[Anticholinergic scales: Use in psychiatry and update of the anticholinergic impregnation scale]. / Les échelles anticholinergiques : usage en psychiatrie et mise à jour de l'échelle d'imprégnation anticholinergique.

Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Herein, we propose a narrative literature review describing: (i) cholinergic pharmacology and anticholinergic properties; (ii) the importance of anticholinergic therapeutic properties in psychiatry; (iii) the existing anticholinergic drug scales and their usage limitations in Psychiatry and; last (iv) an update to the anticholinergic drug impregnation scale, designed for the French psychiatry practice. The anticholinergic side effects can appear both in the peripheral level (dry mouth, constipation, etc.) and in the central level (especially as cognitive deficits). Many of the so called « anticholinergic ¼ drugs are in fact entirely or mostly antimuscarinic and act essentially as parasympathetic system antagonists. Overall, anticholinergic/antimuscarinic side effects are usually attributed to psychotropic medications: to certain antipsychotics, notably classical neuroleptics such as phenothiazine and also to tricyclic antidepressants. In practice, the impact of anticholinergic toxicity treatments is often highlighted due to their excessively prolonged use in patients on antipsychotics. Interestingly, these antipsychotic treatments are better known for their anticholinergic side effects, especially cognitive ones, with an early onset specially in elder patients and/or in the case of polymedication. In order to evaluate anticholinergic side effects, metrics known as anticholinergic burden scales were created in the last few decades. Nowadays, 13 different scales are documented and accepted by the international academic community, but only three of them are commonly used: the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB). All of them are based on a similar principle, consisting of grading treatments individually, and they are normally scored from 0 - no presence of side effects - to 3 - anticholinergic effects considered to be strong or very strong. Using these scales enables the calculation of the so-called "anticholinergic burden", which corresponds to the cumulative effect of using multiple medications with anticholinergic properties simultaneously. The application of anticholinergic scales to patients with psychiatric disorders has revealed that schizophrenic patients seem to be especially sensitive to anticholinergic cognitive side effects, while elder and depressed patients were more likely to show symptoms of dementia when exposed to higher anticholinergic burden. Unfortunately, these tools appear to have a low parallel reliability, and so they might induce large differences when assessing side effects predictability. In addition, the capacity of these scales to predict central adverse effects is limited due to the fact they poorly or do not differentiate, the ability of treatments to cross the blood-brain barrier. Finally, one last limitation on the validity of these scales is prescription posology is not accounted for side effects considered to be dose dependent. Recently, the MARANTE (Muscarinic Acetylcholine Receptor ANTagonist Exposure) scale has incorporated an anticholinergic burden weighting by posology. Nevertheless, this new model can be criticized, due to the limited number of medications included and due to testing a limited number of potency ranges and dosages for each treatment. Herein, we propose an update to the Anticholinergic Impregnation Scale, developed specifically for the French Psychiatry practice. The scale validation was based on an evaluation of the prescriptions correcting anticholinergic peripheral side effects (constipation, xerostomia and xeropthalmia). This indirect evaluation allowed us to show patients with an anticholinergic impregnation score higher than 5 received significantly more treatments for constipation and xerostomia. This strategy bypasses the bias of a cognitive evaluation in patients with severe mental health disorders. Moreover, the relevance of a tool developed specifically for French psychiatry is justified by the fact that some highly prescribed treatments for mental illness in France (cyamemazine and tropatemine) are strong anticholinergics, and also by the fact they are rarely included in the existing anticholinergic scales. This update of the original scale, published in 2017, includes information whether prescribed drugs cross the blood-brain barrier and thus makes possible a more accurate assessment when evaluating anticholinergic central side effects. Finally, the anticholinergic impregnation scale will soon be integrated into a prescription help software, which is currently being developed to take into consideration dose dependent adverse effects.

[Pharmaco-therapeutic evaluation of medical treatments of adult autistics and multi-handicapped patients in a public mental health unit]. / Les traitements psychotropes prescrits dans un établissement public de santé mentale accueillant des personnes atteintes d'autisme et des polyhandicapés.

