Colchicine: a simple and effective treatment for pericarditis in systemic lupus erythematosus? A report of 10 cases.

OBJECTIVES: Pericardial involvement is a frequent manifestation of systemic lupus erythematosus (SLE). Growing evidence suggests that colchicine may be useful for acute or recurrent pericarditis. We report for the first time a series of 10 consecutive cases of SLE with pericarditis treated with colchicine. METHODS: Inclusion criteria in this retrospective study were diagnosis of SLE, pericarditis and receiving colchicine. RESULTS: We included 10 consecutive cases of SLE with pericarditis treated with colchicine (nine women, mean age at the index pericarditis 35 ± 12 years). Pericarditis was the initial manifestation of SLE for two patients, whereas eight patients had SLE lasting for a median of 2.5 years (15 days to 13 years) and had received prednisone (n = 7, 2-30 mg/d), hydroxychloroquine (n = 7), azathioprine (n = 3), methotrexate (n = 2), and mycophenolate mofetil (n = 1). For six patients, pericarditis was associated with other SLE manifestations. Altogether, colchicine avoided the use (n = 2) or increase in dosage (n = 5) of steroids in seven cases; the increase in steroids dosage was minimal for two patients. Colchicine 1 mg was given for a median of 39 days (10 days to 54 months). Symptoms completely resolved after a median of 2.5 days (1-30 days) after initiation of colchicine. Colchicine was maintained or resumed in six patients to prevent recurrence, with no further relapse. CONCLUSIONS: Colchicine may be safe and effective in treating SLE pericarditis and used as a steroids-sparing agent. These preliminary results need to be confirmed in a larger study with longer follow-up.

Tobacco differentially affects the clinical-biological phenotypes of ANCA-associated vasculitides.

OBJECTIVES: To describe the clinical-biological phenotype of ANCA-associated vasculitides (AAV) according to tobacco consumption. METHODS: We conducted a descriptive study to describe that phenotype at diagnosis according to tobacco use. AAV patients entered in the French Vasculitis Study Group database with data on smoking habits were analysed. The clinical-biological phenotypes at diagnosis were compared according to current tobacco use (current smokers) or not (including previous and never smokers). RESULTS: AAV diagnoses were: granulomatosis with polyangiitis (GPA) for 583 (50%), eosinophilic granulomatosis with polyangiitis (EGPA) for 326 (28%) and microscopic polyangiitis (MPA) for 256 (22%). Among them, 973 patients (84%) never smoked, 116 (10%) were previous smokers and only 76 (6%) were current smokers. Current smokers were younger age (p=0.01), male gender (p=0.004), less frequently EGPA (p=0.017) and MPA (p=0.036), and had less frequent kidney involvement (p=0.10). Among GPA patients, current smokers, compared to non-current smokers, were younger age (p=0.02), male gender (p=0.08), more frequent skin involvement (p=0.03) and less frequent ENT involvement (p=0.06). Among EGPA patients, current smokers, compared to non-current smokers, were also younger (p=0.028) and had less frequent constitutional symptoms (p=0.02), arthralgias (p=0.04), renal involvement (p=0.025) and MPO-ANCA (p=0.02). Finally, analysis of MPA patients was impossible because only 6 (2%) were current smokers. CONCLUSIONS: These results suggest that tobacco use could differentially affect GPA and EGPA clinical-biological phenotypes, and support the role of environmental exposures in AAV development and its phenotype.

Insulin glargine and risk of cancer: a cohort study in the French National Healthcare Insurance Database.

