Clinical and biological assessment of lamotrigine and levetiracetam plasma assays at the Rennes University Hospital.

INTRODUCTION: Requests for lamotrigine and levetiracetam plasma assays have increased significantly since their development in the biological and forensic toxicology laboratory at the University Hospital of Rennes in 2015. The purpose of this study was to evaluate the follow-up of French National Authority for Health (HAS) guidelines for antiepileptic drug assays and the impact of assay results on medical management. METHODS: Two hundred and forty-two assay results of these two antiepileptics for 169 patients hospitalized in different care wards between 2015 and 2018 were retrospectively analyzed. RESULTS: The mean age of the study population was 50.3±25.4 years. Of the 207 assays prescribed for epilepsy, 177 (85.5%) were in line with the 2007 HAS guidelines, namely: 76/177 (42.9%) for therapeutic adjustment in the event of seizure recurrence or aggravation; 45/177 (25.4%) for specific clinical situations; 23/177 (13%) for proven or suspected poor compliance; 23/177 (13%) for suspected overdose; 8/177 (4.5%) following initiation of treatment; and 2/177 (1.1%) for drug interaction management. Thirty of the 207 assays (14.5%) were thus inappropriate. No significant differences were found regarding the hospitalization frequency after a visit to the emergency room (P=0.9) between patients with lamotrigine and/or levetiracetam plasma assays in therapeutic ranges versus those with concentrations outside the therapeutic ranges. Dosage changes were more frequent in patients with assays in therapeutic ranges compared to patients with plasma assays outside the therapeutic ranges (P=0.0015), suggesting a treatment reassessment primarily based on clinical criteria. CONCLUSION: The analysis of requests for antiepileptic drug assays at the University Hospital of Rennes revealed that clinicians were well aware of the HAS guidelines. In addition, the assay results were mainly consistent with clinical intuition, suggesting a real added value for patient management. However, the consequences in terms of changes in medical care seem limited. This assessment illustrates the importance of strengthening the dialogue between pharmacists, biologists and clinicians.

Liver morbidity due to Schistosoma mekongi in Cambodia after seven rounds of mass drug administration.

Severe liver disease due to Schistosoma mekongi was frequent in northern Cambodia. Between 1995 and 2002, seven rounds of mass chemotherapy (praziquantel) reduced infection from 50% to below 3%. In 2002, we assessed hepatosplenic morbidity by historical, clinical and ultrasonographic investigations in adults (older than 14 years) from endemic (n=342) and non-endemic (n=103) areas (Kratie province). Clinical hepatomegaly (25 vs. 0%), splenomegaly (55 vs. 0%), reported blood in stool (41 vs. 20%) and abdominal pain (78 vs. 57%) were significantly higher in the endemic area. In this area, significantly more subjects reported a family history of death due to schistosomiasis (12 vs. 0%); 63% (vs. 0%) reported having at least three treatments of praziquantel in previous years; and only 11% (vs. 99%) had normal liver ultrasonographic examination. Periportal fibrosis with portal hypertension was diagnosed in 46% (vs. 0%) of people in this area; 18% (vs. 0%) and 5% (vs. 0%) of portal hypertension was classified as moderate and severe, respectively. People aged between 24 and 35 years were mostly affected. There was no gender difference. The pathology in the endemic district is most probably residual morbidity of S. mekongi infections. Contributions of co-infections (hepatitis) cannot be excluded. Careful monitoring of the affected communities is required.

Effectiveness of various chemical disinfectants versus cleaning combined with heat disinfection on Pseudomonas biofilm in hemodialysis machines.

The development of bacterial biofilms in the hydraulic circuit of hemodialysis machines is routinely prevented by frequent use of a variety of chemical and heat disinfection strategies. This study compared the effectiveness of several chemical disinfectants, commonly used either alone or in combination with a treatment regimen that involved cleaning plus heat disinfection using an in vitro Pseudomonas biofilm model. Effectiveness of these procedures was evaluated using total and viable biomass quantitation and polysaccharide and endotoxin determination. The chemical disinfection procedures were only partially successful in removing all biofilm components. Heat disinfection alone killed viable biofilm bacteria, but did not remove all the biomass components, including endotoxin. The combination of cleaning with citric acid followed by heat disinfection was the most effective in eliminating all biofilm components from the hydraulic circuit of the in vitro model.