INTRODUCTION: This paper presents a survey conducted on a population of multi-handicapped patients and autistic adults hospitalised long term in the Paul Guiraud mental health Hospital in Villejuif France. OBJECTIVE: The aim of the survey is to deepen the knowledge of the treatments for this specific population. METHODS: A preliminary medical investigation was conducted on the population in order to target different groups of patients. Once patients had listed and defined their medical needs, prescriptions were analysed to assess whether clinical characteristics had an impact. Thus, the analysis of treatments was carried out for the 57 patients (14% of the hospital population) and compared to other investigations conducted on the population commonly hospitalised in Psychiatry. The evaluation of the treatments was obtained through a questionnaire which enabled us to target the therapeutical goals and to obtain additional clinical information. The drugs with a high rate of prescription were compared between the autistic group and the multi-handicapped group. The important comorbidity and the multi-symptomatology of autism often involves the polymedication of these patients (8+/-0.8 drugs per patient). RESULTS: Fifty per cent of the treatments are referred to as somatic treatments. The average length of stay (22.3 years) and the high average age are aggravating factors for polymedication. The average number of psychotropic molecules also appears higher than in the populations studied in the literature. The heterogeneity of clinical forms of autism and polyhandicap encourages prescribers to multidrug therapy. The prescriptions usually remain stable (17.5% of psychiatric treatment is adapted and only 7% of somatic treatment). Epilepsy and constipation are the main treated somatic disorders. In psychiatry, the oral route is the privileged route of administration (81% of treatments) with, more specifically, the use of drinkable solutions for the psychiatric treatment. Neuroleptic drugs are the basic treatment of these patients (82% of prescriptions). The aim of the prescription of neuroleptics is essentially to obtain behavioural or antipsychotic sedation. Cyamemazin is the most prescribed drug (46% of neuroleptic prescriptions), mainly for its anxiolytic effects. Co-prescription is frequent (55.3%) and corresponds to 53% of co-prescriptions of an association of phenothiazine and butyrophenone. Doses are high, which implies the prescription of treatments against the neuroleptics side-effects (86% of patients have such a prescription). The rate of prescriptions of the other psychotropic drugs (hypnotics, anxiolytics, etc.) is approximately equivalent between our population and the "classical" hospitalised psychiatric population, except for antidepressants (7% of prescriptions) because the differential diagnosis is difficult in these patients. Nearly 60% of patients have prescriptions of hypnotic drugs. However, this figure is tempered by prescriptions of drugs "if necessary" in two-thirds of the cases. Finally, only 30% of patients have systematic hypnotic prescriptions. CONCLUSION: Although autistics are clinically different from multi-handicapped patients, no statistically significant difference was demonstrated in their prescriptions, which implies a similar pharmacological management. It is difficult to clearly distinguish these two populations only according to the type of drugs used and the doses prescribed.

Grimontia hollisae, a potential agent of gastroenteritis and bacteraemia in the Mediterranean area.

Vibrio hollisae was first described in 1982 as an agent of diarrhoea and was reclassified in 2003 into a novel genus as Grimontia hollisae. We report the first case of G. hollisae bacteraemia in the Mediterranean area, in an 81-year-old man with a severe gastroenteritis and hepatitis following the consumption of raw oysters. The incidence of this micro-organism as an agent of gastroenteritis may be underestimated because it may not be detected using routine culture conditions.

Severe hemorrhagic syndrome due to similarity of drug names.

The names of many drugs look or sound like those of other drugs, which leads to confusion and potentially harmful medication errors. We report a nearly fatal permutation between two drugs including a vitamin K antagonist that resulted in a 68-year-old man being admitted to the emergency department with severe, spontaneous hemorrhagic syndrome. Such problems can be alleviated through actions by regulatory agencies, pharmaceutical manufacturers, health care professionals, and patients.

[Clinical implications of high cobalamin blood levels for internal medicine]. / Implications cliniques de la découverte d'une hypervitaminémie B12 en médecine interne.

