Danish Medicines Agency

This study explores the relationship between various types of innovation and productivity growth in small and medium-sized enterprises (SMEs) within Vietnam, a factor-driven economy. Utilising a longitudinal dataset from three surveys of 3,550 Vietnamese manufacturing SMEs, the study employs regression analysis to account for dual causality between innovation and factor productivity growth. The results reveal that process innovation leads to greater productivity gains compared to product modification and product innovation strategies. The findings underscore the importance of process innovation in enhancing productivity in factor-driven economies, where firms primarily exploit unskilled labour and natural resources. The study also highlights the need for policymakers to tailor innovation support strategies to the unique contexts of factor-driven economies, emphasising process innovations that leverage existing factor endowments. The research contributes to the limited literature on innovation in the lowest stages of economic development and provides practical insights for promoting sustainable economic growth in developing countries.

BackgroundThe Pharmacovigilance Risk Assessment Committee (PRAC) plays a central role in the European Union’s pharmacovigilance system, evaluating drug safety through several procedures and activities. Despite its central role, few studies have quantitatively investigated the PRAC’s activities from a system’s perspective.ObjectiveThis study aims to map PRAC’s evaluation of safety signals and concerns using antidiabetic products as a case. It characterises the drugs and adverse events involved, analyses the PRAC-led regulatory procedures where the safety signals and concerns were evaluated, and provides a comprehensive review of PRAC meeting minutes.MethodsFrom PRAC meeting minutes, we retrieved information on all antidiabetic drug-related adverse events discussed from 2012 to 2022. We identified drug-adverse event evaluations based on the discussion content. These were described by drug classes, System Organ Classes, PRAC procedures, and the evaluation outcomes corresponding to recommendations for regulatory actions. We also analysed the sequence of PRAC-led procedures and activities addressing drug-adverse event pairs across meeting minutes.ResultsA total of 321 drug-adverse event pairs were identified, with 14 pairs associated with drug classes. Second-generation antidiabetic agents, including sodium-glucose transport protein-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase 4 inhibitors, were the most frequently discussed. Of these, 62 pairs underwent multiple evaluations, resulting in a total of 413 evaluations. In 48% of evaluations, no regulatory action was required. Most evaluations (97%) were concluded in a single procedure, and 66% were concluded in one meeting. Periodic safety update reports accounted for 54% of drug-adverse event evaluations and updates to product information were the most frequent outcome. Signal assessment and prioritisation procedures, while less common, resulted in more diverse recommendations for regulatory action. Referrals were infrequent (N = 5) and were often triggered by the signal assessment and prioritisation procedure.ConclusionsPeriodic safety update reports are the primary source for PRAC evaluations of safety signals although they are not intended for notification of new urgent safety information. Compared with periodic safety update reports, the signal assessment and prioritisation procedure evaluates fewer signals but leads to a wider range of regulatory actions, from risk minimisation measures to referrals. This difference may be attributed to the fact that signals detected in periodic safety update reports are not intended for urgent safety issues, these should be assessed through the signal assessment and prioritisation procedure, as the latter involves real-time signal management, whereas the periodic safety update reports are conducted at predefined intervals.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-025-01536-7.

Floods stand out as the most frequent and costly natural disaster in Europe. In the EU alone, there have been documented more than 1500 flood events since 1980, causing over 4300 deaths and more than €170 billion in economic damages.Due to the compounded developments of urbanization and climate change, the frequency of floods is expected to increase with severe impacts, possibly endangering lives and leading to economic losses. Moreover, floods mobilize pollutants stored in the subsurface and urban areas. Thus, current efforts, such as coastal barriers, restoration of river courses, or resilient city and landscape planning, focus on reducing vulnerability and risks from flooding. But to implement such measures, detailed information on where and when flooding occurs is necessary. This study aims to improve and implement satellite-based mapping of flood extent under Danish conditions by presenting different methods and algorithms utilizing Sentinel-1 (S1) Synthetic Aperture Radar (SAR) imagery, digital elevation models (DEM) and river geometry. In the broader literature, various methods have been proven to successfully map flood extent, such as deep learning (DL) and change detection (CD) as employed in the Global Flood Awareness System. However, DL require extensive training and labeled data that are often not available, and CD is reliant on a comprehensive pre-processing procedure of antecedent satellite imagery or accompanied with a datacube-based algorithm that exploits the satellite orbit repetition. While these methods can provide excellent results, the steep data requirements and pre-processing procedures hinder practical usage. On the other hand, single-temporal image flood extent mapping algorithms relying on histogram analysis offering a straightforward approach potentially yielding satisfying results, especially when accompanied by techniques such as image decomposition, region-growing, active contour models or image texture algorithms. But for single-temporal image histogram analysis to work in an automated setup, the two main problems, namely class imbalance and class overlap must be addressed properly. This study proposes a novel approach for single-temporal image histogram analysis by combining automatic local histogram thresholding with two image decomposition techniques for image tiling using a quadtree and a novel combination of k-means clustering and box tiling. This study implements a bimodality test and a subsequent local-threshold selection using gaussian mixture modelling and kernel-density smoothening, followed by contextual segmentation using region-growing. Furthermore, a novel approach for improving flood extent segmentation using a combination of DEM information, geographical stream location and region-growing is presented. The proposed method is showcased for two different flood events in Denmark from 2015 to 2022 using 10 x 10 m interferometric wide swath S1 SAR imagery. Results are evaluated using Sentinel-2 optical imagery where available, and otherwise evaluated against high-precision permanent water maps. Moreover, we utilize gauged timeseries of stream water level to evaluate the temporal evolution of flood extent over the period of a flood event.  