AIMS/HYPOTHESIS: Using the Echantillon Généraliste de Bénéficiaires: random 1/97 permanent sample of the French national healthcare insurance system database (EGB), we investigated whether, as previously suspected, the risk of cancer in insulin glargine (A21Gly,B31Arg,B32Arg human insulin) users is higher than in human insulin users. The investigation period was from 1 January 2003 to 30 June 2010. METHODS: We used Cox proportional hazards time-dependent models that were stratified on propensity score quartiles for use of insulin glargine vs human insulin, and adjusted for insulin, biguanide and sulfonylurea possession rates to assess the risk of cancer or death in all or incident exclusive or predominant (≥ 80% use time) users of insulin glargine compared with equivalent human insulin users. RESULTS: Only type 2 diabetic patients were studied. Exposure rates varied from 2,273 and 614 patient-years for incident exclusive users of insulin glargine or human insulin, respectively, to 3125 and 2341 patient-years for all patients predominantly using insulin glargine or human insulin, respectively. All-type cancer HRs with insulin glargine vs human insulin ranged from 0.59 (95% CI 0.28, 1.25) in incident exclusive users to 0.58 (95% CI 0.34, 1.01) in all predominant users. Cancer risk increased with exposure to insulin or sulfonylureas in these patients. Adjusted HRs for death or cancer associated with insulin glargine compared with human insulin ranged from 0.58 (95% CI 0.32, 1.06) to 0.56 (95% CI 0.36, 0.87). CONCLUSIONS/INTERPRETATION: There was no excess risk of cancer in type 2 diabetic patients on insulin glargine alone compared with those on human insulin alone. The overall risk of death or cancer in patients on insulin glargine was about half that of patients on human insulin, thereby excluding a competitive risk bias.

[Contribution and limits of "OSCE", "long-case" and "global end-of-placement marking" as end-of-rotation assessment methods. Experience from two internal medicine wards]. / Apport et limites des « ECOS ¼, « examen clinique au lit du malade ¼ et « appréciation globale de stage ¼ comme modalité d'évaluation de fin de stage. Expérience de deux services de médecine interne.

INTRODUCTION: During placements, there is an opportunity to learn clinical skills and to assess their application. However, it represents two different goals. The validity of an end-of-placement assessment is questionable, as the medical competency is contextual. We decided to evaluate the contribution and limits of different assessment modalities as an end-of-placement assessment. MATERIAL AND METHODS: Internal medicine clerks were assessed using the Mini-Cex grid by a structured objective clinical examination (OSCE), a long-case clinical examination (LCE) and a global end-of-placement marking (GEPM). Following these evaluations, students and teachers fulfilled an open questionnaire. RESULTS: In 2021, 41 students and 16 teachers participated in the study. Physical examination was evaluated in 0%, 97% et 76% of cases during OSCE, LCE and GEPM, respectively; teaching skills were assessed for 100, 42 et 49% of students in OSCE, LCE and GEPM, respectively. As compared to OSCE, there was a perceived superiority of LCE regarding its formative value (P=0.07 and P=0.03) and its summative value (P=0.0007 and P=0.02), for students and teachers, respectively. Qualitative analysis highlights the breadth of clinical skills that could be assessed during OSCE stations. Integration into a team was an additional skill that could specifically be assessed during GEPM. GEPM could also take into account the progress made during placement. CONCLUSION: Despite its subjectivity, LCE seemed to be the preferred modality for an end-of-rotation assessment.

Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP).

OBJECTIVE: To explore whether sertindole increases all-cause mortality or cardiac events requiring hospitalization, compared with risperidone. METHOD: Multinational randomized, open-label, parallel-group study, with blinded classification of outcomes, in 9858 patients with schizophrenia. RESULTS: After 14147 person-years, there was no effect of treatment on overall mortality (sertindole 64, risperidone 61 deaths, Hazard Ratio (HR) = 1.12 (90% CI: 0.83, 1.50)) or cardiac events requiring hospitalization [sertindole 10, risperidone 6, HR = 1.73 (95% CI: 0.63, 4.78)]: Of these, four were considered arrhythmia-related (three sertindole, one risperidone). Cardiac mortality was higher with sertindole (Independent Safety Committee (ISC): 31 vs. 12, HR=2.84 (95% CI: 1.45, 5.55), P = 0.0022; Investigators 17 vs. 8, HR=2.13 (95% CI: 0.91, 4.98), P = 0.081). There was no significant difference in completed suicide, but fewer sertindole recipients attempted suicide (ISC: 68 vs. 78, HR=0.93 (95% CI: 0.66, 1.29), P = 0.65; Investigators: 43 vs. 65, HR=0.67 (95% CI: 0.45, 0.99), P = 0.044). CONCLUSION: Sertindole did not increase all-cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole.

