Risk factors for burnout and depression in healthcare workers: The national AMADEUS study protocol.

CONTEXT: Burnout is an international phenomenon defined as a state of professional exhaustion. It can lead to depression and have major economic and organizational impacts. Previous studies of healthcare professionals in France have focused on physicians, but none to date have explored other healthcare professions. OBJECTIVES: The main objective of our study is to determine the prevalence of burnout among healthcare workers. The secondary objectives are to explore the associations of burnout with professional and psycho-social factors and the risk of depression, professional harassment, sexual harassment, sexual-orientation based discrimination, consumption of antidepressants, anxiolytics and also the lifestyle of the individual: smoking, alcohol consumption, coffee consumption, physical activity and sleep quality. MATERIALS AND METHODS: The survey will take the form of a voluntary and anonymous online questionnaire carried out on the FramaForm1® platform and will be disseminated via social networks, professional networks and mailings. STUDY POPULATION: Senior doctors, interns, directors of care, nurses, head nurses and senior head nurses, physiotherapists and occupational therapists, dieticians, radiology technicians, laboratory technicians, psychologists, nurses' aides, auxiliary nurses and midwives will be included. COLLECTED DATA: Burnout will be measured with the Maslach Inventory burnout (MBI) questionnaire, work environment with the Karasek questionnaire and anxiety, depression risk with the Center for Epidemiologic Studies- Depression (CES-D), physical activity with the Global Physical Activity Questionnaire (GPAQ) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). ETHICS: This protocol has been accepted by the ethical committee (IRB n°C08/21.01.06.93911, CNIL). EXPECTED RESULTS: Based on international studies, we expect a high rate of burnout with disparities according to profession, socio-demographic data, seniority and type of service. We also expect a significant rate of untreated depression. This study will provide evidence for policy makers to implement collective strategies to reduce burnout and depression in the different populations studied.

[Cardioprotection via the arm? : How a blood pressure cuff decreases infarct sizes]. / Kardioprotektion über den Arm? : Wenn eine Blutdruckmanschette den Herzinfarkt verkleinert.

Cardiovascular diseases and especially myocardial infarctions are responsible for a high morbidity and mortality throughout Europe. An essential aspect of myocardial infarction is ischemia/reperfusion injury which represents the necrosis of myocytes following reperfusion. One possible option to counteract ischemia/reperfusion injury is the much researched process of remote ischemic conditioning (RIC), whereby a certain tissue (e.g. skeletal muscle) is subjected to several cycles of short periods (e.g. 5 min) of ischemia and reperfusion and leads to the protection of another organ (e.g. the heart). Despite substantial efforts to elucidate the underlying mechanisms during the last decades, this phenomenon is not yet completely understood. Clinical studies mainly concentrated on laboratory and radiological parameters, which led to better understanding of RIC; however, large clinical studies evaluating the possible influence on mortality are still lacking. This review article provides an introduction to RIC and summarizes the current understanding of known pathomechanisms and the results of important clinical studies.

Vertebral osteomyelitis caused by Actinobaculum schaalii: a difficult-to-diagnose and potentially invasive uropathogen.

We report the first case of vertebral osteomyelitis caused by Actinobaculum schaalii and review all cases of A. schaalii identified at our institution between 2002 and 2005. A. schaalii causes urinary tract infections - especially in elderly people - occasionally with septic complications.

Mass spectrometric characterization of proteins extracted from Jurkat T cell detergent-resistant membrane domains.

Plasma membranes of most cell types are thought to contain microdomains commonly referred to as lipid rafts, biochemically distinct from bulk plasma membrane, apparently enriched for proteins involved in signal transduction. In T cells, it is believed that lipid rafts aggregate at the site of T cell receptor engagement and act as foci for initiation of the signaling process. In order to gain insight into the possible functioning of lipid rafts, we applied microcapillary liquid chromatography electrospray ionization tandem mass spectrometry (microLC-ESI-MS/MS) methodologies to the identification of proteins which copurified with lipid rafts. Following isolation of lipid rafts as Triton-insoluble, low-density membrane fractions from Jurkat T cells, tryptic digests were generated of individual protein bands resolved electrophoretically. Alternatively, cysteine-containing peptides were isolated from total tryptic digests of unseparated lipid raft proteins following labeling with a cysteine-specific biotinylation reagent and avidin affinity purification. In both cases, protein identifications were made by comparison of tandem MS spectra generated by microLC-ESI-MS/MS to both protein and DNA sequence databases using Sequest software. Proteins identified essentially fell into two groups: cytoskeletal proteins, and proteins involved in signal transduction. These findings are discussed in the light of the current understanding of both lipid raft biology and signal transduction.

