 µg/ml as deficient, the time to development of severe infection was shorter in the M-ficolin deficient group: the hazard ratio was 2·60 (95% confidence interval: 1·23-5·49). No associations were revealed between infections and H-ficolin, L-ficolin or MASP-3. Patients with low M-ficolin are more likely to develop severe infections, whereas MASP-2 showed the opposite.

An observational efficacy and safety analysis of the treatment of acute invasive aspergillosis using voriconazole.

The purpose of this study was to evaluate efficacy and safety of voriconazole in patients with acute invasive aspergillosis (IA) in a real-life, clinical setting. This was a multicenter observational study in adult patients treated with voriconazole for invasive mycosis. The study evaluated clinical response, mortality, use of other licensed antifungal therapy (OLAT), and treatment duration. This sub-analysis evaluated treatment and outcome data specifically from adult patients with proven/probable IA, while safety data were assessed in patients with proven/probable/possible IA. Of the 141 patients enrolled, 113 were adults with proven/probable IA and six had possible IA. Voriconazole treatment duration ranged from 1 to 183 days (median, 49.5 days). Voriconazole was used exclusively in 64% (72/113) of patients and in combination/sequentially with OLAT in 36%. Overall successful treatment response was 50% (57/113 patients). Twelve percent (14/113) of patients were switched to OLAT, either because of insufficient response (four patients) or for safety reasons (10 patients). Overall and attributable (entirely or partially due to fungal infection) mortality rates were 52% (59/113) and 17%, respectively. Treatment-related adverse events were reported for 18% (22/119) of patients. This observational study confirms the results of previous clinical trials demonstrating voriconazole as an effective and safe agent for treatment of confirmed acute IA.

Releases of phosphate fertilizer industry in the surrounding environment: investigation on heavy metals and polonium-210 in soil.

Distribution of Cu, Zn, Pb, Cr, Ni, Mn concentrations and the activity of polonium-210 in the surrounding area of a phosphate fertilizer industry located on the eastern coast of the Mediterranean Sea has been determined. Nineteen sampling sites were distributed around the industrial zone on a surface area of about 100,000 m2. Atomic absorption spectroscopy and Alpha spectroscopy were used to quantify the heavy elements and polonium-210, respectively. Investigation on a particle scale was conducted by TEM and SEM coupled to EDX and X-ray cartography to determine the nature of heavy elements carriers and their distribution. Heavy elements were mainly concentrated inside the particle size fraction < 50 microm. Their levels decreased with distance increasing from the industry. According to the reference soil, enrichment factors were about 10, 15, 32 and 100 times for Zn, Pb, Cu, and Cr, respectively inside the particle size fraction < 50 microm on the closest sites to the industry. The main contaminant sources were transport and storage of row materials and the free release of phosphogypsum waste. Heavy elements were entrapped inside agglomerates of sulfates, phosphates and iron oxihydroxides in a diffused shape. Polonium-210 with an enrichment factor of about 56, showed the same behavior of the spatial distribution of the trace elements.

[Incidence and risk factors of depression after a first coronary acute syndrome: A prospective study among 110 patients]. / Incidence et facteurs de risque de la dépression post syndrome coronarien aigu : étude prospective auprès de 110 patients.

AIM: The purpose of this study was to estimate the incidence of post-acute coronary syndrome (ACS) depression and to identify predictive factors for the onset of this disorder. PATIENTS AND METHODS: We conducted a prospective, multicentric study across four cardiology departments, during the period from June to December 2018. A depressive symptom screening was performed using the Hospital Anxiety and Depression Scale, in-hospital (T0) and on average 42.1±7.9 days after hospital discharge (T1). RESULTS: A total of 110 patients were enrolled with an average age of 57±8.1 years. Sex ratio was 3.78. The incidences of depressive symptomatology at T0 and T1 were respectively 19.1% and 6.2%. Mean and cumulative incidences of depressive symptomatology were respectively 12.7% and 25.5%. According to the univariate analysis, drinking alcohol, overweight and anxiety were associated with the incidence of depressive symptomatology after SCA at T0. In binary logistic regression, drinking alcohol was the independent predictor of the incidence of depression after ACS at T0 with an odds ratio of 4.680 and CI of 95% [1.449; 15,107]; P=0.01. In univariate analysis, drinking alcohol, high risk of hospital mortality, according to the GRACE score, and non performing coronary angiography were statistically associated with the overall incidence of depressive symptomatology. CONCLUSION: Depression screening must be a part of the evaluation of the ACS. A repeated evaluation of depression is also recommended.

