[Adequate medication doses for pregnant women and their unborn children]. / Gepaste medicatiedoseringen voor zwangere en foetus.

Most women use medication during pregnancy. The disposition of drugs may be altered due to changes in pregnant women's bodies. This may call for pregnancy-adjusted doses for certain medications. However, in the face of scarce evidence, such doses are generally lacking, potentially contributing to an increased risk of treatment failure or toxicity in pregnant women and their unborn children. By integrating physiological and/or population data, pharmacokinetic models can be used to determine appropriate medication dosages among pregnant women and their unborn children, as well as other patient groups for which evidence-based doses may be lacking such as children, elderly or obese patients. In order to translate model predictions into clinically usable doses, a number of conditions must be met, including careful model validation, an assessment of evidence from pharmacokinetic modelling alongside available clinical studies by multidisciplinary experts, as well as transparent communication towards end-users on the considerations for determining appropriate medication doses.

Mind the gap: Mapping variation between national and local clinical practice guidelines for acute paediatric asthma from the United Kingdom and the Netherlands.

BACKGROUND: Clinical practice guidelines (CPGs) aim to standardize clinical care. Increasingly, hospitals rely on locally produced guidelines alongside national guidance. This study examines variation between national and local CPGs, using the example of acute paediatric asthma guidance from the United Kingdom and the Netherlands. METHODS: Fifteen British and Dutch local CPGs were collected with the matching national guidance for the management of acute asthma in children under 18 years old. The drug sequences, routes and methods of administration recommended for patients with severe asthma and the tone of recommendation across both types of CPGs were schematically represented. Deviations from national guidance were measured. Variation in recommended doses of intravenous salbutamol was examined. CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II. RESULTS: British and Dutch national CPGs differed in the recommended drug choices, sequences, routes and methods of administration for severe asthma. Dutch national guidance was more rigidly defined. Local British CPGs diverged from national guidance for 23% of their recommended interventions compared to 8% for Dutch local CPGs. Five British local guidelines and two Dutch local guidelines differed from national guidance for multiple treatment steps. Variation in second-line recommendations was greater than for first-line recommendations across local CPGs from both countries. Recommended starting doses for salbutamol infusions varied by more than tenfold. The quality of the sampled local CPGs was low across all AGREE II domains. CONCLUSIONS: Local CPGs for the management of severe acute paediatric asthma featured substantial variation and frequently diverged from national guidance. Although limited to one condition, this study suggests that unmeasured variation across local CPGs may contribute to variation of care more broadly, with possible effects on healthcare quality.

CE Accreditation and Barriers to CE Marking of Pediatric Drug Calculators for Mobile Devices: Scoping Review and Qualitative Analysis.

BACKGROUND: Pediatric drug calculators (PDCs) intended for clinical use qualify as medical devices under the Medical Device Directive and the Medical Device Regulation. The extent to which they comply with European standards on quality and safety is unknown. OBJECTIVE: This study determines the number of PDCs available as mobile apps for use in the Netherlands that bear a CE mark, and explore the factors influencing the CE marking of such devices among app developers. METHODS: A scoping review of Google Play Store and Apple App Store was conducted to identify PDCs available for download in the Netherlands. CE accreditation of the sampled apps was determined by consulting the app landing pages on app stores, by screening the United Kingdom Medicines and Healthcare products Regulatory Agency's online registry of medical devices, and by surveying app developers. The barriers to CE accreditation were also explored through a survey of app developers. RESULTS: Of 632 screened apps, 74 were eligible, including 60 pediatric drug dosage calculators and 14 infusion rate calculators. One app was CE marked. Of the 20 (34%) respondents to the survey, 8 considered their apps not to be medical devices based on their intent of use or functionality. Three developers had not aimed to make their app available for use in Europe. Other barriers that may explain the limited CE accreditation of sampled PDC apps included poor awareness of European regulations among developers and a lack of restrictions when placing PDCs in app stores. CONCLUSIONS: The compliance of PDCs with European standards on medical devices is poor. This puts clinicians and their patients at risk of medical errors resulting from the largely unrestricted use of these apps.

Social Non-profit Bioentrepreneurship: Current Status and Future Impact on Global Health.

For-profit biotechnological and pharmaceutical companies have played an essential role in the research and development (R&D) of innovative medical products and drugs for many decades and embody a trillion-dollar industry. The past decades have been marked by an increase in growth of social non-profit biotechnology companies and organizations led by entrepreneurs committed to solve (global) health issues. In this review, we define the concept of social bioentrepreneurship and consider the potential impact of such ventures on global health. We analyse the current status of non-profit biotechnology and clarify the strategy, motivation, funding, and marketing techniques of these enterprises. We find that these non-profit ventures mainly focus on neglected and rare diseases by using different but also similar funding, marketing, and business strategy approaches to for-profit biotechnology enterprises. We also identify good leadership, multidisciplinary teams, and public awareness as key components to achieve long-term survival and higher success rates. Challenges faced by bioentrepreneurs include the lack of a clearly defined regulatory environment or governmental incentives to support their endeavors. Overall, with this qualitative data review and market analysis we draw a promising picture of social non-profit bioentrepreneurship and underscore its current and future impact on global health issues.

Variation in hypertension clinical practice guidelines: a global comparison.

BACKGROUND: Hypertension is the largest single contributor to the global burden of disease, affecting an estimated 1.39 billion people worldwide. Clinical practice guidelines (CPGs) can aid in the effective management of this common condition, however, inconsistencies exist between CPGs, and the extent of this is unknown. Understanding the differences in CPG recommendations across income settings may provide an important means of understanding some of the global variations in clinical outcomes related to hypertension. AIMS: This study aims to analyse the variation between hypertension CPGs globally. It aims to assess the variation in three areas: diagnostic threshold and staging, treatment and target blood pressure (BP) recommendations in hypertension. METHODS: A search was conducted on the MEDLINE repository to identify national and international hypertension CPGs from 2010 to May 2020. An additional country-specific grey-literature search was conducted for all countries and territories of the world as identified by the World Bank. Data describing the diagnosis, staging, treatment and target blood pressure were extracted from CPGs, and variations between CPGs for these domains were analysed. RESULTS: Forty-eight CPGs from across all World Bank income settings were selected for analysis. Ninety-six per cent of guidelines defined hypertension as a clinic-based BP of ≥140/90 mmHg, and 87% of guidelines recommended a target BP of < 140/90 mmHg. In the pharmacological treatment of hypertension, eight different first-step, 17 different second-step and six different third-step drug recommendations were observed. Low-income countries preferentially recommended diuretics (63%) in the first-step treatment, whilst high-income countries offered more choice between antihypertensive classes. Forty-four per cent of guidelines, of which 71% were from higher-income contexts recommended initiating treatment with dual-drug therapy at BP 160/100 mmHg or higher. CONCLUSION: This study found that CPGs remained largely consistent in the definition, staging and target BP recommendations for hypertension. Extensive variation was observed in treatment recommendations, particularly for second-line therapy. Variation existed between income settings; low-income countries prescribed cheaper drugs, offered less clinician choice in medications and initiated dual therapy at later stages than higher-income countries. Future research exploring the underlying drivers of this variation may improve outcomes for hypertensive patients across clinical contexts.