The anti-idiotypic antibody to chlamydial glycolipid exoantigen (GLXA) protects mice against genital infection with a human biovar of Chlamydia trachomatis.

Despite more than three decades of anti-chlamydial vaccine research and improved vaccine strategies with new technologies, no vaccine candidate has protected against heterologous challenge, nor at more than one site of infection. The majority of experimental anti-chlamydial vaccines to date have targeted the chlamydial major outer membrane protein (MOMP). Many MOMP-directed vaccine candidates have been highly immunogenic, but have failed to protect against infectious challenge. We have extended our previous studies of a different anti-chlamydial vaccine, a monoclonal anti-idiotypic antibody (anti-Id; mAb2) which is a molecular mimic of the chlamydial glycolipid exoantigen (GLXA). The present studies demonstrate that the mAb2 vaccine is protective in a murine genital infection model utilizing a human urogenital strain. After either mucosal (oral or intranasal) or systemic (subcutaneous) immunization with the poly (lactide) encapsulated-mAb2 to GLXA, C3H/HeJ mice were significantly protected against topical vaginal challenge with Chlamydia trachomatis (K serovar; UW-31). Reduced vaginal shedding of organism and genital tract inflammation were associated with GLXA-specific and/or anti-EB neutralizing serum antibody. Our results demonstrate that the anti-Id (mAb2) vaccine is protective against an additional human biovar of C. trachomatis in C3H/HeJ mice, which are allogeneic to the source of mAb2 (BALB/c).

[Interferon beta-1b (Betaferon)therapy in patients with relapsing-remitting multiple sclerosis: findings of a prospective, multi-center study of disease progression]. / Interferon beta-1b (Betaferon) bei Patienten mit schubförmig-remittierender Multipler Sklerose. Ergebnisse einer prospektiven, multizentrischen Verlaufsbeobachtung.

In a survey of disease course, the efficacy and tolerability of 24-month interferon beta-1b therapy for relapsing remitting multiple sclerosis (RRMS) were evaluated in 410 patients. The investigation aimed at obtaining data from general practice and of possibly unknown, unexpected adverse reactions. In the 241 patients still on therapy, efficacy was rated after 24 months as "good" or "very good" in 75% of cases. After 24 months, 36.9% of the patients had no exacerbation (baseline 0.3%). Annual exacerbation rates dropped from 1.5 before treatment to 0.7 in the second treatment year. In the 2 years before treatment, 66.2% had worsened by at least 0.5 points on the extended disability status scale (EDSS). This proportion was reduced to 41.2% after 2 years of treatment. The safety profile corresponded to results from controlled trials. This postmarketing survey supports data from the published controlled interferon beta-1b studies and confirms the main effects of this therapy under routine conditions in general practice.

[Hospitalizations in a cohort of 175 severely drug-addicted patients of a medically managed opiate withdrawal project]. / Hospitalisationen in einer Kohorte von 175 schwer drogenabhängigen Patienten eines ärztlich betreuten Opiatabgabeprojektes.

In this study we investigated a population of 175 seriously drug addicted patients. They were randomised in a controlled opiate maintenance program in Basel, Switzerland. We investigated hospitalizations in the time period three years before entry into the program and approximately 3.5 years after entry into this program. The mean age was 28.4 years, the mean drug injection time was 8.8 years. 82.6% of the patients were seropositive for HCV and 21.5% were HIV-infected. We observed 223 hospitalizations in 100/175 patients during the observation period of 6.5 years. Most commonly infections (n = 94), different diseases of internal medicine (n = 44) and surgical diseases (n = 41) led to hospitalization. Altogether, we found no decrease of the incidence of hospitalisations. However, there was a significant decrease of directly drug-induced diseases (p < 0.05). So far, hospitalizations did not diminish in this well-controlled opiate maintenance program. However, as shown in earlier studies, the incidence of HIV drastically dropped. Hence, it may be that a longer follow-up may prove beneficial regarding the incidence of hospitalisations.

Long-term vaginal antibody delivery: delivery systems and biodistribution.