Introduction. Increasing microbial resistance to conventional pharmaceuticals calls for nonpharmaceutical treatments of vaginitis. This systematic review summarizes the efficacy of the antiseptic agent boric acid (BA) as a treatment option for microbial vaginitis in comparison to conventional therapies and proposes clinical recommendations. Materials and Methods. PubMed and Embase were searched for “boric acid” and “microbial vaginitis.” A protocol was registered on PROSPERO (CRD42020160146). Inclusion criteria included clinical trials, observational and interventional studies, including case series/reports. Exclusion criteria included in vitro and animal studies, non‐English language, and no BA treatment outcome. Primary outcomes included microbial, clinical, and complete cure. Secondary outcomes included adverse events, relapse/reinfection rates, evidence levels, microorganisms, treatment regimens, and follow‐up time. Data were extracted to a predefined Excel sheet. Results. Of 195 identified unique articles, 54 were retrieved and 41 met our inclusion criteria. Heterogeneity precluded the conduction of a meta‐analysis. Conclusion. An average cure rate of 76% was found for vulvovaginal candidiasis BA treatment. Recurrent bacterial vaginosis was controlled with BA and 5‐nitroimidazole with promising results. Maintenance BA was equal to maintenance oral itraconazole therapy in vulvovaginal candidiasis and bacterial vaginosis in a retrospective study. Prolonged BA monotherapy cured three of six recurrent Trichomonas infections. Adverse events (7.3%) were typically mild and temporary. Based on our findings and the rising antimicrobial therapy resistance, we suggest intravaginal BA 600 mg/day for 2 weeks for (recurrent) vulvovaginal candidiasis and 600 mg/day for 2‐3 weeks for recurrent bacterial vaginosis. Rare resistant Trichomonas infections can be treated with BA 600 mg × 2/day for months and in combination with oral antimicrobials. We suggest a maintenance regimen of BA 600 mg × 2/week for recurrent vulvovaginal candidiasis. In case of resistant bacterial vaginosis, we suggest BA 600 mg × 2‐3/week. Data on maintenance therapy and BA treatment of bacterial vaginosis and trichomoniasis are however limited.

Integration of molecular characterization of lymphomas in clinical diagnostics may improve subclassification and risk-stratification, and we implemented a next generation sequencing (NGS) analysis as part of routine diagnostic work-up of all mature B-cell non-Hodgkin's lymphoma (B-NHL). Here, we present data of mutational profiles with potential complementary diagnostic, prognostic, and predictive value detected in our consecutive non-selected cohort of B-NHL patients. NGS results from 298 patients with both newly diagnosed and relapsed/refractory disease were included as a single center study. NGS was performed as routine analysis together with standard diagnostic work-up using a custom-made amplicon PCR-based multiplex NGS panel covering all coding exons and consensus splice sites in 59 genes. Mutations were detected in 94% of the 298 samples. Most lymphomas could be classified definitively, but 24 cases were classified as small B-cell lymphomas without defining characteristics. Of these, 50% (12/24 cases) could retrospectively be assigned a likely diagnostic subtype according to mutational findings. Implementation of a 59 gene exome sequencing panel added diagnostic value to 50% of unclassified cases and provided in 94% of the cases possible biomarkers for disease monitoring as well as potential diagnostic, prognostic, and predictive markers for future studies.