[Association between psychiatric comorbidities and hospital length of stay in post-emergency internal medicine patients]. / Association des comorbidités psychiatriques avec la durée de séjour des patients en médecine interne d'aval des urgences.

INTRODUCTION: Patients with psychiatric disorders suffer from a higher rate of somatic disorders than those without psychiatric disorder, often inappropriately managed. Our study aimed to describe patients with psychiatric comorbidity in post-emergency internal medicine units and to compare their length of hospital stay to patients without psychiatric disease. METHODS: This French cross sectional study used the data warehouse of the greater Paris hospitals. It included, all patients hospitalized through the emergency department in 9 internal medicine departments during the year 2017. Psychiatric disorders and the burden of somatic disorders (Charlson score) were determined through diagnostic coding. Charlson score and hospital length of stay were compared between patients with and without psychiatric comorbidity. RESULTS: In total, 8981 hospital stays (8001 patients) were included, 1867 (21%) with psychiatric comorbidity. After adjusting for age, gender, hospital and main diagnosis, the Charlson score was on average 0.68 higher in the psychiatric comorbidity group (P<0.001) and the length of hospital stay was 30% higher after further adjustment on the Charlson score (P<0.001). These differences were consistent for each main diagnosis. CONCLUSION: Patients with psychiatric comorbidity are frequent in post-emergency internal medicine wards. They experience longer hospital stays, only partly related with a higher burden of somatic disorders. Special attention should be paid to this vulnerable population.

Infective endocarditis due to Citrobacter koseri in an immunocompetent adult.

Citrobacter koseri (formerly Citrobacter diversus) is a motile gram-negative bacillus usually arising from urinary and gastrointestinal tracts. C. koseri rarely causes infection in immunocompetent patients and, thus far, has been considered an opportunistic pathogen. We report on a 30-year-old man, with no medical past, hospitalized for infective aortic endocarditis due to C. koseri. Four weeks of antibiotherapy led to a full recovery for this patient. However, this case is unusual, as previous history and 1 year of follow-up showed no features of intercurrent immunosuppression. Microbiological diagnosis was based on using 16S rRNA gene sequencing.

[Reliability and validity of a workbook for assessment of professional competencies of internal medicine residents]. / Évaluation multicentrique de la reproductibilité et de la validité d'un carnet d'évaluation des compétences professionnelles des internes de médecine interne.

INTRODUCTION: Though several assessment tools for resident professional skills based on workplace direct observation have been validated, they remain scarcely used in France. The objective of this study was to evaluate the reliability and the validity of a workbook including several assessment forms for different components of the professional competency. METHODS: Three assessment forms have been tested over a period of 6 months in a multicentric study including 12 French internal medicine departments: the French version of the mini-CEX, an interpersonal skills assessment form (OD_CR) and the multisource feedback form (E_360). Reliability has been assess using the intra-class correlation coefficient (ICC) and the Cronbach alpha coefficient. Arguments for validity have been provided looking at the ability of the forms to detect an increase in the scores over time and according to the level of experience of the resident. RESULTS: Twenty-five residents have been included. The Cronbach alpha was of 0.90 (n=70) with the mini-CEX, 0.89 with the OD_CR (n=62) and 0.77 with the E_360 (n=86). ICC showed a wide variation according to the items of the mini-CEX and the OD-CR probably due to the poor number of observations performed by residents. The scores of most of the items of these two forms increased between M1 and M6. The scores of the E_360 were high: 7.3±0.8 to 8.3±2.4 (maximum 9) and did not vary according to the level of experience. CONCLUSION: This study suggest that it would be difficult to ensure a sufficient reliability for professional skills assessment using these tools given our available current human and material resources. However, these assessment forms could be added to the resident portfolio as supports for the debriefing in order to document their progression during their formation.

Is there any evidence to support the use of anti-depressants in painful rheumatological conditions? Systematic review of pharmacological and clinical studies.