Topical delivery systems can provide prolonged delivery of antibodies to the vaginal mucosal surface for long-term protection against infectious diseases. We examined the biodistribution of antibodies during 30 days of vaginal antibody delivery in mice. Different antibody preparations (including monoclonal IgG and IgM, as well as several different (125)I-labeled IgGs) were administered by polymer vaginal rings, which were designed to provide continuous antibody delivery. Antibody concentrations remained high in the vaginal secretions for up to 30 days after disk insertion; radiolabeled antibody was also found, at approximately 100 times lower concentration, in the blood and other tissues. The measured concentrations agreed reasonably well with a simple pharmacokinetic model, which was used to calculate mucosal and systemic concentrations as a function of antibody delivery and elimination rates. Results from the model were consistent with previously reported antibody pharmacokinetic measurements: the half-life for antibody elimination for the vagina was approximately 3 h; the half-life for IgG(1) clearance from the blood was >1 day; and the overall permeability constant for vaginal uptake of IgG was approximately 0.01 to 0.03 h(-1). These results provide important information for the design of controlled antibody delivery devices for vaginal use, and suggest that high-dose, long-term vaginal administration of antibodies may be a reasonable approach for achieving sustained mucosal and systemic antibody levels.

Proton magnetic resonance spectroscopy in Kennedy syndrome.

OBJECTIVE: To seek regional metabolite abnormalities in patients with Kennedy disease (KD) using proton magnetic resonance spectroscopy. DESIGN: Nine patients with KD showing the typical phenotype without clinical signs of upper motor neuron involvement were compared with 17 male, age-matched, healthy control subjects. Relative metabolite concentrations for N-acetyl (NA) groups, choline-containing groups (Cho), phosphocreatine (Cr), and lactate (Lac) were determined in the brainstem and the motor region. RESULTS: Pathologic Lac signals suggesting impaired energy metabolism were absent in patients and controls. In the brainstem area, patients with KD showed a significant reduction in the NA/Cho metabolite ratio (P = .01). In the motor region, NA/Cho (P = .04) and NA/Cr (P = .03) ratios were significantly reduced. The reduction of the NA/Cho ratio in the motor region mainly resulted from decreased metabolite ratios in 3 patients. Changes in metabolite ratios did not correlate with the number of trinucleotide cytosine-adenine-guanine repeats from leukocytes. Because of the relatively small sample size due to the rarity of KD, these results should be considered preliminary. CONCLUSIONS: Spectroscopic data fail to provide further evidence for altered energy metabolism in KD. Metabolite changes in the brainstem indicate a reduction of the neuronal marker NA or elevated Cho. These findings may reflect neuronal loss or gliosis consistent with the known pathologic features. In a subset of patients, altered metabolite ratios best explained by neuronal loss suggest subclinical involvement of the motor region. The extent of metabolite changes does not correlate with the trinucleotide repeat length.

SPECT study of a German CADASIL family: a phenotype with migraine and progressive dementia only.

OBJECTIVE: We describe the clinical, molecular, genetic, MRI, and SPECT features of a German family with autosomal dominant migraine and dementia, mapping to the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) locus. We studied the correlation of cerebral blood flow, MRI, and cognitive function. BACKGROUND: CADASIL is a small-vessel disease of the brain mapped to chromosome 19p13.1. Mutations of the Notch3 gene cause this disorder. Most phenotypes are characterized by transient ischemic attacks (TIAs) and lacunar strokes leading to dementia. Migraine is frequent. A single photon emission computed tomographic (SPECT) study of this disorder has not yet been published. METHODS: We studied 13 individuals clinically and performed neuroimaging studies with MRI and SPECT. RESULTS: Genetic analysis strongly supported linkage to the CADASIL locus, and the disease haplotype was found in six individuals. Analysis by single-strand confirmation polymorphism did not identify Notch3 mutations. All affected individuals had MRI white matter hyperintensities and four individuals had additional basal ganglial signal abnormalities. Four affected individuals had migraine, two of whom had slowly progressive dementia. TIAs, stroke, and focal neurologic signs were absent. Cerebral blood flow reduction in SPECT studies of affected individuals matched with MRI signal abnormalities. Cognitive impairment was linked to signal abnormalities and hypoperfusion in the basal ganglia. Demented patients had a pattern of frontal, temporal, and basal ganglial hypoperfusion. CONCLUSIONS: We describe a CADASIL phenotype that is characterized by the absence of focal neurologic symptoms and present the first SPECT study of this disorder.

Ligand preferences of kringle 2 and homologous domains of human plasminogen: canvassing weak, intermediate, and high-affinity binding sites by 1H-NMR.

