Analyzing generic and branded substitution patterns in the Netherlands using prescription data

BACKGROUND: As in other societies, pharmaceutical expenditures in the Netherlands are rising every year. As a consequence, needs for cost control are often expressed. One possible solution for cost control could come through increasing generic substitution by pharmacists. We aim to analyse the extent and nature of substitution in recent years and estimate the likelihood of generic or branded substitution in Dutch pharmacies in relation to various characteristics. METHODS: We utilized a linked prescription dataset originating from a general practitioner (GP) and a pharmacy database, both from the northern Netherlands. We selected specific drugs of interest, containing about 55,000 prescriptions from 15 different classes. We used a crossed generalized linear mixed model to estimate the effects that certain patient and pharmacy characteristics as well as timing have on the likelihood that a prescription will eventually be substituted by the pharmacist. RESULTS: Generic substitution occurred at 25% of the branded prescriptions. Generic substitution was more likely to occur earlier in time after patent expiry and to patients that were older and more experienced in their drug use. Individually owned pharmacies had a lower probability of generic substitution compared to chain pharmacies. Oppositely, branded substitution occurred in 10% of generic prescriptions and was positively related to the patients' experience in branded use. Individually owned pharmacies were more likely to substitute a generic drug to a branded compared to other pharmacies. Antidepressant and PPI prescriptions were less prone to generic and more prone to branded substitution. CONCLUSION: Analysis of prescription substitution by the pharmacist revealed strong relations between substitution and patient experience on drug use, pharmacy status and timing. These findings can be utilised to design further strategies to enhance generic substitution

The diagnostic value of clinical neurophysiology in hyperkinetic movement disorders:A systematic review

Introduction: To guide the neurologist and neurophysiologist with interpretation and implementation of clinical neurophysiological examinations, we aim to provide a systematic review on evidence of electrophysiological features used to differentiate between hyperkinetic movement disorders. Methods: A PRISMA systematic search and QUADAS quality evaluation has been performed in PubMed to identify diagnostic test accuracy studies comparing electromyography and accelerometer features. We included papers focusing on tremor, dystonia, myoclonus, chorea, tics and ataxia and their functional variant. The features were grouped as 1) basic features (e.g., amplitude, frequency), 2) the influence of tasks on basic features (e.g., entrainment, distraction), 3) advanced analyses of multiple signals, 4) and diagnostic tools combining features. Results: Thirty-eight cross-sectional articles were included discussing tremor (n = 28), myoclonus (n = 5), dystonia (n = 5) and tics (n = 1). Fifteen were rated as ‘high quality’. In tremor, the basic and task-related features showed great overlap between clinical tremor syndromes, apart from rubral and enhanced physiological tremor. Advanced signal analyses were best suited for essential, parkinsonian and functional tremor, and cortical, non-cortical and functional jerks. Combinations of electrodiagnostic features could identify essential, enhanced physiological and functional tremor. Conclusion: Studies into the diagnostic accuracy of electrophysiological examinations to differentiate between hyperkinetic movement disorders have predominantly been focused on clinical tremor syndromes. No single feature can differentiate between them all; however, a combination of analyses might improve diagnostic accuracy

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

Objectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). Method: MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. Results: We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Conclusions: Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. Key Points: • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI

Weekly high-dose cisplatin is a feasible treatment option: Analysis on prognostic factors for toxicity in 400 patients

In the present study we describe the toxicity of weekly high-dose (70-85 mg m-2) cisplatin in 400 patients (203 men, 197 women; median age 54 years) with advanced solid tumours treated in the period 1990-2001 who took part in phase I/II trials, investigating the feasibility and efficacy of weekly cisplatin alone, or in combination with paclitaxel or etoposide. Cisplatin was administered in 250 ml NaCl 3% over 3 h, for six intended administrations. The mean number of administrations was 53 (range, 1-6 administrations). Reasons not to complete six cycles were disease progression (7.5%), haematological toxicity (9%), nephrotoxicity (7%), ototoxicity (2.5%), neurotoxicity (1%), gastrointestinal toxicity (1%), cardiovascular complications (0.5%) or a combination of reasons including noncompliance and patient's request (5.5%). Logistic regression analysis was used to evaluate baseline parameters for prognostic value regarding toxicity. Leukopenia correlated with etoposide cotreatment, and thrombocytopenia with cisplatin dose and prior (platinum-based) chemotherapy. Risk factors for nephrotoxicity were older age, female gender, smoking, hypoalbuminaemia and paclitaxel coadministration. Neurotoxicity >grade I (11% of patients) was associated with prior chemotherapy and paclitaxel coadministration. Symptomatic hearing loss occurred in 15% with anaemia as the predisposing factor. We conclude that weekly high-dose cisplatin administered in hypertonic saline is a feasible treatment regimen

Septum resection in women with a septate uterus : a cohort study

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.Peer reviewedPublisher PD

Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children From Wild-type to Population Immunity:A Prospective Multicenter Cohort Study With Real-time Reporting

BACKGROUND: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data. METHODS: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity. RESULTS: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies. CONCLUSIONS: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections.</p

Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children From Wild-type to Population Immunity:A Prospective Multicenter Cohort Study With Real-time Reporting

BACKGROUND: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data. METHODS: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity. RESULTS: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies. CONCLUSIONS: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections.</p

The FOAM study : Is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial

This is an investigator initiated trial, VU medical center Amsterdam is the sponsor, contact information: prof. CJM de Groot, Department of Obstetrics and Gynaecology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands, Tel: + 31-204444444. This study is funded by ZonMw, a Dutch organization for Health Research and Development, project number 837001504. ZonMW gives financial support for the whole project. IQ Medical Ventures provides the ExEm FOAM® kits. The funding bodies have no role in the design of the study; collection, analysis, and interpretation of data; and in writing the manuscript.Peer reviewedPublisher PD

The randomised uterine septum transsection trial (TRUST) : Design and protocol

Peer reviewedPublisher PD