PURPOSE: The high incidence of cobalamin (vitamin B12) deficiency results in frequent dosages of this vitamin in a department of internal medicine may reveal paradoxically high blood levels of cobalamin. The objective of the study was to estimate underlying diseases and potential diagnostic relevance of high cobalamin blood levels in internal medicine. METHODS: A retrospective study was conducted, including in-patients from December 2005 to July 2006 presenting high cobalamin blood levels, as determined with our laboratory normal values (200-950 pg/mL). RESULTS: High cobalamin blood level is not unusual (18.5% of all dosages) and, most of time, it is associated with one or several diseases, among which acute and chronic liver diseases (often of alcoholic origin), various neoplasias, malignant hemopathies (myelodysplasia, myeloproliferative diseases, multiple myeloma), renal insufficiency and transient hematologic abnormalities (neutrophilic hyperleucocytosis, hypereosinophilia). Vitamin B12 supplementation and chronic myeloid leukemia represent less than 5% of all hypervitaminemia. There is no correlation between the level of cobalamin blood level and the number of underlying diseases for each patients. However, very high cobalamin blood levels (>1275 pg/mL) are significantly associated to malignant hemopathies (p<0.05). It is noteworthy that most of diagnosed neoplasia were unknown and at a non-metastatic stage. CONCLUSION: Very high cobalamin blood levels are significantly associated to malignant hemopathies among the population of a department of internal medicine. Referent laboratory should actively advertise the numerous diseases involved with high cobalamin blood levels.

[Auto-immune hepatitis and antiphospholipids]. / Etude de l'association hépatite auto-immune et antiphospholipides.

INTRODUCTION: Only few series have reported the association of autoimmune hepatitis with antiphospholipid antibodies. The aim of our study is to investigate the frequency of these antibodies in a series of autoimmune hepatitis and to search for a correlation with clinical, biological or histological characteristics. MATERIAL AND METHODS: Antiphospholipid were investigated in 24 patients with well defined autoimmune hepatitis. Characteristics were compared between antiphopholipids positive and negative patients. Characteristics of our patients were also compared toward cases collected in a literature review. RESULTS: The frequency of antiphospholipid antibodies is of 70.8% in our series. Four patients had a well defined antiphospholid syndrome. Seven patients had a systemic lupus erythematosus in the antiphospholipid group whereas none in the antiphospholipid negative group. The frequency of the different antiphopholipid antibodies was: IgG ACL (52.9%), IgM APE (52.9%), ACC (43.7%), IgG Abeta2GP1 (41.2%). We found no correlation between hypergammaglobulinemia and the presence or the isotype of antiphospholipid antibodies. Clinical presentation and outcome as biological and histological parameters were similar in both groups. CONCLUSION: Our study report a high frequency of antiphospholipids antibodies in autoimmune hepatitis patients. However we found no clinical, biological or histological correlation with the presence of antiphospholipids. Further longitudinal studies on larger cohorts should clarify the association between antiphospholipid antibodies and autoimmune hepatitis and potential therapeutic issues.

Polymorphisms in the CLCN7 gene modulate bone density in postmenopausal women and in patients with autosomal dominant osteopetrosis type II.

CONTEXT: Genetic factors are important determinants of bone mineral density (BMD). The fact that mutations in the ClC-7 chloride channel cause autosomal dominant osteopetrosis (ADOII) make the CLCN7 gene an attractive candidate for the regulation of bone density. OBJECTIVE: The objective of the study was to investigate the association between polymorphisms in the CLCN7 gene and BMD in postmenopausal women and with clinical variability in ADOII. DESIGN: This was a genetic association study using five single-nucleotide polymorphisms and a variable number tandem repeat (VNTR) polymorphism in the CLCN7 gene. PARTICIPANTS: A total of 425 postmenopausal women aged 64 +/- 7 yr participated in the study. We also investigated an ADOII family with low penetrance comprising 18 mutation carriers. MAIN OUTCOME MEASURE(S): In our postmenopausal cohort, individual single-nucleotide polymorphism genotypes and haplotypes were analyzed for association with BMD at the lumbar spine and the femoral neck and with the bone resorption marker deoxypyridinoline (D-Pyr/Crea). The same polymorphisms on the nonmutated CLCN7 allele were investigated for association with the variability of the ADOII phenotype. RESULTS: Analysis by multiple linear regression revealed a significant association between the ss genotype of the VNTR and higher Z-score values (P = 0.029). The haplotype 4, which comprises the long allele of the VNTR, was found to be significantly associated with lower femoral neck Z-score values (P = 0.011). Furthermore, we found an association of the ss genotype of the VNTR with lower levels of the bone resorption marker D-Pyr/Crea (P = 0.015), whereas haplotype 4 was associated with higher D-Pyr/Crea levels (P = 0.039). In the ADOII family, we could demonstrate that haplotype 3, which contains the s-allele of the VNTR, is associated with a slightly higher probability that mutation carriers develop osteopetrosis (P = 0.029). In both cases the association seems largely to be driven by the VNTR genotype but is further strengthened if surrounding polymorphisms are added to the analysis. CONCLUSION: We observed a significant association of CLCN7 polymorphisms with the variance of BMD and bone resorption marker levels in postmenopausal women and with the variability of the ADOII phenotype.

