Systemic juvenile idiopathic arthritis in French Afro-Caribbean children, a retrospective cohort study.

INTRODUCTION: The epidemiology and clinical presentation of systemic juvenile idiopathic arthritis (sJIA) in the Afro-Caribbean population is not well described. METHODS: Retrospective study conducted between January 2000 and January 2022 in the French Overseas Departments of America. Clinical data were obtained from multiple sources: computerized hospital archives, registries of referring pediatricians, and the French National Registry for rare diseases. The disease studied was sJIA defined according to international criteria. RESULTS: Twenty-five patients were identified. Mean age at diagnosis was 7.5 years (range: 1.2-14.9 years) and mean duration of follow-up was 5.2 years (range: 0.5-16 years). All patients had joint involvement at diagnosis with 68% presenting inflammatory arthritis and 32% inflammatory joint pain. Sixteen percent had coronary involvement at onset. More than half (52%) suffered from macrophage activation syndrome (MAS) during childhood (32% at onset). The mean number of flares in childhood was 2 (Range: 1-5). Sixty-eight percent of patients had disease control during childhood without biotherapy. The most frequent second line treatment was anakinra (7/8). There was no difference in clinical or biological severity according to gender. The median duration of treatment during childhood was 5 months (range: 2-144) and 72% had a cumulative treatment duration of less than one year. CONCLUSION: These patients of Afro-Caribbean origin suffering from sJIA showed some specificities, such as a higher rate of MAS and coronary involvement at onset. The incidence per year was stable over a 20-year period. Overall outcomes during childhood were similar to western countries.

Chikungunya disease among infants in French West Indies during the 2014 outbreak.

BACKGROUND: We aimed to describe the clinical and laboratory features of Chikungunya disease in infants aged from 1 month to 2years. METHODS: This epidemiologic study was carried out at the Pointe-à-Pitre University Hospital from May to September 2014. We collected data prospectively from infants hospitalized for Chikungunya disease. RESULTS: A total of 154 infants were included. Hyperthermia was greater than 38.5°C the first 48h and during on average 2.7 days. Pain (on mobilization and/or cutaneous hyperesthesia and/or arthralgia) was present in 82% of the cases. Loss of appetite was reported for 62% of the infants. Initial maculopapular erythematous eruption occurred in 69% of the cases. A vesiculobullous eruption was secondarily observed in 7% of the cases. Edema on the feet and/or hands was present in 48% of the cases. Febrile seizure was observed in 12% of the cases. Lymphopenia was the most frequent laboratory finding, present in 94% of the infants. No cases of thrombocytopenia were observed. The reported complications were: bullous epidermolysis, state of epilepticus, and severe acute hepatitis. CONCLUSION: This study highlights a suggestive clinical presentation of Chikungunya diseases combining pain, fever, tachycardia, foot and/or hand edema. Lymphopenia, monocytosis, and the absence of thrombocytopenia were relevant biological signs.

Pharmacokinetics of ornidazole in patients with severe liver cirrhosis.

Pharmacokinetics of ornidazole, a nitroimidazole derivative, was studied after intravenous injection in 10 patients with severe alcoholic cirrhosis and 10 healthy volunteers. Plasma concentrations of ornidazole and its two major hydroxylated metabolites, M1 (alpha-(chloromethyl)-2-hydroxymethyl-5-nitroimidazole-1-ethanol) and M4 (3-(2-methyl-5-nitroimidazole 1-yl) 1,2 propane diol), were measured by HPLC. The t1/2 of ornidazole was 14.1 +/- 0.5 hours for normal subjects and 21.9 +/- 2.9 hours for patients with cirrhosis. Mean plasma clearance was 50.6 +/- 2.1 ml/min in control subjects and 34.9 +/- 4.9 ml/min in patients, whereas apparent V SS was not modified in hepatic insufficiency. In healthy volunteers, M1 and M4 levels are well below levels of the parent drug; in cirrhosis both metabolites accumulate in plasma as a result of decreased elimination. Hepatic cirrhosis prolongs ornidazole elimination, and to avoid cumulation the interval between repeated doses could be doubled.

Effect of mechanical ventilation on hepatic drug pharmacokinetics.

