Switching to different generic medicines: A checklist for safety issues

Конкуренцията между предлаганите на пазара генерични лекарствени продукти води до по-ниски цени и намалени разходи за здравеопазване. Въвеждането на нов генеричен продукт обаче би могло да доведе до проблеми с прилагането му в клиничната практика. Ние изготвихме контролна карта със списък въпроси, с помощта на която да се изследват различията между продуктите. Нашата цел с този списък е да установим свойства на алтернативните генерични лекарства, които биха могли да са проблематични при клинична употреба. Навременното предсказване на евентуални проблеми подпомага внимателния подбор и обуславя въвеждането на подходящото генерично лекарство в клиничната практика. В настоящата статия разглеждаме различните позиции в нашата карта и споменаваме за някои от проблемите, които сме срещали през последните няколко години. Вярваме, че с използването на контролната карта болничните фармацевти ще могат по-добре да правят оптималния избор на генерично лекарство, съответстващо на конкретните изисквания на дадена болница.

The influence of maternal vulnerability and parenting stress on chronic pain in adolescents in a general population sample:The TRAILS study

Investigating possible psychosocial predictors of unexplained chronic pain in adolescents is crucial in understanding its development and prevention. A general population sample of adolescents (n = 2230) from the TRAILS cohort study was investigated longitudinally to assess the influence of maternal vulnerability, in terms of anxiety, depression and stress, and parenting stress at age 10-12 years, on the presence of chronic pain at age 12-15 years. Of these adolescents, 269 (12.9%) reported experiencing chronic pain, of which 77% reported severe chronic pain and 22% reported multiple chronic pain. Maternal anxiety, maternal stress and higher levels of parenting stress were related to chronic pain at a later age. Subgroup analyses showed similar results for adolescents with severe chronic pain. Mediation analyses indicated that parenting stress mediates the effect between maternal anxiety, or stress, and chronic pain. The findings suggest that interventions to diminish maternal feelings of anxiety and stress, while in turn adjusting maternal behaviour, may prevent the development of chronic pain in adolescence

Failure of target attainment of beta-lactam antibiotics in critically ill patients and associated risk factors: a two-center prospective study (EXPAT)

Background: Early and appropriate antibiotic dosing is associated with improved clinical outcomes in critically ill patients, yet target attainment remains a challenge. Traditional antibiotic dosing is not suitable in critically ill patients, since these patients undergo physiological alterations that strongly affect antibiotic exposure. For betalactam antibiotics, the unbound plasma concentrations above at least one to four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval (100%ƒT>1–4×MIC) have been proposed as pharmacodynamic targets (PDTs) to maximize bacteriological and clinical responses. The objectives of this study are to describe the PDT attainment in critically ill patients and to identify risk factors for target non-attainment. Methods: This prospective observational study was performed in two ICUs in the Netherlands. We enrolled adult patients treated with the following beta-lactam antibiotics: amoxicillin (with or without clavulanic acid), cefotaxime, ceftazidime, ceftriaxone, cefuroxime, and meropenem. Based on five samples within a dosing interval at day 2 of therapy, the time unbound concentrations above the epidemiological cut-off (ƒT > MICECOFF and ƒT > 4×MICECOFF) were determined. Secondary endpoints were estimated multivariate binomial and binary logistic regression models, for examining the association of PDT attainment with patient characteristics and clinical outcomes. Results: A total of 147 patients were included, of whom 63.3% achieved PDT of 100%ƒT > MICECOFF and 36.7% achieved 100%ƒT > 4×MICECOFF. Regression analysis identified male gender, estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 , and high body mass index (BMI) as risk factors for target non-attainment. Use of continuous renal replacement therapy (CRRT) and high serum urea significantly increased the probability of target attainment. In addition, we found a significant association between the 100%ƒT > MICECOFF target attainment and ICU length of stay (LOS), but no significant correlation was found for the 30-day survival. Conclusions: Traditional beta-lactam dosing results in low target attainment in the majority of critically ill patients. Male gender, high BMI, and high eGFR were significant risk factors for target non-attainment. These predictors, together with therapeutic drug monitoring, may help ICU clinicians in optimizing beta-lactam dosing in critically ill patients

Prevalence and determinants of intravenous admixture preparation errors:A prospective observational study in a university hospital

