Use of direct oral anticoagulants in patients with atrial fibrillation in Scotland : applying a coherent framework to drug utilisation studies

Purpose: To report the use of direct oral anticoagulants (DOAC) for stroke prevention in patients with atrial fibrillation (AF) in Scotland and advocate the standardisation of drug utilisation research methods. Methods: Retrospective cohort study using linked administrative data. Patients included those with a diagnosis of AF (confirmed in hospital) who received a first prescription for a DOAC (dabigatran, rivaroxaban, apixaban) from September 2011 to June 2014. Drug utilisation measures included discontinuation, persistence, and adherence. Results: 5398 patients (mean CHA2DS2-VASc score 2.98 [SD 1.71], 89.7% with ≥ 6 concomitant medicines) were treated with DOACs for a median of 228 days (IQR 105 – 425). Of 35.6% who discontinued DOAC treatment, 11.0% switched to warfarin and 48.3% re-initiated DOACs. Persistence after 12 and 18 months were 75.9% and 69.8%, respectively. Differences between individual DOACs were observed: discontinuation rates ranged from 20.4% (apixaban) to 60.6% (dabigatran), and 12 months persistence from 60.1% (dabigatran) to 85.5% (apixaban). Adherence to treatment with all DOACs was good: overall DOAC median medication refill adherence (MRA) was 102.9% (IQR 88.9% – 115.5%), and 82.3% of patients had an MRA > 80%. Conclusions: In Scotland, adherence to DOAC treatment was good and switching from DOAC to warfarin was low. However, discontinuation and persistence rates were variable – although treatment interruptions were often temporary. To decrease the inconsistencies in drug utilisation methods and facilitate meaningful study comparison, the use of a coherent framework – using a combination of discontinuation, persistence and adherence – and the standardisation of measurements is advocated

The Chihuahua sustainability practice: lots of shivering but no real action. Practical sustainability acceptance is low in German and New Zealand firms

Purpose &ndash; This paper aims to describe the extent to which corporate organizations in Germany and in New Zealand have included sustainability practices as part of their strategic planning process.Design/methodology/approach &ndash; Current literature is reviewed to make a case for sustainability to be a driver behind corporate decision making and long-term performance. The results of surveys of several hundred firms in both Germany and New Zealand, countries with a publicly stated commitment to sustainability, are reviewed to compare the adoption rates of sustainability practices.Findings &ndash; There is a significant difference between what firms do and what their managers think is important. Managers largely consider sustainability practices an important factor for their future careers, while firms to a large extent do not include sustainability as part of their strategic or operational planning process.Research limitations/implications &ndash; The International Sustainability Acceptance Measurement (ISAM) collects data in several countries through local-language versions of the same online survey tool (www.worldreply.com). The findings in this report are specific only to New Zealand and Germany.Practical implications &ndash; The paper points academics, corporate executives and sustainability fanatics to an alarming inconsistency between what is publicly reported as commitment to sustainability and what is practically achieved.Originality/value &ndash; This paper adds value to the discussion of how sustainability practices have migrated into the operation of firms.<br /

Bayesian hierarchical approaches for multiple outcomes in routinely collected healthcare data

Background: Routinely collected healthcare data provides a rich environment for the investigation of drug performance in the general population, while also offering the possibility of assessing rare outcomes. The statistical analysis of this data poses a number of challenges. The data may be biased and lack the structure and balance provided by the drugs’ clinical trials. Outcomes are often modelled individually with an associated lack of control for multiple comparisons, as well as a difficulty in assessing multiple risks. Methods: Bayesian models provide methods for analysing multiple clinical outcomes, using relationships between outcomes and handling the types of multiple comparison issues which may occur when using multiple single-variate approaches. Lack of balance within the data may be catered for by dividing the population into clusters with similar characteristics, allowing within cluster inferences to be made. A Bayesian hierarchical model for multiple outcomes is proposed and applied to data from a safety and effectiveness study of direct oral anticoagulants (DOACs) in Scotland 2009 – 2015. Results: The Bayesian modelling results were comparable to the results from the original safety and effectiveness study, with the additional benefit of balancing patient clusters and controlling for relationships in the data. Conclusion: Bayesian hierarchical models are a suitable approach for modelling routinely collected healthcare data. There is the possibility of moving to an integrated Bayesian approach, with the inclusion of treatment relationships; uncertainty regarding cluster membership; and treatment allocation in the model, eventually leading to more reliable treatment decisions