The interaction of various small aliphatic and aromatic ionic ligands with the human plasminogen (HPg) recombinant kringle 2 (r-K2) domain has been investigated by 1H-NMR spectroscopy at 500 MHz. The results are compared against ligand-binding properties of the homologous, lysine-binding HPg kringle 1 (K1), kringle 4 (K4), and kringle 5 (K5). The investigated ligands include the omega-aminocarboxylic acids 4-aminobutyric acid (4-ABA), 5-aminopentanoic acid (5-APA), 6-aminohexanoic acid (6-AHA), 7-aminoheptanoic acid (7-AHA), lysine and arginine derivatives with free and blocked alpha-amino and/or carboxylate groups, and a number of cyclic analogs, zwitterions of similar size such as trans-(aminomethyl)cyclohexanecarboxylic acid (AMCHA) and p-benzylaminesulfonic acid (BASA), and the nonzwitterions benzylamine and benzamidine. Equilibrium association constant (Ka) values were determined from 1H-NMR ligand titration profiles. Among the aliphatic linear ligands, 5-APA (Ka approximately 3.4 mM-1) shows the strongest interaction with r-K2 followed by 6-AHA (Ka approximately 2.3 mM-1), 7-AHA (Ka approximately 0.45 mM-1), and 4-ABA (Ka approximately 0.22 mM-1). In contrast, r-K1, K4, and K5 exhibit a preference for 6-AHA (Ka approximately 74.2, 21.0, and 10.6 mM-1, respectively), a ligand approximately 1.14 A longer than 5-APA. Mutations R220G and E221D increase the affinity of r-K2 for these ligands but leave the selectivity profile essentially unaffected: 5-APA > 6-AHA > 7-AHA > 4-ABA (Ka approximately 6.5, 3.9, 1.8, and 0.74 mM-1, respectively). We find that, while r-K2 definitely interacts with Nalpha-acetyl-L-lysine and L-lysine (Ka approximately 0.96 and 0.68 mM-1, respectively), the affinity for analogs carrying a blocked carboxylate group is relatively weak (Ka approximately 0.1 mM-1). We also investigated the interaction of r-K2 with L-arginine (Ka approximately 0.31 mM-1) and its derivatives Nalpha-acetyl-L-arginine (Ka approximately 0.55 mM-1), Nalpha-acetyl-L-arginine methyl ester (Ka approximately 0.07 mM-1), and L-arginine methyl ester (Ka approximately 0.03 mM-1). Zwitterionic gamma-guanidinobutyric acid, containing one less methylene group than arginine, exhibits a Ka of approximately 0.28 mM-1. The affinity of r-K2 for lysine and arginine derivatives suggests that K2 could play a role in intermolecular as well as intramolecular interactions of HPg. As is the case for the HPg K1, K4, and K5, among the tested ligands, AMCHA is the one which interacts most firmly with r-K2 (Ka approximately 7.3 mM-1) while the aromatic ligands BASA, benzylamine, and benzamidine exhibit Ka values of approximately 4.0, approximately 0.04, and approximately 0.03 mM-1, respectively. The relative stability of these interactions indicates a strict requirement for both cationic and anionic polar groups in the ligand, whereas the presence of a lipophilic aromatic group seems to be of lesser consequence. Ligand-induced shifts of r-K2 (1)H-NMR signals and two-dimensional nuclear Overhauser effect (NOESY) experiments in the presence of 6-AHA reveal direct involvement of residues Tyr36, Trp62, Phe64, and Trp72 (kringle residue numbering convention) in ligand binding. Starting from the X-ray crystallographic structure of HPg K4 and the intermolecular 1H-NMR NOE data, two models of the K2 lysine binding site complexed to 6-AHA have been derived which differ mainly in the extent of electrostatic pairing between the K2 Arg56 and Glu57 side chains. Competition between these two conformations in equilibrium may account for the relatively lesser affinity of the K2 domain for zwitterionic lysine-type ligands.

Conversion to microemulsion cyclosporine in stable renal transplant patients: results after one year.

We switched 302 renal transplant patients from the conventional to a new microemulsion formulation of cyclosporine, to study the latter's safety and efficacy. We used a simple 1:1 conversion of the patient's total daily dose. We measured trough drug levels as well as serum creatinine, liver enzymes, uric acid, and blood pressure values at baseline and at days 4, 8, 15, 29, and months 3, 6 and 12 after drug substitution. Dose adjustments directed at trough levels 80-120 ng/ml were performed, starting at day 8. Within the 12-month observation period, the cyclosporine dose was reduced by 14.7% (204 +/- 60 mg/day baseline vs 174 +/- 51 mg/day after conversion, p < or = 0.001). By day 8, the 1:1 dosage conversion resulted in a modest mean increase in drug trough levels (114 ng/ml baseline vs 120 ng/ml, p < or = 0.01). This increase was accompanied by an increase in serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in uric acid values (p < or = 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decreased (p < or = 0.05). After one month, drug trough levels had decreased to baseline (112 ng/ml) and remained there until month 6. They were significantly lower after 12 months (102 +/- 33 ng/ml, p < or = 0.001). Plasma creatinine values decreased to below baseline by month 6 (p < or = 0.001) and month 12 (p < or = 0.001). Twenty-four (8%) biopsy proven rejection episodes and 7 cases of cyclosporine attributed nephrotoxicity occurred in these 302 patients within these 12 months. We conclude, that a 1:1 conversion from conventional to the microemulsion form of cyclosporine is efficacious and safe. However, we advise an initial 10% decrease in dose reduction in those patients whose trough levels are in the high-normal range.