Background Intravenous admixture preparation errors (IAPEs) may lead to patient harm. Insight into the prevalence as well as the determinants associated with these IAPEs is needed to elicit preventive measures. Aim The primary aim of this study was to assess the prevalence of IAPEs. Secondary aims were to identify the type, severity, and determinants of IAPEs. Method A prospective observational study was performed in a Dutch university hospital. IAPE data were collected by disguised observation. The primary outcome was the proportion of admixtures with one or more IAPEs. Descriptive statistics were used for the prevalence, type, and severity of IAPEs. Mixed-effects logistic regression analyses were used to estimate the determinants of IAPEs. Results A total of 533 IAPEs occurred in 367 of 614 admixtures (59.8%) prepared by nursing staff. The most prevalent errors were wrong preparation technique (n = 257) and wrong volume of infusion fluid (n = 107). Fifty-nine IAPEs (11.1%) were potentially harmful. The following variables were associated with IAPEs: multistep versus single-step preparations (adjusted odds ratio [OR(adj)] 4.08, 95% confidence interval [CI] 2.27–7.35); interruption versus no interruption (OR(adj) 2.32, CI 1.13–4.74); weekend versus weekdays (OR(adj) 2.12, CI 1.14–3.95); time window 2 p.m.-6 p.m. versus 7 a.m.-10 a.m. (OR(adj) 3.38, CI 1.60–7.15); and paediatric versus adult wards (OR(adj) 0.14, CI 0.06–0.37). Conclusion IAPEs, including harmful IAPEs, occurred frequently. The determinants associated with IAPEs point to factors associated with preparation complexity and working conditions. Strategies to reduce the occurrence of IAPEs and therefore patient harm should target the identified determinants

Quality of life and health status of Indonesian women with breast cancer symptoms before the definitive diagnosis

__Objectives__ Breast cancer (BC) is prevalent in low and middle-income countries (LMICs) where the majority of cases are diagnosed in late stages. The aims of this study were: (1) to assess quality of life (QOL) and health status of Indonesian women with BC symptoms before definitive diagnosis; (2) to compare QOL and health status between women with BC symptoms before definitive diagnosis and Indonesian women in general; (3) to evaluate the association between demographic variables (age, residence, social economic status and education level) and QOL within the Indonesian women with BC symptoms before definitive diagnosis. __Methods__ We used WHOQOL-BREF to measure QOL and EQ-5D-5L for health status. Multivariate analysis of covariance (MANCOVA) was used to compare QOL and health status between women with BC symptoms and women from the general Indonesian population in order to control for confounders. Regression analyses were used for testing the association between the demographic variables, QOL, and health status. __Results__ In comparison with the data from the women from the general population (n = 471), the women with BC symptoms (n = 132) reported lower QOL, especially in physical and psychological domains. They also reported more problems in all dimensions of health status. Higher education and monthly income were positively associated with QOL and health status among the women with BC symptoms. __Conclusion__ Before receiving a definitive diagnosis, women who visit hospitals with symptoms of BC, report a lower QOL and health status than women in general. Our results suggest that healthcare providers should provide targeted strategies for women with BC symptoms to improve their QOL

Employing quality control and feedback to the EQ-5D-5L valuation protocol to improve the quality of data collection

Objectives: In valuing health states using generic questionnaires such as EQ-5D, there are unrevealed issues with the quality of the data collection. The aims were to describe the problems encountered during valuation and to evaluate a quality control report and subsequent retraining of interviewers in improving this valuation. Methods: Data from the first 266 respondents in an EQ-5D-5L valuation study were used. Interviewers were trained and answered questions regarding problems during these initial interviews. Thematic analysis was used, and individual feedback was provided. After completion of 98 interviews, a first quantitative quality control (QC) report was generated, followed by a 1-day retraining program. Subsequently individual feedback was also given on the basis of follow-up QCs. The Wilcoxon signed-rank test was used to assess improvements based on 7 indicators of quality as identified in the first QC and the QC conducted after a further 168 interviews. Results: Interviewers encountered problems in recruiting respondents. Solutions provided were: optimization of the time of interview, the use of broader networks and the use of different scripts to explain the project’s goals to respondents. For problems in interviewing process, solutions applied were: developing the technical and personal skills of the interviewers and stimulating the respondents’ thought processes. There were also technical problems related to hardware, software and internet connections. There was an improvement in all 7 indicators of quality after the second QC. Conclusion: Training before and during a study, and individual feedback on the basis of a quantitative QC, can increase the validity of values obtained from generic questionnaires

Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients

Purpose: To develop and validate a population pharmacokinetic model of ciprofloxacin intravenously in critically ill patients, and determine target attainment to provide guidance for more effective regimens. Methods: Non-linear mixed-effects modelling was used for the model development and covariate analysis. Target attainment of an ƒAUC0–24/MIC ≥ 100 for different MICs was calculated for standard dosing regimens. Monte Carlo simulations were performed to define the probability of target attainment (PTA) of several dosing regimens. Results: A total of 204 blood samples were collected from 42 ICU patients treated with ciprofloxacin 400–1200 mg/day, with median values for age of 66 years, APACHE II score of 22, BMI of 26 kg/m2, and eGFR of 58.5 mL/min/1.73 m2. The median ƒAUC0–24 and ƒCmax were 29.9 mg•h/L and 3.1 mg/L, respectively. Ciprofloxacin pharmacokinetics were best described by a two-compartment model. We did not find any significant covariate to add to the structural model. The proportion of patients achieving the target ƒAUC0–24/MIC ≥ 100 were 61.9% and 16.7% with MICs of 0.25 and 0.5 mg/L, respectively. Results of the PTA simulations suggest that a dose of ≥ 1200 mg/day is needed to achieve sufficient ƒAUC0–24/MIC ratios. Conclusions: The model described the pharmacokinetics of ciprofloxacin in ICU patients adequately. No significant covariates were found and high inter-individual variability of ciprofloxacin pharmacokinetics in ICU patients was observed. The poor target attainment supports the use of higher doses such as 1200 mg/day in critically ill patients, while the variability of inter-individual pharmacokinetics parameters emphasizes the need for therapeutic drug monitoring to ensure optimal exposure

A protocol for a cluster-randomized controlled trial of a self-help psycho-education programme to reduce diagnosis delay in women with breast cancer symptoms in Indonesia

Background: Breast cancer (BC) is the most frequent cancer occurring in women across the world. Its mortality rate in low-middle income countries (LMICs) is higher than in high-income countries (HICs), and in Indonesia BC is the leading cause of cancer deaths among women. Delay in breast cancer diagnosis negatively impacts cancer prognosis. Only about 30% of patients who come to the hospital to check on their breast abnormalities, continue thorough examination to biopsy to get a diagnosis based on the results of anatomical pathology. Many Indonesian women with breast cancer were already in an advanced stage when starting treatment. Therefore, delay in diagnosis is a serious problem that needs to be addressed. The present study will investigate whether our newly developed self-help psycho-educational programme, "PERANTARA", for women with breast cancer symptoms is effective to reduce patient diagnosis delay in Indonesia. Methods: A cluster-randomized controlled trial will be conducted in 106 patients in four hospitals in Bandung, West Java, Indonesia. Data will be collected at baseline (pre-assessment), 7 days after the intervention (post-assessment), and at 3months (follow-up assessments). The primary outcome is delay in diagnosis and treatment. Secondary outcomes are breast cancer knowledge, anxiety and depression, and quality of life. Exploratively, adherence with treatment will be measured too. Data will be analysed by hierarchical linear modelling (HLM) to assess differential change over time. Discussion: If proven effective, PERANTARA will be evaluated and implemented in a diversity of settings for local cares (such as in POSYANDU, PUSKESMAS) that provide health education/psycho-education for women with breast symptoms. Trial registration: ISRCTN1257073

Dynamics of the QTc interval over a 24-h dose interval after start of intravenous ciprofloxacin or low-dose erythromycin administration in ICU patients

QTc interval prolongation is an adverse effect associated with the use of fluoroquinolones and macrolides. Ciprofloxacin and erythromycin are both frequently prescribed QTc-prolonging drugs in critically ill patients. Critically ill patients may be more vulnerable to developing QTc prolongation, as several risk factors can be present at the same time. Therefore, it is important to know the QTc-prolonging potential of these drugs in the intensive care unit (ICU) population. The aim of this study was to assess the dynamics of the QTc interval over a 24-hour dose interval during intravenous ciprofloxacin and low-dose erythromycin treatment. Therefore, an observational study was performed in ICU patients (>= 18 years) receiving ciprofloxacin 400 mg t.i.d. or erythromycin 100 mg b.i.d. intravenously. Continuous ECG data were collected from 2 h before to 24 h after the first administration. QT-analyses were performed using high-end holter software. The effect was determined with a two-sample t-test for clustered data on all QTc values. A linear mixed model by maximum likelihood was applied, for which QTc values were assessed for the available time intervals and therapy. No evident effect over time on therapy with ciprofloxacin and erythromycin was observed on QTc time. There was no significant difference (p = 0.22) in QTc values between the ciprofloxacin group (mean 393 ms) and ciprofloxacin control group (mean 386 ms). The erythromycin group (mean 405 ms) and erythromycin control group (mean 404 ms) neither showed a significant difference (p = 0.80). In 0.6% of the registrations (1.138 out of 198.270 samples) the duration of the QTc interval was longer than 500 ms. The index groups showed slightly more recorded QTc intervals over 500 ms. To conclude, this study could not identify differences in the QTc interval between the treatments analyzed.Clinical Pharmacy and Toxicolog