Routine database registration of biological therapy increases the reporting of adverse events twentyfold in clinical practice. First results from the Danish Database (DANBIO).

OBJECTIVE: To present from the Danish Database for Biological Therapies in Rheumatology (DANBIO) the frequencies and types of adverse events as well as risk factors during treatment with biological agents in clinical practice. METHODS: Adverse events during the first 2 years of clinical use of biological agents in Denmark were reported to the nationwide DANBIO and compared to the mandatory reports to the Danish Medicines Agency. RESULTS: Almost 90% of the patients treated with biological agents were registered in the DANBIO, and the database picked up 20 times as many adverse events as the Danish Medicines Agency. Infections and hypersensitivity reactions were the most prevalent adverse events. Age, disease duration, and previous number of disease-modifying anti-rheumatic drugs (DMARDS) were found to be risk factors for bacterial infections. CONCLUSION: A routine-based Danish database for biological therapies covers approximately 90% of patients and improves the reporting of adverse events.

Application of interhemispheric index for transcranial Doppler sonography velocity measurements and evaluation of recording time.

BACKGROUND AND PURPOSE: To validate the reliability of transcranial Doppler sonography velocity measurements in clinical settings, assessment of the reproducibility of repeated bilateral simultaneous measurements and the optimal recording time is needed. Our hypothesis was that interhemispheric indices would prove more valid than the absolute velocity measurements usually applied. The potential interference between ultrasound beams in bilateral samplings also needs evaluation. METHODS: Thirty healthy volunteers were studied at rest within hours or with a 2-month interval between measurements. Absolute blood flow velocities and side-to-side indices between velocities obtained in the middle cerebral arteries were measured over a 30-second period by two independent examiners. The correlation coefficient (r) and the coefficients of variation of the difference between either absolute velocities (CV) or indices (CVi) were calculated. The beat-to-beat variation of the diastolic, systolic, and mean velocities was also recorded. For evaluation of ultrasound beam interference, measurements were performed with and without one probe unplugged. RESULTS: In the interobserver study in which measurements were repeated within hours, r = .92, CV = 8.8%, and CVi = 4.1%. In the intraobserver study in which measurements were repeated with a 2-month interval, r = .8, CV = 13.0%, and CVi = 7.3%. A recording time of 30 seconds reduced CVi to 2.6%, whereas for absolute velocities 5-second recordings produced an acceptable variation. There was no significant interference between bilaterally placed probes. CONCLUSIONS: The introduction of interhemispheric indices improve interobserver and intraobserver reproducibility by approximately 50%. We recommend use of the index in clinical settings in which unilateral velocity changes are expected. For measurement of an interhemispheric index, a recording time of 30 seconds is recommended, whereas 5-second measurement periods yield a sufficient estimate of absolute velocities.

Fosfomycin-ampicillin versus gentamicin-ampicillin in the treatment of critically ill patients with pneumonia.

Thirty-two patients with severe pneumonia (22 on assisted ventilation) were entered into a prospective randomised trial, in which fosfomycin plus ampicillin (17 patients) was compared with gentamicin plus ampicillin (15 patients). Treatment was either 4 g fosfomycin or 80 mg gentamicin every 8 h and 1 g ampicillin every 6 h. Complete or partial clinical success was attained in 94% (16/17) in the fosfomycin group and in 80% (12/15) in the gentamicin group. Bacteriological success was 87.5% with fosfomycin-ampicillin and 90% with gentamicin-ampicillin. An intermediary sensitive Klebsiella pneumoniae strain developed complete resistance in the fosfomycin group, and an in vitro sensitive Pseudomonas aeruginosa strain was resistant in vivo in the gentamicin group. Two of three patients in the fosfomycin group receiving the infusion through a peripheral vein developed thrombophlebitis. No other side-effects were observed. We conclude that fosfomycin is at least as effective as gentamicin. Since fosfomycin is widely atoxic and may be given in large doses, irrespective of kidney function, it is considered to have advantages over gentamicin in the combined therapy of pneumonia.

Pivmecillinam plus pivampicillin in urinary tract infections: a randomized, open comparison with co-trimoxazole in hospitalized patients.

The efficacy and tolerance of a fixed-dose combination of 200 mg pivmecillinam and 250 mg pivampicllin was compared with that of co-trimoxazole (800 mg sulphamethoxazole plus 160 mg trimethoprim) in 42 hospital in-patients with complicated urinary tract infections. Patients received a 10-day course of tablets of either agent twice daily. The infecting organisms, which were Enterobacteriaceae (79%) and enterococci (21%), were eradicated in 17(89%) of the 19 patients given co-trimoxazole and in all 23 subjects who received pivmecillinam/pivampicillin. Sixteen (89%) of the 18 symptomatic patients responded clinically to co-trimoxazole. Pivmecillinam/pivampicillin was effective in 19 (95%) of 20 patients with symptomatic infections. There was a fairly good correlation between the bacteriological and clinical responses. No serious side-effects were recorded and all patients completed the prescribed course of treatment.

Mecillinam in urinary tract infections and in septicaemia.

The clinical and bacteriological efficacy as well as the tolerance of mecillinam, a new beta-lactam antibiotic, administered parenterally in a dose of 40 mg/kg body weight, was investigated in 21 hospitalized patients with urinary tract infections or septicaemia. Success, defined as eradication of infecting organisms two to five days after treatment, was found in eight of 16 patients with urinary tract infections. Persistence of the original pathogen after treatment was seen in four patients, all with complicated urinary tract infection. Reinfection was seen in two patients, while the results were unevaluable in two cases. The five patients with septicaemia were all cured of their infection, this result being attributed solely to mecillinam in two cases, while a combined action of mecillinam and another antibiotic produced a cure in the other three cases. Escherichia coli resistant to mecillinam were isolated from two patients with persistence of bacteriuria following mecillinam treatment. Impairment of renal function may have been a contributory factor to the poor treatment response in patients with complicated urinary tract infection. Inasmuch as no important side-effects were recorded and mecillinam appears safe in patients with impaired renal and liver function, a higher dose may be indicated in these more complicated cases.