Mechanical ventilation was able to induce a decrease in cardiac output and regional blood flow, especially hepatic flow. Thus, hepatic elimination of drugs with a high hepatic-extraction ratio, which was linked to alteration in hepatic blood flow, could be reduced during mechanical ventilation. The aim of this work was to determine the effect of mechanical ventilation on pharmacokinetic parameters of lidocaine, which is a well-known nonrestrictive elimination drug at the hepatic level. Five patients (mean age, 58 years) with normal hepatic function and quite similar gasometric parameters before and after weaning from mechanical ventilation were studied. With a washout period of 48 hours between mechanical ventilation and spontaneous ventilation, each patient was submitted to the following protocol: lidocaine in a bolus (1.5 mg/kg intravenously), followed by infusion (1.0 to 1.7 mg/min for 120 minutes). The results were that the peak plasma concentration after the bolus during mechanical ventilation was 3.22 +/- 0.37 mg/L (mean +/- SE) vs 2.40 +/- 0.35 mg/L during spontaneous ventilation (p less than 0.02). Steady-state plasma concentration during mechanical ventilation was 2.10 +/- 0.20 mg/L vs 1.64 +/- 0.16 mg/L during spontaneous ventilation (p less than 0.01). Total clearance was 604.2 +/- 87.0 ml/min during mechanical ventilation vs 775.0 +/- 112.1 ml/min during spontaneous ventilation (p less than 0.01). Elimination half-life was 245.2 +/- 50.6 minutes during mechanical ventilation vs 160.0 +/- 40.6 minutes during spontaneous ventilation (p less than 0.05). Distribution volume was 188.6 +/- 50.2 L during mechanical ventilation and 183.0 +/- 50.8 L during spontaneous ventilation (not significant). These preliminary data clearly demonstrated a decrease in lidocaine elimination in patients submitted to mechanical ventilation, but the magnitude of dosage adjustment of such a highly hepatic-extracted drug in patients submitted to mechanical ventilation remains to be investigated.

Entrapment of the suprascapular nerve.

Operative release for entrapment of the suprascapular nerve was carried out in 35 patients. They were assessed at an average of 30 months (12 to 98) after operation using the functional shoulder score devised by Constant and Murley. The average age at the time of surgery was 40 years (17 to 67). Entrapment was due to injury in ten patients and no cause was found in three; 34 had diffuse posterolateral shoulder pain. The strength of abduction was reduced in all the patients. The average Constant score, unadjusted for age or gender, before operative release was 47% (28 to 53). In 25 of the patients both the supraspinatus and infraspinatus muscles were atrophied and seven had isolated atrophy of the infraspinatus muscle. The average conduction time from Erb's point to the supraspinatus muscle and to the infraspinatus muscle was 5.7 ms (2.8 to 12.8) and 7.4 ms (3.4 to 13.4), respectively. In two patients MRI revealed a ganglion in the infraspinatus fossa and, in another, a complete rupture of the rotator cuff. The average time from the onset of symptoms to operation was ten months (3 to 36). A posterior approach was advocated. The average Constant score, after operative release, unadjusted for age or gender was 77% (35 to 91). The overall result was excellent in ten of the patients, very good in seven, good in 14, fair in two, and poor in two. The symptomatic and functional outcome in our series confirmed the usefulness and safety of operative decompression for entrapment of the suprascapular nerve.

Problems in therapeutic drug monitoring: free drug level monitoring.

Historically, it has been assumed that only free drug concentration is the pharmacologically active species. This article reviews the theoretical pharmacological and pharmacokinetic justifications for monitoring free drug levels. The determinants likely to influence plasma protein binding and the free concentrations of drugs are delineated. The different methods which can be used for determining free drug level are presented. Their advantages and drawbacks as well as their reliability and suitability for routine clinical practice are discussed. Currently, antiepileptic drugs such as valproic acid, phenytoin, carbamazepine and a few antiarrhythmic drugs meet the theoretical criteria justifying free drug level monitoring. Conditions causing alteration in free concentrations of these drugs are reported. But, for all these drugs, there is a considerable lack of data establishing the correlations between therapeutic or toxic response and free concentration. Presently, our capability to interpret correctly the free drug level data is still limited. In the future, much more effort must be devoted in order to provide sufficient information on the clinical relevance of free drug concentration.