The aim of this study was to review the evidence supporting the use of anti-depressants in painful rheumatological conditions. A systematic review of papers published between 1966 and 2007, in five European languages, on anti-depressants in rheumatological conditions was performed. Papers were scored using Jadad method and analgesic ES was calculated. We selected 78 clinical studies and 12 meta-analyses, from 140 papers. The strongest evidence of an analgesic effect of anti-depressants has been obtained for fibromyalgia. A weak analgesic effect is observed for chronic low back pain, with an efficacy level close to that of analgesics. In RA and AS, there is no analgesic effect of anti-depressants, but these drugs may help to manage fatigue and sleep disorders. There is no clear evidence of an analgesic effect inOA, but studies have poor methodological quality. Analgesic effects of anti-depressants are independent of their anti-depressant effects. Tricyclic anti-depressants (TCAs), even at low doses, have analgesic effects equivalent to those of serotonin and noradrenalin reuptake inhibitors (SNRIs), but are less well tolerated. Selective serotonin reuptake inhibitors (SSRIs) have modest analgesic effects, but higher doses are required to achieve analgesia. Anti-depressant drugs, particularly TCAs and SNRIs, have analgesic effects in chronic rheumatic painful states in which analgesics and NSAIDs are not very efficient, such as fibromyalgia and chronic low back pain. In inflammatory rheumatic diseases, anti-depressants may be useful for managing fatigue and sleep disorders. Further studies are required to compare anti-depressants with other analgesics in the management of chronic painful rheumatological conditions.

[Headaches and migraines]. / Céphalées et migraine.

A 2004 update of the International Headache Society classification refined the diagnostic criteria for headaches, the most frequent of which remain tension headaches and migraines. Diagnosis remains essentially clinical, while complementary neuroimaging tests are done on an on-request basis for newly appearing headaches or for changes in migraine episodes. Given the topographies of migraines and tension headaches, when their characteristics are atypical, the otolaryngological hypothesis is often suggested. If in doubt, a test treatment with triptans can be attempted.

Systemic effects of three beta-blocker eyedrops: comparison in healthy volunteers of beta 1- and beta 2-adrenoreceptor inhibition.

The beta 1- and beta 2-adrenoreceptor blockade by means of the systemic diffusion of three beta-blocker eyedrops--timolol, carteolol, and betaxolol--was evaluated in a randomized, single-blind, three-way crossover study in 18 volunteers. The blockade was evaluated by analyzing the variations of the beta 1- and beta 2-blockade effects of isoproterenol before and after instillation of one drop in each eye. The beta 1-blockade effect was judged on the variation of heart rate, and the beta 2-blockade effect was judged on the change in peripheral blood flow measured by veno-occlusive plethysmography. Comparison of the blockade by these drops showed that carteolol and timolol totally inhibited the beta 1 and beta 2 effects of a dose of isoproterenol able to increase heart rate by 50% (placebo eyedrops were used as a control). Betaxolol differ significantly because it allowed the same effects with the same dose of isoproterenol. Intensity of the blockade was measured by comparison of the effective doses of isoproterenol. Carteolol and timolol were shown to be four times more inhibitory.

Rizatriptan in the treatment of menstrual migraine.

OBJECTIVE: To determine the efficacy of oral rizatriptan 10 mg and 5 mg for treating menstrually associated migraine attacks. METHODS: Data from two large clinical trials with identical designs were included in a retrospective analysis. The studies were randomized, double-masked, placebo-controlled, incomplete block, two-period, crossover designs. Women with migraines were randomly assigned to one of five treatment sequences for the treatment of two migraine attacks. Only data from the first attack in women with migraines who were treated with rizatriptan or placebo were included in the analysis. A menstrually associated attack was defined as one that occurred within 3 days before or after the onset of the last menstrual period. RESULTS: In the subgroup of 335 women with menstrually associated migraine, rizatriptan was effective compared with placebo. At 2 hours after dosing, 68% of 139 women taking rizatriptan 10 mg and 70% of 115 women taking rizatriptan 5 mg with a menstrually associated migraine had pain relief compared with 44% of 81 patients taking placebo (P <.05). In all women, rizatriptan was as effective in treating menstrual as well as nonmenstrual migraine: 68% of 139 patients taking rizatriptan 10 mg with a menstrually associated migraine had pain relief at 2 hours after dosing compared with 69% of 393 patients with nonmenstrually associated attacks (test of menstrual association = nonsignificant; the analysis had 80% power to detect a difference of six percentage points between groups). Similar results were found for rizatriptan 5 mg (menstrual = 70%, nonmenstrual = 66%; not statistically significant). CONCLUSION: Rizatriptan is effective in the treatment of menstrually associated migraine attacks.