Value of bispectral index monitoring during cardiopulmonary resuscitation.

A 67-yr-old man, undergoing pulmonary metastasis resection, experienced a postoperative cardiopulmonary arrest as a result of severe bleeding. Cardiopulmonary resuscitation (CPR) was initiated, then bispectral index (BIS) monitoring was used which reassured the medical team of the adequacy of the resuscitation.

[Early perioperative mortality in a multidisciplinary hospital]. / Mortalité périopératoire précoce dans un hôpital pluridisciplinaire.

OBJECTIVE: To evaluate the incidence and the causes of early intra- and postoperative deaths in a multidisciplinary hospital. STUDY DESIGN: Retrospective survey. PATIENTS: All patients receiving an anaesthetic between 1992 and 1995. METHODS: Analysis of all deaths occurring during anaesthesia and in the subsequent 24 hours. Demographic data (age, gender) and medical data (ASA physical class, type of surgery and degree of emergency) were recorded. The contribution of anaesthesia, surgery or patient disease to fatal outcome was analysed. RESULTS: The analysis included 52,654 patients who underwent either general anaesthesia or epidural analgesia. Perioperative mortality (n = 170) was 1/310 patients (0.32%). The risk factors for mortality (multivariate analysis) were: age > 64 years (odds-ratio [OR] 4.8), ASA class > or = 3 (OR 16.6), emergency surgery (OR 3.6), duration of surgery > 115 minutes (OR 37.4). Fifty percent of deaths (95% confidence interval [CI] = 42-58) were related to patient's underlying diseases and 29% to surgery (CI 95% = 22-36). The percentage of deaths linked to anaesthesia was 17.6% (CI 95% = 11.9-23.3, 1/1,755), consisting of 8.2% (CI 95% = 4.1-9.3, 1/3,761) totally due to anaesthesia and 9.4% (CI 95% = 5-13.8, 1/3,291) only partially. The main aetiologies of the deaths linked to anaesthesia were a mismanagement of severe haemorrhages (30%), respiratory complications (23%) or cardiac complications (23%). The mismanagement of an intraoperative critical situation (46%) and a mistake in the post-operative care (33%) were the main causes. DISCUSSION: In this survey, mortality due to anaesthesia was higher than the rates reported in other studies. Human error remained the main cause.

Evidence of bacterial biofilm in tubing from hydraulic pathway of hemodialysis system.

Biofilms consist of microorganisms immobilized at a substratum surface embedded in an organic polymer matrix of bacterial origin. Tubing drawn from the fluid pathways within dialysis machines of various models were investigated for biofilm. Scanning electron microscopy (SEM), performed on approximately 2 cm2 samples of the tubing inner surfaces revealed that the inner surfaces of the tubing were covered with biofilms consisting of numerous deposits and glycocalix at different stages of formation with components containing bacteria and algae. Evaluations of biomass were performed from tubing sections of various lengths and inner diameters put in tubes containing water for injection and immersed in an ultrasound washtub for 1 h to ensure sloughing of the biofilm. Living bacteria were identified by plating on nutrient agar media and incubation for 48 h at 37 degrees C. Epifluorescent stains were used for the total bacteria count. Lipopolysaccharide levels were determined by the endotoxin activity measurements. Polyoside contents were determined by the colometric method, and the chemical oxygen demand was measured to evaluate the amount of organic substance. Biofilms detached from tubing samples drawn from the water path, bicarbonate path, and fresh dialysate path within dialysis machines contained approximately 1.10(3)-1.10(6) total bacteria/cm2, yet only some living bacteria were found. Endotoxin levels ranged from 1 to 12 EU/cm2. In contrast in the dialysate fluid, no bacteria were found, and the endotoxin content was under the detection level of the method. The polyoside content and chemical oxygen demand of the biomass ranged from 11 to 83 microg/cm2 and from 53 to 234 mg/cm2, respectively. It is concluded that a germ- and endotoxin-free dialysate does not exclude the risks and hazards of bacteria and endotoxin discharge from biofilm developed on the fluid pathway tubing, acting as a reservoir for continuous contamination, and efforts in the optimization of cleaning and disinfection procedures used for hemodialysis systems should aim to detach and neutralize biofilm when necessary.