the role of firms

Der Standortwechsel von Firmen in Länder mit niedrigen Sozialstandards wird in der Regel als treibende Kraft des abwärtsgerichteten regulativen Wettbewerbs zwischen Staaten angesehen. Es gibt allerdings eine Vielzahl von Fällen in denen genau das Gegenteil passiert: Firmen halten sich freiwillig an Sozialstandards (CSR) und üben sogar Druck auf Regierungen aus, um striktere Regulierung zu erwirken. In diesem Arbeitspapier zeigen wir, unter welchen Bedingungen Firmen zur Verwirklichung anspruchsvollerer Sozialstandards in Ländern mit geringer regulativer Kapazität beitragen. Zunächst stellen wir Hypothesen aus der bereits existierenden Literatur vor und arbeiten ihre Erklärungskraft für die hier diskutierte Problematik heraus. Das Arbeitspapier untersucht die Reaktion der südafrikanischen Textil- und Automobilindustrie auf die HIV Pandemie. Die südafrikanische Regierung hat nur begrenzte Kapazitäten aufgebracht, um sich gegen die Verbreitung des Virus zur Wehr zu setzen. Unter welchen Bedingungen versuchen Firmen den Staat im Kampf gegen HIV/AIDS zu unterstützen?Firms relocating production to countries with lower social standards are regarded as driving force behind the regulatory ‘race to the bottom’. However, there are numerous instances in which the behavior of firms reveals just the opposite: They adhere to self-regulatory standards (CSR) and even pressure governments to issue stricter public regulations. We intend to identify the conditions under which firms contribute to higher regulatory standards in states with weak regulatory capacities, thereby following a ‘race to the top’ rather than a ‘race to the bottom’- logic. Theoretically, we set out to test in how far the existing literature can be utilized to answer this question. Empirically, the assessment concentrates on the textile and automotive industries in South Africa and HIV/AIDS abatement. Only limited state capacities have been involved in fighting HIV/AIDS in South Africa. Under which conditions do firms try to foster state capacities for the fight against the disease

Comparative safety and effectiveness of direct oral anticoagulants in patients with atrial fibrillation in clinical practice in Scotland

To compare the clinical effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) in routine clinical practice. Retrospective cohort study using linked administrative data. The study population (n=14,577) included patients with a diagnosis of AF (confirmed in hospital) who initiated DOAC treatment in Scotland between August 2011 and December 2015. Multivariate Cox proportional hazard models were used to estimate hazard ratios of thromboembolic events, mortality, and bleeding events. No differences between the DOACs were observed in the risks of stroke, systemic embolism, or cardiovascular death. In contrast, the risk of myocardial infarction was higher among apixaban patients in comparison to rivaroxaban (1.67 [1.02 - 2.71]), and all-cause mortality was higher among rivaroxaban patients in contrast to both apixaban (1.22 [1.01 - 1.47]) and dabigatran (1.55 [1.16 - 2.05]); rivaroxaban patients also had a higher risk of pulmonary embolism than apixaban patients (5.27 [1.79 - 15.53]). The risk of other major bleeds was higher among rivaroxaban patients compared to apixaban (1.50 [1.10 - 2.03]) and dabigatran (1.58 [1.01 - 2.48]); the risks of gastro-intestinal bleeds and overall bleeding were higher among rivaroxaban patients than among apixaban patients (1.48 [1.01 - 2.16] and 1.52[1.21 - 1.92], respectively). All DOACs were similarly effective in preventing strokes and systemic embolisms, while patients being treated with rivaroxaban exhibited the highest bleeding risks. Observed differences in the risks of all-cause mortality, myocardial infarction, and pulmonary embolism warrant further research. [Abstract copyright: This article is protected by copyright. All rights reserved.

What does Twitter say about COVID-19 vaccines?

Background and objectives: Vaccines to reduce the level of hospitalisations and death from COVID-19 became available in certain countries from December 2020. This study aimed to analyse social media content shared on Twitter regarding COVID-19 vaccines on a random day to obtain insights into publicly expressed opinions on these vaccines. Method: English language tweets, regardless of country of origin, were collected through NCapture from a 24-hour time period between 06/11/2022 and 07/11/2022 using the search term “COVID-19 vaccines”. NVivo aided content analysis was conducted on all obtained tweets; tweets unrelated to the study aim were coded as irrelevant and subsequently excluded from analysis. The study was exploratory in nature, without an underlying hypothesis. Results: Overall, 1284 tweets were captured. A total of 67 different codes were created with 50 of those directly relating to opinions and/or information about COVID-19 vaccines; 41.8% of which were negative and 34.3% positive. Positive tweets related to, e.g., encouraging the public to get the vaccine; reductions in COVID-19 related health burdens; and providing links to scientific studies. In contrast, negative tweets warned of potential dangers associated with vaccines, primarily highlighting side effects; and reiterated prevalent conspiracy theories. Conclusion: Overall, opinions on Twitter regarding COVID-19 vaccines showed considerable variation on the day the tweets were captured. Nevertheless, there was a notable number of tweets providing links to reliable studies on COVID-19 vaccines, indicating that many Twitter users may aim to provide reliable information regarding COVID-19 vaccines