Systemic and local tolerability of ophthalmic drug formulations. An update.

All eye drops raise problems of local tolerance, but with variable frequencies. They can induce pain on instillation, allergic reactions, delayed healing, punctate keratitis, disturbances of lacrimal secretion, disturbances of accommodation (especially the parasympathomimetics) and local pigmentation after prolonged use. Corticosteroids are associated with 2 major risks: chronic glaucoma and cataract, initially reversible if treatment is stopped. There is still a major risk of corneal herpes with corticosteroids. It is important to be aware of these local problems as they are responsible for poor patient compliance. The systemic effects essentially concern the agonists and antagonists of the autonomic nervous system. beta-Blocker eye drops can cause bronchospasm, heart failure, syncope and psychiatric disorders, especially at high doses and with nonselective beta-blockers. These consequences are usually related to failure to comply with the prescribing precautions. alpha-Adrenergic agonists, which exert dose-dependent effects, can induce hypertensive crises or angina attacks. Apart from patients at risk (children under the age of 30 months and the elderly), parasympathomimetics cause few systemic adverse effects; anticholinesterases, which have curare-like properties, are contraindicated for 6 weeks before general anesthesia. In the very young and the very old, atropinic eye drops carry a risk of cardiovascular collapse and neuropsychiatric disturbances. Problems may also occur with other classes of drugs such as anti-infectives, antispectics, anti-inflammatories and contact lens products. Nevertheless, it is clear that this form of treatment is generally very well tolerated in relation to the volume of eye drops prescribed by ophthalmologists each day.

Bronchial and cardiovascular effects of ocular topical B-antagonists in asthmatic subjects: comparison of timolol, carteolol, and metipranolol.

B antagonists eye drops are most effective for the treatment of chronic open angle glaucoma. By this way of administration they have a very good systemic bioavailability. Bronchial, and cardiovascular effects of three of these topicals: timolol, carteolol and metipranolol have been evaluated in three parallel groups of asthmatic patients. The three topics induce bronchoconstriction without significant difference between them, and lower heart rate (sometimes very intensely) whatever the B antagonist studied. From these data, it is recommended to practitioners to follow carefully the rules of administration of B blockers, even in eye drops.

Dizziness in the elderly and calcium channel antagonists.

Because of the benefit-risk ratio in their favor, calcium channel antagonists are considered to be a safe form of treatment of hypertension in the elderly. However, the outcome of dizziness in some patients over 65 yr old during the first few days of treatment with these drugs has to be considered. Five cases of "malaise" have been mentioned, which occurred during the first few days of treatment. The imputability of the drug in question has been evaluated. Additional factors have been found, ie orthostatic hypotension whatever its mechanism, and association with diuretics, with or without hyponatremia. The above-mentioned cases led to a study in 10 supine elderly women (mean age 85 +/- 3 yr) with normal blood pressure. In this study, systolic and diastolic blood pressure were monitored after a 20-mg oral dose of nicardipine for 3 h. Even in the supine position, a significant fall in blood pressure was observed as early as the 15th min after administration, which could be significant, occasionally reaching 45% of the initial value. Before administering a calcium channel antagonist to an elderly person, orthostatic hypotension has to be investigated. Association with a diuretic results in high risk due to hypovolemia that can enhance the vasodilatory effect of calcium antagonists.

Comparison of propranolol and sotalol pharmacokinetics in obese subjects.