Retroperitoneal nephrectomy: comparison of laparoscopy with open surgery.

Retroperitoneal laparoscopic nephrectomy (RLN) is a relatively recent technique whose performance needs to be firmly established. The aim of this study was to compare the results of RLNs in 19 patients with retrospective results for 10 cases of open surgery. Ten of the RLN patients had transplanted kidneys. We used a slightly modified, already published technique with only three trocars that did not require balloon dilatation of the retroperitoneal space. It was successful in patients with and without transplants. The average operative times of RLN and open surgery were 115 and 110 minutes, respectively. In no instance did the laparoscopic procedure need to be converted to open surgery. There were no peri- or postoperative complications that could be related to the RLN technique. The average length of hospitalization after RLN was considerably shorter (3.8 days) than after open surgery (7.9 days). In conclusion, our experience shows that RLN is a safe, reproducible technique that reduces recovery time. It has become our first-line approach for simple nephrectomy, nephroureterectomy for ureteral tumors, and removal of the native kidney in transplant recipients.

Mechanisms of postoperative prolonged plasma volume expansion with low molecular weight hydroxethy starch (HES 200/0.62, 6%).

OBJECTIVE: To define the mechanisms of the stable and prolonged post-operative plasma volume expansion observed with Hydroxyethyl Starches (HES) and to determine whether a partial intravascular hydrolysis of large molecules contribute to reinforce the colloid-osmotic effect. DESIGN: Prospective, pharmacologic study using single dose of drug. SETTING: University-based, post-anesthesia care unit. PATIENTS: The protocol was performed during the post-operative period, in 10 patients after stable recovery from general anesthesia for carotid endarterectomy. INTERVENTIONS: HES 200/0.62 (500 ml) was infused over 30 min. Standard hemodynamic and biological variables, HES concentration and colloid osmotic pressure were obtained at each measurement. Plasma volume was calculated using 51Cr-labelled RBCs. Patterns of changes in number average molecular weight (MWn) and weight average MW (MWw) were measured using gel permeation chromatography. Measurements were obtained at control, end of infusion, 1 h, 3 h, 6 h and 24 h after infusion. MEASUREMENTS AND MAIN RESULTS: Plasma volume increased by 693 ml (+21%) after the infusion of HES and remained constant over 24 h. HES concentration progressively decreased to reach a value of 35% of the peak at 24 h. MWn and MWw, initially decreased when compared with the dose solution and changed little in the 24 h study period. Diuresis significantly decreased at 3 h up to 24 h. Plasma albumin decreased after infusion and then progressively increased to reach a significantly higher value at 24 h than after infusion. CONCLUSION: Initial plasma volume expansion and decrease in HES concentration agree with previously-published data. Maintenance of plasma volume expansion over 24 h was not related to a partial intravascular hydrolysis. Low elimination rate of HES, extravascular mobilization of albumin and post-operative renal adaptations were possibly the 3 main mechanisms to explain a prolonged plasma volume expansion with HES 200/0.62, 6%.

Developing health research capability in Tanzania: from a Swiss Tropical Institute Field Laboratory to the Ifakara Centre of the Tanzanian National Institute of Medical Research.