A general chemotherapy myelotoxicity score to predict febrile neutropenia in hematological malignancies.

BACKGROUND: Chemotherapy-induced neutropenia is the most common adverse effect of chemotherapy and is often complicated by febrile neutropenia (FN). The objective of this study is to validate a classification of aggressiveness of a chemotherapy regimen and to evaluate its usefulness in a risk prediction model of FN in patients with hematological cancer at the beginning of a chemotherapy cycle. PATIENTS AND METHODS: Two hundred and sixty-six patients were prospectively enrolled and followed during 1053 cycles. Relevant patient informations were collected at the beginning of the first cycle and the number of days of FN were counted in the follow-up [dichotomized (no FN versus >or= 1 day of FN)]. RESULTS: Aggressive chemotherapy regimen is the major predictor of FN [odds ratio 5.2 (3.2-8.4)]. The other independent predictors are the underlying disease, an involvement of bone marrow, body surface

Non-Hodgkin's lymphoma and tuberculosis coexistence in the same organs: a report of two cases.

Non-Hodgkin's lymphoma (NHL) may be preceded by chronic inflammatory diseases and furthermore has been related to immune deficiency. Tuberculosis (TB), on the other hand, is a chronic infectious disease whose presentation and reactivation is known to be promoted by cell mediated immunodeficiency. The coexistence of NHL and TB in the same organ is rare. We report two cases of NHL and TB coexistence in two different organs: cervical lymph nodes and kidney. The cases illustrate how misleading the concurrence of NHL and TB infection can be, delaying the diagnosis and treatment of either disease.

Low mannose-binding lectin concentration is associated with severe infection in patients with hematological cancer who are undergoing chemotherapy.

BACKGROUND: Mannose-binding lectin (MBL) is a serum lectin involved in innate immune response. Low serum MBL concentration may constitute a risk factor for infection in patients receiving myelosuppressive chemotherapy. METHODS: We conducted a prospective, observational study that assessed MBL concentration as a risk factor for infection in patients with hematological malignancy who were hospitalized to undergo at least 1 chemotherapy cycle. MBL deficiency was defined using an algorithm that considered the serum MBL concentration and the MBL genotype. The primary end point was the ratio of duration of febrile neutropenia to the duration of neutropenia. Secondary end points included the incidence of severe infection (e.g., sepsis, pneumonia, bacteremia, and invasive fungal infection). Logistic regression analysis was conducted, and Fisher's exact test was used to analyze binary outcomes, and Kaplan-Meier estimates and log rank tests were used for time-to-event variables. RESULTS: We analyzed 255 patients who received 569 cycles of chemotherapy. The median duration of neutropenia per cycle was 7 days (interquartile range, 0-13 days). Sixty-two patients (24%) were found to have MBL deficiency. Febrile neutropenia occurred at least once in 200 patients. No difference in the primary outcome was seen. The incidence of severe infection was higher among MBL-deficient patients than among non-MBL-deficient patients (1.96 vs. 1.34 cases per 100 days for analysis of all patients [P=.008] and 1.85 vs. 0.94 cases per 100 days excluding patients with acute leukemia [P<.001]). CONCLUSIONS: MBL deficiency does not predispose adults with hematological cancer to more-frequent or more-prolonged febrile episodes during myelosuppressive chemotherapy, but MBL-deficient patients have a greater number of severe infections and experience their first severe infection earlier, compared with nondeficient patients.

Bacteraemia in febrile neutropenic cancer patients.

A total of 2142 patients with febrile neutropenia resulting from cancer chemotherapy were registered in two observational studies and followed prospectively in different institutions. There were 499 (23%) patients with bacteraemia who are reviewed here. The relative frequencies of Gram-positive, Gram-negative and polymicrobial bacteraemias were 57%, 34% and 10% with respective mortality rates of 5%, 18% and 13%. Mortality rates were significantly higher in bacteraemic patients than in non-bacteraemic patients; a trend for higher mortality was observed (without reaching statistical significance) in those patients in whom bacteraemia was associated with a clinical site of infection compared to bacteraemic patients without any clinical documentation. Prophylactic antibiotics but not granulopoiesis stimulating factors were associated with a lower incidence of Gram-negative bacteraemia; however, neither prophylactic approach influenced the subsequent rate of complications in the patients who developed bacteraemia. The present study also confirms that the MASCC scoring system can identify a group of bacteraemic patients with a relatively low risk of complications and death (MASCC >/=21). On the other hand, in patients with very low levels of the MASCC score (<15), and then with predicted very unfavourable risk, the rate of complications and death was dramatically high, irrespective of the microbiological nature of the bacteraemia.

