Community-Based Approach to Promote Rational Use of Antibiotics in Indonesia: The Development and Assessment of an Education Program for Cadres.

BACKGROUND: Cadres play an important part in providing community-based education. This study developed and assessed an education program for cadres in Malang, Indonesia, as 'change agents' to promote rational antibiotic use. METHODS: In-depth-interviews with stakeholders (N = 55) and a subsequent group discussion with key personnel (N = 5) were conducted to develop a relevant education tool for cadres. This was followed with a pilot study with cadres (N = 40) to assess the effectiveness and acceptability of the new tool. RESULTS: Consensus was reached on the education tool media: an audio-recording (containing full information) with a pocketbook (containing key information) as a supplement. A pilot study on the new tool reported its effectiveness in improving knowledge (p < 0.001) and demonstrated a high acceptability (all respondents stated 'Strongly Agree' or 'Agree' on all statements). CONCLUSION: This study has created a model for an education tool which can potentially be implemented for cadres to educate their communities about antibiotics in the Indonesian context.

Digoxin-quinidine and digoxin-amiodarone interactions: frequency of occurrence and monitoring in Australian repatriation hospitals.

An extensive scrutiny of 19,460 patients' charts was carried out by clinical pharmacists in six Australian Repatriation Hospitals. The incidence of the prescribing of digoxin-quinidine and digoxin-amiodarone combinations was 0.18% and 0.22% of patients, respectively, giving an overall level of 0.4% (4/1000). For both combinations, digoxin was prescribed long term in 81% of the cases and quinidine or amiodarone recently added to digoxin therapy in 44% of patients identified. Therapeutic drug monitoring of digoxin therapy was initiated by clinical pharmacists in 41% of patients and resulted in modifications to digoxin therapy in 63% of this sub-group of patients. Quinidine and amiodarone therapies were also changed in nine patients. Of particular note was the number (15 or 58%) of dosage changes or therapy cessations made to digoxin therapy for patients also receiving amiodarone which occurred as a result of clinical pharmacist intervention.

o-(beta-Hydroxyethyl)-rutoside-mediated protection of renal injury associated with cis-diamminedichloroplatinum(II)/hyperthermia treatment.

A bioflavonoid, o-(beta-hydroxyethyl)-rutoside, has been investigated for its potential to increase the therapeutic index of the combined treatment modalities of whole body hypothermia (WBH) (41.5 degrees C) and chemotherapy (cisplatin) in studies utilizing a transplantable fibrosarcoma solid tumor model in Fischer rats. When whole body WBH was induced 45 min after cisplatin administration, a significantly increased tumor growth delay was noted beyond that achieved by either treatment modality alone. The combination of WBH and cisplatin treatments, however, produced an unacceptable increase in renal injury. o-(beta-Hydroxyethyl)-rutoside administration was found to effectively block the renal injury without interfering with the antitumor efficacy of the combined regimen. Potential explanations for the ability of o-(beta-hydroxyethyl)-rutoside to affect the increase in WBH-cisplatin therapeutic regimen are discussed.

Protective effects of O-(beta-hydroxyethyl)-rutoside on cis-platinum-induced acute renal failure in the rat.

Cis-platinum (CP) is an important antineoplastic chemotherapeutic agent which causes significant renal toxicity in humans and experimental animals. This present study was designed to determine whether the free radical scavenger, O-(beta-hydroxyethyl)-rutoside (HR), exerts beneficial effects on the kidneys of rats receiving an intravenous injection of 6 mg/kg body weight of CP. Renal functional and structural changes were evaluated and quantitated in three groups of Fischer 344 female rats. Group HR/S control rats received HR treatment and a sham injection of sterile saline (S). Group S/CP rats were treated with S and intravenous CP while rats in group HR/CP received both HR and CP. The experimental group S/CP and HR/CP rats had markedly elevated blood urea nitrogen and creatinine concentrations, increased fractional excretion of sodium chloride, and decreased glomerular filtration rate when compared to group HR/S controls. Group HR/CP rats, however, had significantly lower blood urea nitrogen and creatinine values when compared to the group S/CP rats, 69 +/- 14 mg/dl versus 267 +/- 41, and 1.5 +/- 0.4 versus 5.9 +/- 0.9, respectively (p less than 0.001 for both). Renal function was also better preserved in group HR/CP rats when compared to those in group S/CP. The glomerular filtration rate in group HR/CP rats, 329 +/- 67 microliter/min/gm of kidney weight and urinary osmolality, 586 +/- 42 mOsmoles/kg H2O, was significantly greater than in group S/CP rats, 46 +/- 19 microliter/min/gm of kidney weight, and 374 +/- 28 mOsmoles/kg H2O, respectively (p less than 0.005 for both). The fractional sodium excretion was also less in group HR/CP rats, 2.7% +/- 0.6, when compared to group S/CP rats, 10.2% +/- 0.8 (p less than 0.001). There were no apparent pathological changes in group HR/S rats. In contrast, renal tubular injury and necrosis were observed in both group S/CP and HR/CP rats which were both treated with CP. The injury was confined to the S3 segment of the proximal tubule located in the outer stripe region of the outer medulla. While the injury was readily apparent in both experimental groups, group HR/CP rats had significantly less proximal tubule injury than group S/CP rats when the Wilcoxon nonparametric rank sum test was applied to the morphological data. We conclude that the free radical scavenger, O-(beta-hydroxyethyl)-rutoside, provides partial protection against the structural and functional alterations which are induced in the kidney after the intravenous administration of cis-platinum.

A comparison in rodents of renal and intestinal toxicity of cisplatin and a new water-soluble antitumor platinum complex: N-methyl-iminodiacetato-diaminocyclohexane platinum (II).

A new third-generation water-soluble platinum complex, N-methyliminodiacetato-1,2-diaminocyclohexane platinum (II) (MIDP) has been reported to have remarkable antitumor activity against several murine tumor model systems. In the present study, the renal and intestinal toxicity of MIDP was compared directly with that of cis-diamminedichloroplatinum (cisplatin). Measurement of renal physiologic parameters in Fischer 344 rats 3 and 5 days after receiving equitherapeutic doses of either cisplatin or MIDP (6.0 and 25 mg/kg, respectively) revealed that, whereas cisplatin significantly reduced glomerular filtration rates (GFR) and increased blood urea nitrogen (BUN) and serum creatinine values, MIDP produced no alteration in either GFR or BUN levels and only a slight rise (Day 5) in serum creatinine value. Histopathologic analyses by light and electron microscopy showed severe renal proximal tubular necrosis in cisplatin-treated rats yet no detectable lesions were produced by MIDP. Determination of elemental platinum content revealed that less platinum was retained in the kidneys of MIDP-treated rats than in cisplatin-treated animals. The degree of drug-mediated intestinal injury was determined for each drug by measurement of jejunal crypt cell regeneration in mice. Cisplatin reduced crypt survival by 1 log whereas no killing of crypt cells was seen even at MIDP doses exceeding the median lethal dose. Our data demonstrate that far less renal and intestinal toxicity results from administration of MIDP than from administration of cisplatin.