Nature and frequency of prescription modifications in community pharmacies: A nationwide study in the Netherlands.

AIMS: To investigate the nature and frequency of prescription modifications in Dutch community pharmacies. METHODS: In this cross-sectional study, Dutch community pharmacists documented prescription modifications in their pharmacy during 1 predetermined day. Pharmacists from all Dutch community pharmacies were invited to participate. A prescription modification was defined as any modification in a prescription for a medicine or other healthcare product because of an administrative problem, logistic issue or potential drug-related problem (DRP). All documented modifications were assessed to establish the nature and frequency of prescription modifications. RESULTS: Pharmacists in 275 pharmacies completed the study. A modification was performed in 5.5% of all prescriptions. 1.3% of the prescriptions contained an administrative problem, of which insufficient specification of the dosing regimen was most common (63.1%). A modification was performed due to a logistic issue in 2.4% of the prescriptions. The most frequently recorded issues were unavailability of medication (40.9%) and obligatory product substitutions due to reimbursement policies (33.2%). A modification was performed in 1.8% of the prescriptions to solve or prevent potential DRPs. Of these, 69.2% was potentially clinically relevant according to the pharmacist concerned. The most frequently prevented potential DRP was an incorrect strength or dose (31.9%). CONCLUSION: Dutch community pharmacists modified almost 1 in 20 prescriptions per pharmacy. The nature of the modifications reflects current community pharmacy practice, in which pharmacists frequently deal with logistic issues and intervene to solve or prevent for DRPs several times a day. The majority of the DRPs were considered to be potentially clinically relevant.

Use of resuscitation promoting factors to screen for tuberculosis infection in household-exposed children in The Gambia.

BACKGROUND: Interferon-γ release assays (IGRA) with Resuscitation promoting factor (Rpf) proteins enhanced tuberculosis (TB) screening and diagnosis in adults but have not been evaluated in children. Children often develop paucibacillary TB and their immune response differs from that of adults, which together affect TB disease diagnostics and immunodiagnostics. We assessed the ability of Rpf to identify infection among household TB-exposed children in The Gambia and investigated their ability to discriminate Mycobacterium tuberculosis complex (MTBC) infection from active TB disease in children. METHODS: Detailed clinical investigations were done on 93 household TB-exposed Gambian children and a tuberculin skin test (TST) was administered to asymptomatic children. Venous blood was collected for overnight stimulation with ESAT-6/CFP-10-fusion protein (EC), purified protein derivative and RpfA, B, C, D and E. Interferon gamma (IFN-γ) production was measured by ELISA in supernatants and corrected for the background level. Infection status was defined by IGRA with EC and TB disease by mycobacterial confirmation and/or clinical diagnosis. We compared IFN-γ levels between infected and uninfected children and between infected and TB diseased children using a binomial logistic regression model while correcting for age and sex. A Receiver Operating Characteristics analysis was done to find the best cut-off for IFN-γ level and calculate sensitivity and specificity. RESULTS: Interferon gamma production was significantly higher in infected (IGRA+, n = 45) than in uninfected (IGRA-, n = 20) children after stimulation with RpfA, B, C, and D (P = 0.03; 0.007; 0.03 and 0.003, respectively). Using RpfB and D-specific IFN-γ cut-offs (33.9 pg/mL and 67.0 pg/mL), infection was classified with a sensitivity-specificity combination of 73-92% and 77-72% respectively, which was similar to and better than 65-75% for TST. Moreover, IFN-γ production was higher in infected than in TB diseased children (n = 28, 5 bacteriologically confirmed, 23 clinically diagnosed), following RpfB and D stimulation (P = 0.02 and 0.03, respectively). CONCLUSION: RpfB and RpfD show promising results for childhood MTBC infection screening, and both performed similar to and better than the TST in our study population. Additionally, both antigens appear to discriminate between infection and disease in children and thus warrant further investigation as screening and diagnostic antigens for childhood TB.

A dispersion based model for anaerobic digestion of solid cattle wastes in a stratified thermophilic accumulation system.

A dynamic model has been developed to describe the anaerobic digestion of solid cattle waste in an accumulation system (AC). To calibrate the model an experiment was carried out at a lab-scale AC at 50 degrees C. The predicted methane production shows a very good agreement (i.e. R2 = 0.998) with the experimental data. However less agreement is evident for the intermediates. After model validation the model was applied to study the effect of different aspect ratios on the system performance. An optimum aspect ratio of 2-3 could be determined.