Six obese subjects (mean +/- s.d. : 145.1 +/- 16.7% of ideal body weight) were randomly assigned to a single i.v. dose either of (+/-)-propranolol base (0.108 mg kg-1 of ideal body weight) or of (+/-)-sotalol base (1.06 mg kg-1 of ideal body weight). Each subject received the other drug 7 days later. Pharmacokinetic parameters were compared with those obtained previously in non-obese control subjects. In obese subjects, the pharmacokinetic data calculated for sotalol were comparable with those measured in controls (total body clearance = 9.4 +/- 2.9 L h-1; volume of distribution during the terminal phase = 79.8 +/- 19.8 L or 0.9 +/- 0.2 L kg-1; terminal half-life = 6.2 +/- 1.6 h). For propranolol, total clearance (44.3 +/- 15.9 L h-1) and volume of distribution (230.5 +/- 48.2 L or 2.7 +/- 0.7 L kg-1) were significantly less than control values. The terminal half-life (3.9 +/- 1.1 h), was not significantly increased. These results could be explained by altered tissue blood flow and a decreased metabolic capacity of the liver in obese subjects.

[Drug interactions and the elderly]. / Interactions médicamenteuses et personnes agées.

Elderly people are particularly at risk for drug interactions, for several reasons. They are the part of the population who consume the most drugs: over 75 years the mean number of drugs on a prescription is 5.6. As they suffer from various associated diseases, they see several medical specialists, each of them adding a new prescription to the others. Self-prescriptions complicate the problem because they are rarely mentioned. Changes in pharmacokinetics in the elderly tend to increase blood concentrations of drugs. Elderly people suffer from altered homeostatic mechanisms to compensate for adverse drug effects. As a whole, such individuals are more exposed to the side effects of drugs. The drugs most often involved in these interactions are diuretics, non-steroidal anti-inflammatory drugs, benzodiazepines, antiarrhythmics, cardiac glycosides, antihypertensive drugs, oral antidiabetics and antalgics. The clinical accidents most often occurring with these drug interactions are: malaise, orthostatic hypotension, loss of conciousness, amnesia, confusion, renal insufficiency, digestive problems. Since elderly people are less likely to recover easily, this problem of drug interaction should be looked for systematically.

[Use of calcium inhibitors excluding cardiac pathology and arterial hypertension]. / Utilisation des inhibiteurs des transferts calciques en dehors de la pathologie cardiaque et de l'hypertension artérielle.

Many studies have been done to try to define new therapeutic uses for calcium antagonists, in diseases in which calcium plays a role. Positive results have been obtained in the prevention of acute attacks of idiopathic Raynaud's disease and migraine, and in effort-induced asthma. Some activity could be demonstrated in selected groups of patients with pulmonary hypertension, manic-depressive illness, untractable epilepsy, various functional gynecological or digestive disorders, and in drug-induced nephrotoxicity. A possible effect on the prevention of resistance to anti-cancer drugs could be of major interest. Their antiplatelet effect, and their possible effect against atherosclerosis, which remains to be confirmed, their lack of side-effects in asthmatics and of interference with glucose regulation increase their usefulness in patients with hypertension or ischemic heart disease, especially when other diseases are present.

[Identification, during development, of a methodology targeted at determining the positioning of new drugs for therapeutic strategies: examples of rheumatoid arthritis and cardiac insufficiency]. / Identification, lors du développement, d'une méthodologie pour déterminer la place des nouveaux médicaments dans les stratégies thérapeutiques: exemples de la polyarthrite rhumatoïde et de l'insuffisance cardiaque.

The Marketing Authorization (MA) granted to a new molecular entity does not allow for proper anticipation of its future positioning within the therapeutic strategy. A specific methodology should be devised as early as during the pre-MA development phase that could result in an initial positioning that should be subjected to further reappraisal with regard to scientific advances, the arrival of new treatments and further developments with this molecule. A methodology is thus proposed, based on early optimisation of the development plan, the granting of subsequent MAs, and reappraisal of the positioning within the strategy, based on analysis of all available data. It should be possible to take into account the economic context, within an agreed system with pre-defined medico-economic criteria. This may in turn raise the issue of the role of the various parties involved in this assessment, as well as how to understand the respective opinions of stakeholders: authorities, sponsors, prescribers and patients, each of whom has a specific view of the definition of the strategic objective that should apply to the disease concerned.