Model-free adaptive fractional order control of stable linear time-varying systems.

This paper presents a new model-free adaptive fractional order control approach for linear time-varying systems. An online algorithm is proposed to determine some frequency characteristics using a selective filtering and to design a fractional PID controller based on the numerical optimization of the frequency-domain criterion. When the system parameters are time-varying, the controller is updated to keep the same desired performances. The main advantage of the proposed approach is that the controller design depends only on the measured input and output signals of the process. The effectiveness of the proposed method is assessed through a numerical example.

Public exposure to radioactivity levels in the Lebanese environment.

In the framework of a National Environmental Radiation Survey Program, a total of 950 samples were collected and analyzed over 7 years. The program covers different compartment of Lebanese environment, rivers, wells, marine samples, soil, and foodstuff. Air was monitored continuously through a radiation early warning network system. Data collected from 2009 to 2015 are presented in this work. Gross alpha/gross beta values in well samples were below the guidance levels stated by the WHO. Cesium-137 was detected in milk samples, whey, and jam. However, its content was much lower than the national permissible level, while its activity concentration in marine samples was lower than the values reported in studies carried out in the Mediterranean Sea. The activity concentration of 40K in food samples was comparable to studies carried out in neighboring countries and higher than the content determined in non Mediterranean countries. Concerning marine environment, the activity concentrations of natural radionuclides 238U, 232Th, and 40K were comparable to those reported in other studies carried out in different countries. As well as their content in rivers and sediments was lower than those reported in neighboring region. Potassium-40 in food and 210Po in fish were the main contributors to the internal dose. The average annual effective dose due to external exposure and internal, excluding radon gas which constitutes around 43 % of the total dose, was found to be lower than the total worldwide value, 2.4 mSv year-1. Iodine-131 was detected in grass samples, collected in 2011 during Fukushima accident; its content ranged from 0.40 ± 0.06 to 0.9 ± 0.1 Bq kg-1, as well as 137Cs was detected in some seafood samples imported from Japan and neighboring countries. Its activity concentration varied between 0.15 ± 0.04 and 0.40 ± 0.02 Bq kg-1.

Clinical efficacy of caspofungin in the treatment of invasive aspergillosis.

Caspofungin, the main representative of the echinocandin family has undergone a clinical experience that covers gradually the whole spectrum of the standard care of invasive aspergillosis (IA). Caspofungin salvage therapy in cases of previous therapy refractoriness or intolerance resulted in a 45% response rate. Empiric therapy with caspofungin compared with L-AMB in neutropenic patients with persisting fever showed an overall response rate of approximately 34%, with less toxicity for caspofungin. Combination therapy of caspofungin with other antifungal drugs has been studied mainly retrospectively in open non randomized trials and in one prospective non comparative small study showing an encouraging response rate of 55% as salvage combined treatment. The clinical experience with caspofungin as first-line therapy in IA is limited to 32 patients with an overall response rate of 56%. Caspofungin is well tolerated with very few histamine-release reactions and a good toxicity profile.

Fever of unknown origin in cancer patients.

Fever of unknown origin (FUO) remains a challenging clinical problem, namely in patients with cancer. In cancer patients, FUO may be due to the cancer itself, as it is the case of hematological malignancies; digestive tumors (colon cancer, liver metastases) are significantly associated with FUO and infection can be demonstrated in some cases. Prevention with G-CSF and empirical antimicrobial therapy are essential approaches for the management of FUO in cancer patients. New diagnostic approaches, such as PET imaging, should be further evaluated in cancer patients with FUO.

Assessment of committed effective dose due to the ingestion of (210)Po and (210)Pb in consumed Lebanese fish affected by a phosphate fertilizer plant.

Ingestion of radionuclides through seafood intake is a one of the sources contributing to the internal effective dose in the human organism. In order to evaluate the internal exposure and potential risks due to (210)Po and (210)Pb associated with fish consumption, these radionuclides were measured in commonly consumed fish species from a clean area and an area subjected to the impact of a Lebanese phosphate fertilizer plant. The highest concentration of (210)Pb was 98.7 Bq/kg fresh weight while (210)Po activity concentrations varied from 3.6 Bq/kg to 140 Bq/kg. A supplementary radiation exposure was detected; the highest committed effective dose due to (210)Po and (210)Pb was found to be 1110 µSv/y and 450 µSv/y, respectively. Moreover, the average mortality and morbidity risks due to the fish consuming were estimated.

