Variability in outpatient antimicrobial consumption in Israel.

BACKGROUND: Antibiotic consumption has an important effect on microbial resistance. Nationwide data on the comparative use of antibiotics in outpatient settings in Israel have only been partially collected and published. The aim of our study was to analyze the use of antibiotics in the outpatient setting in Israel and assess a number of influencing factors. MATERIALS AND METHODS: Defined daily doses per 1,000 inhabitants per day (DID) of total antibiotic use, consumption in different age groups, and consumption of different antibiotic groups were calculated for the years 2003-2005 in the districts of Israel. The data was collected from prescription data compiled by the pharmaceutical services of "Clalit Health Services", the largest health maintenance organization (HMO) in Israel, covering 55% of the population.Trends in use and variables associated with antibiotic consumption were analyzed. RESULTS: There was a significant decrease in antibiotic use from 2003 to 2005, ranging from 1.8 to 8.2% in the different districts. The highest consumption was noted in the youngest age groups, with more than half of all antibiotics prescribed to children < or = 18 years of age. Antibiotic consumption was significantly different between the different regions in Israel. A multivariate analysis revealed that a higher prevalence of diabetes mellitus was the only significant variable associated with antibiotic use. Variability in the use of different antibiotics was also found; for example, amoxicillin comprised 19.5-33.4% of total antibiotic consumption in the different districts, while fluoroquinolone consumption ranged from 3.2 to 7.3%. CONCLUSIONS: Outpatient antibiotic use in the population insured by "Clalit Health Services" declined between 2003 and 2005. Children had the highest consumption rates. There were large differences in antibiotic use between geographic regions, and diabetes mellitus was the only variable significantly associated with antibiotic use. We therefore conclude that most of the differences in antibiotic use are likely due to doctor preferences, local routines, and patients' attitudes and expectations.

A survey of primary care physicians' perceptions of their patients' use of complementary medicine.

PURPOSE: To study the perceptions and attitudes of primary care physicians concerning their patients' use of complementary medicine. METHODS: A questionnaire was distributed to all 165 primary care physicians attending a routine continuing-medicine education program. Items included physicians' estimated rates of patient utilization of complementary medicine or herbal remedies and of patient reportage of such use; physicians' knowledge about side effects and interactions of herbal remedies; and frequency with which physicians questioned their patients on the use of complementary medicine and herbal remedies. RESULTS: The compliance rate was 90.0% (n=150). Sixty-eight percent of physicians estimated that up to 15% of their patients use complementary medicine; 58% always or often asked their patients about it; 50% estimated that 10% of patients report use of complementary medicine, and 60% estimated the same rate for herbal remedies; 51% believed that herbal remedies have no or only mild side effects; more than 70% claimed that they had little or no knowledge about what herbal remedies are; 24% never referred patients for complementary medicine, and 69% did so occasionally. Twenty-five percent had some training in complementary medicine, and 31% practiced some kind of complementary medicine. Most of the physicians believed that people turn to alternative methods when they are dissatisfied with conventional medicine. CONCLUSIONS: Physicians underestimate the rate of complementary medicine use by patients, suggesting that many patients do not report such use to their physician. Since alternative treatments are potentially harmful and may interact with conventional medications, physicians should be encouraged to communicate with patients about complementary medicine in general and herbal remedies in particular, and they should regularly include questions about their use when taking histories. They should also inform themselves about risks of alternative treatments particularly with herbal remedies, and have access to appropriate information systems.

Influence of emulsion droplet surface charge on indomethacin ocular tissue distribution.