Substitution of conventional cyclosporin with a new microemulsion formulation in renal transplant patients: results after 1 year.

BACKGROUND: A new galenic form of cyclosporin A has been developed, based on microemulsion technology. The bioavailability of the compound is relatively independent of food intake and bile flow. It was the purpose of this prospective clinical trial to study the safety of the microemulsion form of cyclosporin A. METHODS: Three hundred and two renal transplant patients, stratified according to transplant age, were switched from the conventional to the new microemulsion formulation of cyclosporin A. A 1:1 conversion ration was used. Measurements included CsA levels, S-creatinine, liver enzymes, uric acid, and blood pressure. Measurements were performed at baseline and on days 4, 8, 15, 29 and months 3, 6 and 12 after conversion. Dose adjustments were performed to achieve through levels of 80-120 ng/ml. RESULTS: Within the 12-month observation period the cyclosporin dose was reduced by 14.7% (from 204 +/- 60 mg/day at baseline to 174 +/- 51 mg/day after conversion, P < 0.001). Acutely, i.e. by day 8, 1:1 dose conversion resulted in a modest increase of mean drug through levels (from 114 ng/ml at baseline to 120 ng/ml, P < 0.01). This increase was accompanied by an increase in serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in uric acid values (P < or = 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decrease (P < 0.05). After 1 month, drug through levels had decreased to baseline (112 ng/ml) and remained there until month 6. They were significantly lower after 12 months (102 +/- 33 ng/ml), P <0.001). Creatinine clearance values increased to above baseline at 6 and 12 months. Within the 1-year period there occurred 24 (= 8%) episodes of biopsy proven rejection and seven episodes of cyclosporin-attributed nephrotoxicity. CONCLUSIONS: The 1:1 conversion from conventional cyclosporin A to the microemulsion formulation s efficacious and safe, but an initial dose reduction of 10% is advised in patients with through levels in the high-normal range.

Clinical experience transferring kidney transplant patients from Sandimmun to Sandimmun Neoral--results after 3 months.

The new galenic formulation of cyclosporine prepared as microemulsion (Sandimmun Neoral, SN) shows a significantly improved correlation between both trough level (Cmin) and dose. Moreover, since the bioavailability is increased by 20 to 30% on average, it may lead to a drug overexposure in so far malabsorbing patients. In order to assess safety and to establish an appropriate procedure to switch patients safely from conventional Sandimmun to SN, we initialized an open, stratified (transplant age) clinical trial enrolling 302 patients of our outpatient clinic. We used a simple 1:1 conversion of the patient's total daily dose. Trough drug levels, as well as serum creatinine, liver enzymes, uric acid, and blood pressure values were measured at baseline, at days 4, 8, 15, 29, and at month 3 after drug substitution. Within the three month observation period, the cyclosporine dose was reduced by 14.2% (204 +/- 60 mg/day baseline vs. 175 +/- 54 mg/day after conversion, p < 0.05). By day 8, the 1:1 dosage conversion resulted in a modest mean increase in drug trough levels (114 ng/ml baseline vs. 120 ng/ml, p < 0.05). This increase was accompanied by a slight increase in mean serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in mean uric acid values (p < 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decreased (p < 0.05). Parallel to dosage reduction, drug trough levels had decreased after 1 month to baseline (112 ng/ml) and remained there for the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult polyglucosan body myopathy.

This report describes a sporadic late-onset myopathy in two unrelated adults which was marked by polyglucosan inclusions surrounded by abnormally structured mitochondria, the latter finding a localized, possibly reactive phenomenon. The polyglucosan material was characterized by a battery of histochemical and enzyme histochemical techniques; revealed common antigenicity with Lafora bodies, corpora amylacea and muscle fiber inclusions in types IV and VII glycogenoses; and contained ubiquitin. Additional lectin histochemical and associated digestion preparations disclosed the presence of alpha-glycosyl residues as apparently the sole carbohydrate component in polyglucosan bodies while the above mentioned common antigenicity with Lafora bodies and other inclusions suggests an additional, so far unidentified, protein component.