Anaerobic digestion of solid animal waste in an accumulation system at mesophilic and thermophilic conditions, start up.

The anaerobic digestion of solid animal wastes has been studied in an accumulation system (AC) at a filling time of 60 days followed by about 50 days batch digestion at 40 and 50degrees C. Poor mixing conditions during anaerobic digestion of solid wastes promote stratification of the substrate and intermediate products along the reactor height. The effect of layers stratification has also been followed in the AC system. The results showed a pronounced stratification of both COD(dis) and VFA concentrations along the AC system height. The temperature had a minor effect on the methane yield. The results also showed that methanogenesis was rate limiting in the AC system while the hydrolysis was the rate-limiting step during batch digestion.

Quantitative determination of total molar concentrations of bioaccumulatable organic micropollutants in water using C18 empore disk and molar detection techniques.

A highly sensitive and quantitative group parameter to determine total molar concentrations of organic micropollutants that can bioaccumulate in the lipid phase of aquatic organisms from effluents, surface water, and drinking water has been developed. C18 empore disk was used as a surrogate lipid phase. The partition process between water and C18 empore disk was employed to simulate the bioaccumulation process. After partition extraction of the water sample, the empore disk was extracted with cyclohexane, and total molar concentrations were determined in these extracts using vapor pressure osmometry (VPO) and gas chromatography/mass spectrometry (GC/MS), respectively. Total molar concentrations bioaccumulated in aquatic biota were estimated from the cyclohexane concentrations. Good accuracy for the total molar determination was obtained using VPO, due to the practically constant molar response factors (43.1 +/- 1.7 V/M) for a wide compound range and to excellent additivity of individual compound responses. Satisfying reproducibility (0-8.3%) of VPO was obtained for sample extracts. The detection limit of VPO in cyclohexane extracts corresponded to 0.60 mM in the lipid phase of aquatic biota. A minimal separation GC/MS system was developed, which enabled highly sensitive and sufficiently accurate total molar determinations. The reproducibility of the GC/MS determination for samples ranged from 0.7 to 22%. The detection limit of GC/MS in cyclohexane extracts corresponded to 0.044 mM in the lipid phase. The determined total molar concentrations in the lipid phase of aquatic biota were in the range of 0.139-168 mM for effluents, 0.26-1.34 mM for surface water systems, and < 0.044 mM for drinking water.

Hydrophobicity of complex organic mixtures.

Hydrophobicity is an important property in risk assessment of chemicals. A group parameter that reflects the hydrophobicity of technical mixtures is not yet available. However, many substances are complex organic mixtures, for which it is practically impossible to determine each component separately. An experimental procedure to measure the hydrophobicity of organic mixtures without knowledge of the individual components was developed and tested for a mixture of benzene and twelve chlorobenzenes. This procedure is based on separation of the mixture into fractions of increasing hydrophobicity by reversed-phase HPLC, after which the total molar concentration in each fraction is determined by vapour pressure osmometry. The obtained information on hydrophobicity can be used for assessing bioaccumulation and sediment sorption after emission of the mixture to water has occurred.

Biotransformation and quantitative determination of sulfur-containing metabolites of 1,4-dibromobutane in the rat.

Two stable sulfur-containing metabolites were isolated from rat urine following administration of the mutagenic 1,4-dibromobutane. They were identified as tetrahydrothiophene and 3-hydroxysulfolane by gas chromatography and gas chromatography-mass spectrometry and were found to be excreted in 48-hr urine, representing 5.8 +/- 1.1 and 57 +/- 15% of the dose of 1,4-dibromobutane, respectively. When urines of rats treated with 1,4-dibromobutane were collected in a buffer of pH 1.0, however, only 3-hydroxysulfolane was found. It was indirectly shown that an N-acetyl-S-(beta-alanyl)tetrahydrothiophenium salt was present in urine and that this metabolite is probably the precursor of tetrahydrothiophene. The latter product is only formed at higher pH values and quantified after addition of NaOH to buffered urines. Tetrahydrothiophene is probably also formed under physiological conditions in vivo from the N-acetyl-S-(beta-alanyl)-tetrahydrothiophenium salt, but in this case it is subsequently transformed to 3-hydroxysulfolane. Based on these findings, a biotransformation scheme of 1,4-dibromobutane in the rat is proposed. The extensive metabolism via glutathione conjugation resulted in efficient detoxification of 1,4-dibromobutane.