Evaluation of pretransplant influenza vaccination in hematopoietic SCT: a randomized prospective study.

Pretransplant influenza vaccination of the donor or allogeneic hematopoietic SCT (HSCT) candidate was evaluated in a randomized study. One hundred and twenty-two HSCT recipients and their donors were assigned to three randomization groups: no pretransplant vaccination (n=38), donor pretransplant vaccination (n=44) or recipient pretransplant vaccination (n=40). Specific IgG was assessed by both hemagglutinin inhibition (HI) and, in 57 patients, by an indirect influenza-specific ELISA at specified times after HSCT. Vaccinated donors had seroprotective HI titers for Ags H1 and H3 (P<0.001) compared with the other groups at the time of donation. The titers against H1 (P=0.028) and H3 (P<0.001) were highest in the pretransplant recipient vaccination group until day 180 after transplantation. A significant difference was found in the specific Ig levels against pandemic H1N1 at 6 months after SCT (P=0.02). The mean IgG levels against pandemic H1N1 and generic H1N1 and H3N2 were highest in the pretransplant recipient vaccination group. We conclude that pretransplant recipient vaccination improved the influenza-specific seroprotection rates.

An open multicentre comparative study of the efficacy, safety and tolerance of fluconazole and itraconazole in the treatment of cancer patients with oropharyngeal candidiasis.

Oropharyngeal candidiasis is a frequent infection in cancer patients who receive cytotoxic drugs. In this study, the efficacy, safety and tolerance of fluconazole and itraconazole were compared in non-neutropenic cancer patients with oropharyngeal candidiasis. Of 279 patients who were randomised between the two treatment groups, 252 patients were considered to be eligible (126 in each group). The clinical cure rate was 74% for fluconazole and 62% for itraconazole (P=0.04, 95% Confidence Interval (CI): 0.5-23.3%). The mycological cure rate was 80% for fluconazole and 68% for itraconazole (P=0.03, 95% CI: 1.2-22.6%). The safety and tolerance profile of both drugs were comparable. This study has shown that in patients with cancer and oropharyngeal candidiasis, fluconazole has a significantly better clinical and mycological cure rate compared with itraconazole.

Drug treatment of pneumonia in the hospital. What are the choices?

Mortality and morbidity of nosocomial pneumonia remain high. Successful treatment of pulmonary infections depends on several factors including type of infection, offending pathogen, status of host defences, and adequate choice of antibiotic therapy. The physician's decision should aim at achieving antibiotic concentrations beyond the MIC at the site of infection. Gram-negative bacilli, notably Pseudomonos aeruginosa, Klebsiella pneumoniae and Escherichia coli, remain the most frequent agents in nosocomial pneumonia. Staphylococcus aureus and Streptococcus pneumoniae predominate among the Gram-positive cocci. Pneumocystis carinii predominates in immunocompromised patients. Protected sample bronchoscopy associated with quantitative cultures of samples, and quantification of intracellular microorganisms in cells recovered by broncho-alveolar lavage are two promising procedures which might replace previous, more aggressive methods. Penetration of antibiotics into lung tissue depends on physicochemical properties of the drug and the degree of inflammation of lung tissue. Quinolones, macrolides, tetracyclines and trimethoprim penetrate well into bronchial secretions. Penetration is moderate to low for aminoglycosides and beta-lactams. Fluoroquinolones and new beta-lactam agents, including third-generation cephalosporins imipenem, aztreonam and ticarcillin-clavulanate, showed comparative clinical efficacy in treatment of nosocomial pneumonia, with an efficacy rate close to 80%. Aminoglycosides should not be used alone. Combination therapy reduces but does not eliminate the risk of selection of Gram-negative resistant mutants. It should not be used routinely except for P. aeruginosa, Enterobacter cloacae and Serratia marcescens infections.

Bacteremia due to Stomatococcus mucilaginosus in neutropenic patients in the setting of a cancer institute.

This study reviews the clinical manifestations, causes and frequency of Stomatococcus mucilaginosus bacteremia in neutropenic cancer patients. We analyzed retrospectively all clinical and microbiological records of patients with S. mucilaginosus bacteremia. The incidence was compared with that of other pathogens causing bacteremia during neutropenia for the same period. S. mucilaginosus represented 5.9% of bacteremias in our neutropenic patients. Seven patients with hematologic malignancies and one with breast cancer are described. The common clinical presentation was one of sepsis. All patients presented with damaged mucosal barriers as the probable portal of entry, from either stomatitis or enterocolitis. All patients survived.