Concordance of three approaches for operationalizing outcome definitions for multidrug-resistant TB.

BACKGROUND: The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).METHODS: Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.RESULTS: Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.CONCLUSION: High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.

Long term experience of felodipine in combination with beta-blockade and diuretics in refractory hypertension.

Felodipine, a new dihydropyridine, was given to 58 hypertensive patients in combination with an adrenergic beta-receptor antagonist and a diuretic agent. In all but 2 patients the blood pressure was unsatisfactorily controlled on standard triple therapy, i.e. alpha beta-blocker, a diuretic and a vasodilator. A 48-week follow-up was completed by 54 patients. After an initial dose titration period, the maintenance dose of felodipine was 5 mg twice daily in 14 patients and 10 mg twice daily in 34 patients. In the remaining 6 patients, the dose ranged from 5 mg every morning to 25 mg twice daily. The dosages of beta-blocking agent and diuretic were considerably reduced during the study period. Mean supine blood pressure was reduced from 170/101 mm Hg on triple therapy before felodipine to 145/86 mm Hg (p less than 0.001) after 2 weeks on felodipine. This improvement was sustained throughout the study and was measured at 144/86 mm Hg (p less than 0.001) after 48 weeks. There was no increase in resting heart rate and no orthostatic fall in blood pressure. Bodyweight was not increased and felodipine was generally well tolerated. Three patients were withdrawn owing to side effects and 1 was socially non-compliant. It is concluded that felodipine is a potent and well tolerated vasodilator, and will be useful in the long term combination treatment of previously refractory hypertension.

Acute and steady-state pharmacokinetics and antihypertensive effects of felodipine in patients with normal and impaired renal function.

Eighteen patients (14 men and 4 women, aged 36-74 years) treated with metoprolol for a month were included in the study. Twelve had impaired renal function (IRF) with a glomerular filtration rate (GFR) of 7.5-77.1 mL/min and six having normal renal function (NRF) with a GFR of 84.9-113.0 mL/min. Plasma and urine concentrations of felodipine and metabolites, heart rate, and blood pressure were recorded over 24 hours on day 1 after an oral dose of 10 mg felodipine and 0.04 mg 3H-felodipine IV and repeated on day 29 during continuous treatment with felodipine, 10 mg bid. The bioavailability of the oral dose on day 1 and day 29 was 13% and 12.5%, respectively. The terminal plasma half-life (t1/2) on day 29 was 22 hours and systemic clearance was 490 mL/min on day 1 and 434 mL/min on day 29 (NS). There were no differences in these parameters between NRF and IRF. The protein binding determined by equilibrium dialysis in the six patients with the lowest GFR was 99.74% on day 1 and 99.73% on day 29 and did not differ significantly from previously reported values in healthy subjects. The mean supine blood pressure before the acute dose of felodipine was 164/96 mm Hg in the IRF patients and 145/95 mm Hg in the NRF patients. A maximum decrease of 37/22 mm Hg and 32/19 mm Hg, respectively, was seen within 1.5 hours after dose and at 12 hours the reduction was 12/9 and 15/10 mm Hg, respectively, compared to baseline values. At steady state the morning blood pressure before dose was 152/87 mm Hg in the IRF patients and 129/86 mm Hg in the NRF patients. Similar maximum decreases and effects at 12 hours were seen after dose on day 29 as on day 1. Data on the effect on diastolic blood pressure and plasma felodipine concentrations were well fitted to the Emax model. The maximum reduction in diastolic blood pressure using this model was 27% and the plasma concentration leading to 50% of the maximum effect was 6.2 nmol/L. In conclusion, renal disease does not affect the pharmacokinetics of felodipine. The pharmacokinetic and pharmacodynamic effects of felodipine are not altered during steady state. The renal excretion of inactive metabolites is reduced in IRF. However, the accumulation of metabolites in the blood does not affect the protein binding or the clearance of felodipine. No dosage adjustment of felodipine seems to be necessary in patients with hypertension and renal impairment.

[Biliary hemorrhage due to a false aneurysm of the hepatic and gastroduodenal arteries (author's transl)]. / Hémobilies postopératoires par faux anévrisme de l'artère hépatique et de l'artère gastroduodénale.

Two cases of biliary hemorrhage due to false aneurysms are presented, one on an abnormal hepatic artery, the other on the gastroduodenal artery. Half of the cases of biliary hemorrhage have an intrahepatic etiology. Extrahepatic cases are equally divided between the main biliary duct and the gallbladder. Among the diagnostic investigations most authors agree on the choice of selective arteriography of the coeliac trunk. Controle of intrahepatic biliary bleeding can be obtained by partial hepatectomy or by ligation of the hepatic artery which is well tolerated. Treatment of extrahepatic bleeding is more diverse and takes into account both anatomical and surgical possibilities.

Is the brown shrimp Crangon crangon (L.) population of the Vaccarès lagoon (Camargue, France, Rhône delta) an annual population?

To study the population dynamics of Crangon crangon in the Vaccarès lagoon in the Camargue (Rhône delta), the age of brown shrimp was determined using the method of Tiews (1954). This method consists in counting the number of segments of the outer branch of the first antenna. This number is correlated with the number of moults already accomplished by the shrimp. The duration of the intermoult depends on water temperature. Adapting this model to our environmental data, we determined the age of the brown shrimp. Hatching of larvae occurs in the sea in May, and juveniles enter the lagoon from June to September. Our results showed that Crangon crangon in the Vaccarès lagoon reached sexual maturity between 6 and 11 months, and individuals are 1 year old when they leave the lagoon. A few adults from the previous year (1+) migrate back to the lagoon the following year, but these older individuals represent only a very small part of the population, and have only been observed occasionally. The Vaccarès brown shrimp population can therefore be considered as annual, in contrast to northern European populations.