The aim of this study was to compare the corneal penetration of indomethacin from Indocollyre [a marketed hydro-poly(ethylene glycol) (PEG) ocular solution] to that of a negatively and a positively charged submicron emulsion. Male albino rabbits were separated randomly into three groups and each group (N = 15) was treated with either one drop of radiolabeled 0.1% Indocollyre, or 0.1% indomethacin positively or negatively charged submicron emulsion, respectively. The rabbits were sacrificed at selected time points and the eyes were enucleated. The eyes were dissected into the different tissues: cornea, conjunctiva, aqueous humor, iris, lens, vitreous, sclera, and retina. The samples were weighed before radioactivity counting. Regardless of the preparation instilled, the highest concentration of indomethacin was achieved in the cornea followed by conjunctiva, sclera retina, and aqueous humor. However, the positively charged emulsion provided significantly higher drug levels than the control solution and negatively charged emulsion only in the aqueous humor and sclera-retina. Furthermore, the spreading coefficient of the positively charged emulsion on cornea is four times higher than that of the negatively charged emulsion. It was therefore deduced that the positively charged submicron emulsions have better wettability properties on the cornea compared to either saline or the negatively charged emulsion. The positive charge may prolong the residence time of the drop on the epithelial layer of the cornea and thus enable better drug penetration through the cornea to the internal tissues of the eye, as confirmed by the animal studies.

Evaluation of a positively charged submicron emulsion of piroxicam on the rabbit corneum healing process following alkali burn.

The effect of piroxicam in three different formulations was tested on rabbits for 28 days in an alkali burn model. The ulceration healing process was determined by evaluating the severity of the burn (scored from 0 to 5), and the re-epithelization healing process was measured by the area of the defects. The results indicated that the piroxicam positively charged submicron emulsion was the most effective formulation in lowering the ulcerative cornea score while the piroxicam positively charged emulsion and the blank emulsion were more effective in promoting the re-epithelization healing process. The piroxicam solution elicited the slowest healing re-epithelization rate after 28 days and was unable to complete the entire healing process. The new positively charged submicron emulsion formulation of piroxicam had a pronounced effect on both the ulceration rate and epithelial defects in the management of corneal alkali-burning.

Physicochemical characterization and acute toxicity evaluation of a positively-charged submicron emulsion vehicle.

Fine, homogeneous, positively-charged emulsions with a mean droplet size of 138 +/- 71 nm and a zeta potential value of 41.06 mV were prepared using a combination of emulsifiers comprising phospholipids, poloxamer 188, and stearylamine. The pH of these emulsions decreased with time. However, the extent of decrease was dependent on the storage temperature. The mean droplet size of the emulsions that had been prepared with 1% poloxamer began to increase slightly after six months' storage, particularly when stored at 23 and 37 degrees C. However, emulsions prepared with 2% poloxamer remained stable for at least 10 months at 4 degrees C, suggesting that the poloxamer 188 concentration is critical for prolonged emulsion stability. The results of the ocular tolerance study in rabbit eye indicate that hourly administration of a positively-charged emulsion vehicle was well tolerated without any toxic or inflammatory response to the ocular surface during the five days of the study. Scanning electron microscopy revealed a normal corneal surface, which was not different from that of the animals treated with physiological saline. No marked acute toxicity was observed when 0.6 mL of positively-charged emulsion was injected intravenously to BALB/c mice. Furthermore, no difference was noted between this group of animals and the group injected with the marketed Intralipid emulsion. These results were further confirmed in a rat study where there were no deaths following intravenous injection of 3.3 mL per rat of the positively-charged emulsion or Intralipid. Neither emulsion elicited any hepatotoxic or nephrotoxic effects. The overall results suggest that the novel positively-charged emulsion is suitable for parenteral use, and for ocular application.

Endocarditis and ventricular septal defect: surgical vs. conservative treatment.

Three patients with ventricular septal defect and bacterial endocarditis are reported. Because of the very frequent spontaneous closure of the defect, especially in children, and the rarity and benign nature of bacterial endocarditis superimposed on ventricular septal defect, it is suggested that the condition be treated conservatively. An exception to this is the rare case with recurrent endocarditis, mainly in older individuals, in whom surgery may be contemplated.