Contribution of systematic serological testing in diagnosis of infective endocarditis.

Despite progress with diagnostic criteria, the type and timing of laboratory tests used to diagnose infective endocarditis (IE) have not been standardized. This is especially true with serological testing. Patients with suspected IE were evaluated by a standard diagnostic protocol. This protocol mandated an evaluation of the patients according to the modified Duke criteria and used a battery of laboratory investigations, including three sets of blood cultures and systematic serological testing for Coxiella burnetii, Bartonella spp., Aspergillus spp., Legionella pneumophila, and rheumatoid factor. In addition, cardiac valvular materials obtained at surgery were subjected to a comprehensive diagnostic evaluation, including PCR aimed at documenting the presence of fastidious organisms. The study included 1,998 suspected cases of IE seen over a 9-year period from April 1994 to December 2004 in Marseilles, France. They were evaluated prospectively. A total of 427 (21.4%) patients were diagnosed as having definite endocarditis. Possible endocarditis was diagnosed in 261 (13%) cases. The etiologic diagnosis was established in 397 (93%) cases by blood cultures, serological tests, and examination of the materials obtained from cardiac valves, respectively, in 348 (81.5%), 34 (8%), and 15 (3.5%) definite cases of IE. Concomitant infection with streptococci and C. burnetii was seen in two cases. The results of serological and rheumatoid factor evaluation reclassified 38 (8.9%) possible cases of IE as definite cases. Systematic serological testing improved the performance of the modified Duke criteria and was instrumental in establishing the etiologic diagnosis in 8% (34/427) cases of IE.

Escherichia coli endocarditis: seven new cases in adults and review of the literature.

Described here are seven new cases of infective endocarditis due to Escherichia coli, including four involving prosthetic valves, followed by a review of similar cases in the literature. The review identified cases according to the modified Duke's criteria and revealed 16 cases reported before 1960, 5 between 1960 and 1980, and 11 after 1980. Currently, patients diagnosed with E. coli endocarditis are older than the patients diagnosed before 1960 (p<0.05), and they are often diabetic with underlying heart disease. Prosthetic valves are frequently involved (p<0.05), and the principal source of infection is the urinary tract. Surgery is often necessary. The mortality rate associated with this type of infection has decreased since 1960, but it remains high, with 17% calculated for the present series of seven new cases. The data presented here suggest that elderly patients with prior valve disease or prosthetic valve and E. coli urinary tract infection should be examined for endocarditis.

Evaluation of antibiotic susceptibilities of Ehrlichia canis, Ehrlichia chaffeensis, and Anaplasma phagocytophilum by real-time PCR.

We determined MICs of antibiotics against Anaplasma phagocytophilum, Ehrlichia chaffeensis, and Ehrlichia canis by real-time quantitative PCR. The doubling times of the organisms were established: 19 h for E. chaffeensis, 26 h for A. phagocytophilum, and 28 h for E. canis. In comparison to the reference method for determining sensitivities, which uses Diff-Quick staining, our PCR assay was very sensitive and specific. We confirmed that doxycycline and rifampin are highly active against these bacteria and found variable susceptibilities to fluoroquinolones; A. phagocytophilum was susceptible, but E. canis and E. chaffeensis were only partly susceptible. Beta-lactam compounds, cotrimoxazole, macrolide compounds, and telithromycin showed no activity against any of the three organisms. Thiamphenicol was found to be more active than chloramphenicol. For the first time, we showed that these three species have numerous point mutations in their 23S RNA genes, with those at positions 754, 2057, 2058, 2059, and 2611 (Escherichia coli numbering) known to confer resistance to macrolide compounds in other bacteria. The role of each of these mutations in resistance to these drugs should be investigated in the future. Our study confirms previous reports that quantitative PCR is a reliable method for determining antibiotic susceptibility; therefore, it might be useful for screening new drugs.

[Acute postpartum anaemia. Clinical practice and interest of intravenous iron]. / Anémies sévères du post-partum immédiat. Pratique clinique et intérêt du fer par voie intraveineuse.