The paper summarizes the evolution of a biomedical field research station in Tanzania, established by a European institute, into a national health research and resource centre. The Swiss Tropical Institute Field Laboratory was founded in Ifakara in the Kilombero District in southeastern Tanzania in 1957. It has evolved into the Ifakara Centre, a national but peripherally located research centre involved in applied, operational and health systems research, training, and direct health sector support activities. Since 1991, the centre has been an affiliate of the National Institute for Medical Research in Tanzania. It has achieved an autonomous status and attracts frontline priority research and high quality research teams; the ongoing phase 3 malaria vaccine trial is a recent major activity. Starting from biomedical priorities in research and training, the centre has broadened its spectrum to include social science disciplines including economics. The major determinants for this development were (i) the long-term partnership between the executing agency in the north and the partners in the south at the national level, (ii) the support of this partnership by a long-term commitment of the major funding partners, (iii) the concept that local priorities form the basis of all activities, and (iv) the linking of research and training to public health action. The last two elements are considered to be crucial for the centre's multidisciplinary approach to health research and the support of public health in Tanzania and in eastern and southern Africa.

Heterogeneous regional vascular responses to simulated transient hypovolemia in man.

OBJECTIVE: To describe the evolution of systemic and regional blood flows during and after hypovolemia in humans. DESIGN: Simulation of hypovolemia by a prolonged application of lower body negative pressure (LBNP). SETTING: Laboratory of Clinical Research, Surgical Intensive Care Unit of an University Hospital. PARTICIPANTS: 8 healthy male volunteers. INTERVENTIONS: 3 successive and increasing 15 min-levels of LBNP were followed by a progressive return (10 min) to atmospheric pressure, then a 60 min-recovery period. MEASUREMENTS AND MAIN RESULTS: Simulated hypovolemia induced a parallel one-third decrease in cardiac output (bioimpedance), musculocutaneous (venous plethysmography) and splanchnic (ICG clearance) blood flows. Adrenergic-mediated peripheral vasoconstriction prevented any change in mean arterial pressure. The decrease in renal blood flow (PAH clearance) was limited, glomerular filtration rate (inulin clearance) unchanged and thus filtration fraction increased. All the cardiovascular and biological variables returned to pre-LBNP values during the recovery period except for splanchnic blood flow which remained below control values 60 min after the return to atmospheric pressure. CONCLUSIONS: Since a sustained splanchnic vasoconstriction follows a transient normotensive hypovolemia in healthy men despite adequate treatment considering arterial pressure and cardiac output, the therapeutic goals of fluid resuscitation after hypovolemic shock might be revisited and a supranormal value of cardiac output proposed.

Community-based questionnaires and health statistics as tools for the cost-efficient identification of communities at risk of urinary schistosomiasis.

Self-administered questionnaires, distributed by existing administrative channels to village party chairmen, head-teachers and schoolchildren, showed good diagnostic performance for the qualitative assessment of urinary schistosomiasis endemicity. At a cost 34 times below that of the WHO-recommended parasitological screening strategy, the schoolchildren's questionnaire allowed the screening of 75 out of 77 schools of a rural Tanzanian district in six weeks, and the exclusion of schools not at high risk for urinary schistosomiasis with over 90% confidence. The headteacher and party questionnaires made it possible to assess the perceived importance of a spectrum of diseases and symptoms, among which was schistosomiasis. The priority rank of schistosomiasis control was strongly correlated with the prevalence rate of the disease in the community. The questionnaires also looked for the prioritization of health among other community issues and thus contributed important information for planning at district level. Standardized monthly disease reports, sent by all primary health services, were also analysed. They allowed a zonal schistosomiasis endemicity classification.

[Imported diseases in Switzerland: development and perspectives]. / Importierte Krankheiten in der Schweiz: Entwicklung und Perspektiven.

During the last years, imported diseases have become more frequent in Switzerland. This is easily explained by the enormous increase of tourism to tropical and subtropical countries. Immigration from these countries has equally seen an important augmentation. The principal imported diseases are still malaria and gastrointestinal infections. Viral infections are rarely diagnosed, with the exception of hepatitis and HIV infection. The prevalence of sexually transmitted diseases is most certainly underestimated. The differential diagnosis of imported skin diseases is still difficult. Rare tropical diseases will probably become more frequent in the coming years as travellers leave more and more the traditional tourist paths. Practitioners have to look out for such problems, and continuous training programmes for them will have to take these new problems into account. Referral centres of infectious diseases should be established in all regions of Switzerland. High priority should be given to the prevention of imported diseases.