ObjectiveThe aim of this study was to assess the marketing status of the new paediatric medicinal products listed in the 10-year report as initially authorised between 2007 and 2016, reflecting the product availability in four Nordic countries.DesignThis is a cross-sectional study.SettingAnalysis of the national medicine agency’s databases in Denmark, Finland, Norway and Sweden.Data sourceNew medicinal products with paediatric indications and new paediatric formulations listed in the Annex of European Medicines Agency’s EU Paediatric Regulation 10-year report.Data analysisThe products were classified according to national marketing status between January 2019 and March 2019, whether a product was authorised and whether the product was marketed.Main outcome measuresThe percentages of the new medicinal products with paediatric indications and new paediatric formulations having a valid marketing authorisation and being marketed, both in terms of the sums of all countries and separately for each country.ResultsAcross the four countries, 21%–32% (16/76–24/76) of the new medicinal products were not marketed. Of the new formulations relevant to children, 29%–50% (16/56–28/56) were not marketed, and a significant proportion of these products had never been marketed.ConclusionsThis study reflects the reality of the implementation of the Paediatric Regulation. The results show that several new paediatric medicines and new formulations are not marketed. This affects the product availability. Similar data from other countries are needed to evaluate the overall European status to find remedies to current situation and increase the availability of the medicines for children.

Cockayne syndrome (CS) is a rare premature aging disease, most commonly caused by mutations of the genes encoding the CSA or CSB proteins. CS patients display cachectic dwarfism and severe neurological manifestations and have an average life expectancy of 12 years. The CS proteins are involved in transcription and DNA repair, with the latter including transcription‐coupled nucleotide excision repair (TC‐NER). However, there is also evidence for mitochondrial dysfunction in CS, which likely contributes to the severe premature aging phenotype of this disease. While damaged mitochondria and impaired mitophagy were characterized in mice with CSB deficiency, such changes in the CS nematode model and CS patients are not fully known. Our cross‐species transcriptomic analysis in CS postmortem brain tissue, CS mouse, and nematode models shows that mitochondrial dysfunction is indeed a common feature in CS. Restoration of mitochondrial dysfunction through NAD+ supplementation significantly improved lifespan and healthspan in the CS nematodes, highlighting mitochondrial dysfunction as a major driver of the aging features of CS. In cerebellar samples from CS patients, we found molecular signatures of dysfunctional mitochondrial dynamics and impaired mitophagy/autophagy. In primary cells depleted for CSA or CSB, this dysfunction can be corrected with supplementation of NAD+ precursors. Our study provides support for the interconnection between major causative aging theories, DNA damage accumulation, mitochondrial dysfunction, and compromised mitophagy/autophagy. Together, these three agents contribute to an accelerated aging program that can be averted by cellular NAD+ restoration.

BackgroundConcerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been raised. We studied whether use of NSAIDs was associated with adverse outcomes and mortality during SARS-CoV-2 infection.Methods and findingsWe conducted a population-based cohort study using Danish administrative and health registries. We included individuals who tested positive for SARS-CoV-2 during the period 27 February 2020 to 29 April 2020. NSAID users (defined as individuals having filled a prescription for NSAIDs up to 30 days before the SARS-CoV-2 test) were matched to up to 4 non-users on calendar week of the test date and propensity scores based on age, sex, relevant comorbidities, and use of selected prescription drugs. The main outcome was 30-day mortality, and NSAID users were compared to non-users using risk ratios (RRs) and risk differences (RDs). Secondary outcomes included hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and acute renal replacement therapy. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion. The median age in the study cohort was 50 years, and 58% were female. Of these, 248 (2.7%) had filled a prescription for NSAIDs, and 535 (5.8%) died within 30 days. In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82, p = 0.95; RD 0.1%, 95% CI −3.5% to 3.7%, p = 0.95), risk of hospitalization (RR 1.16, 95% CI 0.87 to 1.53, p = 0.31; RD 3.3%, 95% CI −3.4% to 10%, p = 0.33), ICU admission (RR 1.04, 95% CI 0.54 to 2.02, p = 0.90; RD 0.2%, 95% CI −3.0% to 3.4%, p = 0.90), mechanical ventilation (RR 1.14, 95% CI 0.56 to 2.30, p = 0.72; RD 0.5%, 95% CI −2.5% to 3.6%, p = 0.73), or renal replacement therapy (RR 0.86, 95% CI 0.24 to 3.09, p = 0.81; RD −0.2%, 95% CI −2.0% to 1.6%, p = 0.81). The main limitations of the study are possible exposure misclassification, as not all individuals who fill an NSAID prescription use the drug continuously, and possible residual confounding by indication, as NSAIDs may generally be prescribed to healthier individuals due to their side effects, but on the other hand may also be prescribed for early symptoms of severe COVID-19.ConclusionsUse of NSAIDs was not associated with 30-day mortality, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy in Danish individuals who tested positive for SARS-CoV-2.Trial registrationThe European Union electronic Register of Post-Authorisation Studies EUPAS34734