International trends in clozapine use: a study in 17 countries.

OBJECTIVE: There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis. METHOD: A repeated cross-sectional design was applied to data extracts (2005-2014) from 17 countries worldwide. RESULTS: In 2014, overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons) and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100 000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014, clozapine use increased in almost all studied countries (relative increase: 7.8-197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range: 0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10-19 years), clozapine use was highest in Finland (24.7/100 000) and in the publicly insured US cohort (15.5/100 000). CONCLUSION: While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation.

Development of clinical tools to estimate the breathing effort during high-flow oxygen therapy: A multicenter cohort study.

INTRODUCTION AND OBJECTIVES: Quantifying breathing effort in non-intubated patients is important but difficult. We aimed to develop two models to estimate it in patients treated with high-flow oxygen therapy. PATIENTS AND METHODS: We analyzed the data of 260 patients from previous studies who received high-flow oxygen therapy. Their breathing effort was measured as the maximal deflection of esophageal pressure (ΔPes). We developed a multivariable linear regression model to estimate ΔPes (in cmH2O) and a multivariable logistic regression model to predict the risk of ΔPes being >10 cmH2O. Candidate predictors included age, sex, diagnosis of the coronavirus disease 2019 (COVID-19), respiratory rate, heart rate, mean arterial pressure, the results of arterial blood gas analysis, including base excess concentration (BEa) and the ratio of arterial tension to the inspiratory fraction of oxygen (PaO2:FiO2), and the product term between COVID-19 and PaO2:FiO2. RESULTS: We found that ΔPes can be estimated from the presence or absence of COVID-19, BEa, respiratory rate, PaO2:FiO2, and the product term between COVID-19 and PaO2:FiO2. The adjusted R2 was 0.39. The risk of ΔPes being >10 cmH2O can be predicted from BEa, respiratory rate, and PaO2:FiO2. The area under the receiver operating characteristic curve was 0.79 (0.73-0.85). We called these two models BREF, where BREF stands for BReathing EFfort and the three common predictors: BEa (B), respiratory rate (RE), and PaO2:FiO2 (F). CONCLUSIONS: We developed two models to estimate the breathing effort of patients on high-flow oxygen therapy. Our initial findings are promising and suggest that these models merit further evaluation.

Reducing the costs of paediatric antibiotic prescribing in the community by implementing guideline recommendations.

WHAT IS KNOWN AND OBJECTIVE: Italian children receive a high number of antibiotic prescriptions, and the use of second-choice antibiotics is common. A few studies in other countries have demonstrated that the implementation of international guidelines for the most common paediatric diseases may reduce the associated costs. A cost analysis of the expenditure for antibiotic prescriptions in outpatient children in the Lombardy region (Italy) and for each of the region's local health units (LHUs) was performed using a pharmacoepidemiological approach. The safety and cost impact associated with a quali-quantitative improvement in antibiotic prescribing was estimated. METHODS: The data source was the Lombardy region's prescription database (year 2008) for outpatient children <14 years old. The average total expenditure for each package, and per capita, was calculated for each active substance considered and for each LHU. An estimate of the possible cost reduction was elaborated using, as a reference, the prescription profile of a group of paediatricians that has been involved in initiatives concerning care for years. The hospital admission rates for acute respiratory infections (ARI) and their major complications were evaluated at the regional level and in the group of children followed by the reference paediatricians. RESULTS AND DISCUSSION: The cost reduction estimate reveals a possible decrease in antibiotic expenditure of about 3·6 million euros (-19·5%) in the Lombardy region. Large variability was observed between different LHUs (-33·3 to +9·2% of difference). The hospital admission rate was not different when comparing the group of children followed by the reference paediatricians to the rest of the study population, but the hospital admission rate for ARI was lower in the reference group (χ(2) = 16·4, P < 0·001). WHAT IS NEW AND CONCLUSION: This is the first Italian study to evaluate the costs related to a specific prescription profile, which already exists in the real setting, hypothesizing its application in a large outpatient child population of the same geographical area. The results show that by improving prescribing appropriateness, it is possible to reduce the expenditure associated with antibiotic prescriptions to outpatient children in the Lombardy region by about one-fifth. The lower rate of hospital admissions for ARI suggests that the adopted profile is also beneficial to children's health.

Bactericidal activity of erythromycin in the respiratory system.

In vivo and in vitro studies were carried out to assess tha levels in bronchial mucus of ampicillin, amoxycillin, bacampicillin, cefotaxime and erythromycin, and to compare their minimum bactericidal concentrations and killing rate against hospital strains of Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae. Both the percentage ratios of serum/mucus concentration peaks and of serum/mucus area under the concentration time curve values were higher for erythromycin than for the other antibiotics. Determination of the minimum bactericidal concentrations showed that the bacterial strains were sensitive to small quantities of erythromycin, and the time necessary to sterilize inocula varied from 4 to 16 hours.

The quantitative determination of neomycin sulphate by a diffusion technique on agar plates by the method of the European Pharmacopoeia, 2nd edition--evaluation of precision and reproducibility of the method.

The medium recommended by the European Pharmacopoeia (EP), 2nd edition, for the microbiological determination of neomycin by the agar diffusion method was tested and compared with the medium recommended by the EP, 1st edition. The tests were carried out in different laboratories. The medium recommended by the EP, 2nd edition, gave greater precision and reproducibility than the previous medium. The possibility of using a reference standard of almost pure neomycin B for both the determination of framycetin and neomycin was evaluated. The results demonstrated that the medium recommended by the EP, 2nd edition, gave better precision and reproducibility. Difficulty in achieving valid assays was practically the same with both media.