OBJECTIVES: Postpartum anaemia is a very frequent pathology concerning from 4% to 27% of patients. The purpose of this study was to estimate clinical practice in front of acute postpartum anaemia and to value a new treatment: intravenous iron. PATIENTS AND METHODS: Retrospective study over a period of 2 years (April 2001-March 2003) realised in the Department of Gynaecology and Obstetrics of Belfort Regional Hospital. Two hundred and seventeen patients were included (5% of deliveries in the same period) with immediate postpartum period haemoglobin <8 g/dl. Two groups were individualised according to the availability or not of an intravenous iron therapy. Clinical and biologic elements concerning deliveries were analysed. RESULTS: Average haemoglobin values, from delivery to 48 h after it, were 5.81 g/dl for blood-transfused patients, 6.88 g/dl for intravenous iron treated patients and 7.43 g/dl for oral iron treated patients. Fifteen patients were transfused during the year before the launch of intravenous iron as a possible therapy and only five patients the next year. The benefit of haemoglobin values with an intravenous iron therapy was 1.9 g/dl on 7 days and 3.1 g/dl on 14 days. DISCUSSION AND CONCLUSION: These results suggest a real efficiency of intravenous iron therapy for acute postpartum anaemia (haemoglobin values <8 g/dl) with a good tolerance. Patients with haemoglobin values <7 g/dl treated by intravenous iron tend to show that some blood transfusions would be thereby avoided even though blood transfusion remains the urgency treatment.

[Shrinking lung syndrome and systemic auto-immune disease]. / Le syndrome des poumons rétractés et les maladies auto-immunes.

INTRODUCTION: Shrinking lung syndrome usually manifest in dyspnea, decreased lung volume associated with elevated diaphragm. It reports with systemic autoimmune disease and physiopathological mechanism is controversial. EXEGESIS: We report three shrinking lung syndrome observations in which two cases were diagnosed at the time to onset of autoimmune disease. The three patients were treated with corticosteroid, two of them necessitated theophylline. Review of the literature highlight 60 cases and permit to discuss physiopathological mechanisms which remain uncertain. Diaphragmatic dysfunction (because of myositis or neuropathy) represented by abnormal transdiaphragmatic pressures is actually discussed. CONCLUSION: Shrinking lung syndrome is rare but must be considered in patient with autoimmune disease and dyspnea. The diagnosis can be difficult because of clinical, pathological and functional features which are controversial. The optimum treatment is unknown.

Streptococcus pneumoniae endocarditis: persistence of DNA on heart valve material 7 years after infectious episode.

We amplified by PCR and sequenced Streptococcus pneumoniae rpoB from DNA of the cardiac valve of a man who had presented with pneumococcal endocarditis 7 years earlier. Histopathologically, the valve did not show evidence of endocarditis. This case raises the question of persistence of DNA without any evidence of infection.

[Value of trimeprazine among hypnotics in a psychiatric facility]. / Place de l'alimémazine parmi les hypnotiques dans un établissement de soins psychiatriques.

Trimeprazine (TPZ) has been marketed in France since 1959, as tablets and solution containing respectively 5 mg and 40 mg/ml. TPZ is a phenothiazine derivative with known antihistaminic and sedative effects. The first approved indication for TPZ is in the treatment of allergy. However, its frequent sedative effects are undesirable in this indication. The second approved indication is in the treatment of insomnia (5-20 mg/day) and TPZ is an alternative to conventional hypnotics as diazepam, flunitrazepam, zolpidem, butobarbital... Due to the prescription frequency of this medicine in our hospital, we analyzed the naturalistic prescriptions mode and the clinical end point in patients hospitalized for mental illness. On the one hand, using the hospital prescription software, we analyzed: prescriptions frequency, dose regimen and drug associations with hypnotics, anxiolytics and sedative antipsychotics. On the other hand, we came into contact with physicians in order to know their opinion on TPZ and the whole point of that indication. The results showed a very high prescription frequency (139/400 patients; 35%), a marked increase in dose compared to those approved by the French Drug Administration (5-20 mg/day: 5%; 20-200 mg/day: 95%) and main drug association with hypnotics, tranquilizers or antipsychotics, respectively 38%, 65% and 91%. Clinical end points are: non addictive properties and an easily adequation of posology for the drinkable drop form in contrast with tablets. Thus, TPZ appears as a first-line hypnotic in spite of its adverse effects common to phenothiazine (atropinic and antidopaminergic effects) and is a usefull medicine for the treatment of insomnia in psychotic patients.