[Imported diseases: information, communication and continuing education]. / Importierte Krankheiten: Information, Kommunikation und Fortbildung.

With the increase of international travel and immigration, imported diseases have become more important in recent years in Switzerland. Diagnosis and therapy of imported diseases were simplified over the last years, whereby prophylaxis is still a complex problem, i.e. difficult to standardize. The article analyses information problems and presents what is done in Switzerland in this regard for each concerned group (travellers, practitioners and chemists, vaccination centers). Written information and courses for continuing education are generally available and adequate, but their impact is insufficient, perhaps because of the time constraints they impose. Electronic communication systems are not yet efficient due to their low access quota (spreading and standardization of the equipment), but the situation in regard to information as well as to continuing education will be better, as soon as these systems are accessible to the large public and well adapted, easy to use programmes will have been developed.

In vitro resistance patterns of Plasmodium falciparum to chloroquine--a reflection of strain-specific immunity?

Studies in vitro among children on the response of Plasmodium falciparum to chloroquine were conducted as part of the national long-term monitoring of drug resistance in a holo- to hyperendemic malarious area of Tanzania between 1983 and 1989. Overall, no significant increase in chloroquine resistance was observed. However, in children under 5 years old resistance increased during this period, whereas in schoolchildren resistance decreased from 1986 to 1989. A hypothesis based on antigenic differences between resistant and sensitive strains is proposed to explain this age-specific pattern. If immunity develops principally against the most frequent parasite strains, then as it develops the numbers of the most frequent strains will be reduced, whilst, the rare strains may become predominant and thus be detected in the blood of immune patients. Thus, in an endemic area, the observed resistance pattern in non-immune infants will differ from that in immune schoolchildren, as was observed in the present study. These findings may have important implications for the control of malaria and the development of vaccines.

Hepatic capillariasis in a 1-year-old child.

We described the 2nd European case of hepatic capillariasis. The diagnosis of this parasitosis caused by Capillaria hepatica was made by needle biopsy of the liver in a 1-year-old girl who presented with a triad of persistent fever, hepatomegaly and hypereosinophilia. The child recovered completely after treatment with thiabendazole (Mintezol, Merck, Sharp and Dohme, Hoddeston, UK).

Ultrasound scanning for detecting morbidity due to Schistosoma haematobium and its resolution following treatment with different doses of praziquantel.

A study to assess the resolution of urinary tract morbidity due to Schistosoma haematobium was conducted on 2 cohorts of schoolchildren attending neighbouring schools in Kilombero District, southern Tanzania. Schoolchildren were screened for S. haematobium infection using the standard World Health Organization filtration technique and subsequently examined for urinary tract pathology using a portable 3.0 MHz sector scanner (Siemens Sonoline 1300). Treatment with praziquantel was given to all infected children. Children with observed urinary tract pathology received either 20 (n = 52) or 40 (n = 79) mg/kg body weight and were sonographically re-examined one, 2, 3 and 6 months following treatment. Geometric mean outputs of 21 and 19 eggs/ml of urine were detected in the 2 cohorts before treatment. Urinary tract pathology correlated positively with egg output (chi 2, P = 0.02) and microhaematuria (P = 0.0001). Bladder (wall irregularities and polyps) and kidney (congestive changes) pathologies were found in 81% and 36%, respectively, of the group that received 20 mg/kg of praziquantel, and in 78% and 46% of the group that received 40 mg/kg. Six months after treatment, 90.4% and 88.0% parasitological cure rates were obtained using 20 or 40 mg praziquantel/kg body weight. The respective pathology clearances were 88% and 91%. 20 mg/kg of praziquantel was as effective with regard to cure rates and reversibility of morbidity as 40 mg/kg.