An umbrella review and quality assessment of renin-angiotensin system drugs use and Covid-19 outcomes : wat is the quality of the research evidence?

Background: During 2020, an extensive number of reviews were published on the effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) on COVID-19 outcomes, yet the evidence appeared heterogenous. We conducted a meta-analysis and quality assessment of these reviews. Methods: An umbrella review was conducted. Medline, Embase, Scopus, Cochrane library and medRxiv were searched on 1 February 2021. The AMSTAR 2 Critical Appraisal Tool assessed study quality. The Corrected Cover Area (CCA) calculated the degree of study overlap within the reviews. Results: In 2020/21, 47 reviews on this topic were conducted. The overall confidence in the results was most commonly ‘critically low’ (n=22, 44.9%), followed by ‘low’ (n=15, 30.6%) and ‘moderate’ (n=10, 21.3%). A minority (n=15, 31.9%) established a review protocol a priori. The CCA value was 9.2 indicating a moderate degree of study overlap, yet this analysis was complicated by three studies not fully reporting included studies. In total, 168 studies were known to have been included within the reviews. Most (n = 99) were included in three or less reviews, yet one study was included within 37 reviews. Collective evidence indicated good quality evidence on the significant association between ACEIs/ARBs use and reduction in death and death/ICU admission, but poor-quality evidence on reducing severe COVID-19 and increasing hospitalisation. Conclusions: The superfluous research activities are likely related to the collective interest in the topic, and limited development of review protocols a-priori. Despite quality concerns, our findings do support not discontinuing ACEIs/ARBs therapy in patients with COVID-19

An umbrella review and meta-analysis of renin-angiotensin system drugs use and COVID-19 outcomes

Abstract: Background: Despite the availability of extensive literature on the effect of angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin‐receptor blockers (ARBs) on COVID‐19 outcomes, the evidence is still controversial. We aimed to provide a comprehensive assessment of the effect of ACEIs/ARBs on COVID‐19‐related outcomes by summarising the currently available evidence. Methods: An umbrella review was conducted using Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 1 February 2021. Systematic reviews with meta‐analysis that evaluated the effect of ACEIs/ARBs on COVID‐19‐related clinical outcomes were eligible. Studies' quality was appraised using the AMSTAR 2 Critical Appraisal Tool. Data were analysed using the random‐effects modelling including several subgroup analyses. Heterogenicity was assessed using I2 statistic. The study protocol was registered in PROSPERO (CRD42021233398) and reported using PRISMA guidelines. Results: Overall, 47 reviews were eligible for inclusion. Out of the nine COVID‐19 outcomes evaluated, there was significant associations between ACEIs/ARBs use and each of death (OR = 0.80, 95%CI = 0.75–0.86; I2 = 51.9%), death/ICU admission as composite outcome (OR = 0.86, 95%CI = 0.80–0.92; I2 = 43.9%), severe COVID‐19 (OR = 0.86, 95%CI = 0.78–0.95; I2 = 68%) and hospitalisation (OR = 1.23, 95%CI = 1.04–1.46; I2 = 76.4%). The significant reduction in death/ICU admission, however, was higher among studies which presented adjusted measure of effects (OR = 0.63, 95%CI = 0.47–0.84) and were of moderate quality (OR = 0.74, 95%CI = 0.63–0.85). Conclusions: Collective evidence from observational studies indicate a good quality evidence on the significant association between ACEIs/ARBs use and reduction in death and death/ICU admission, but poor‐quality evidence on both reducing severe COVID‐19 and increasing hospitalisation. Our findings further support the current recommendations of not discontinuing ACEIs/ARBs therapy in patients with COVID‐19

The real-world use of drugs for the management of cancer in pediatric population : a scoping review protocol

Objective: The objective of the forthcoming scoping review is to investigate and describe the actual management of pediatric cancer patients who access various clinical settings. Introduction: The overall cancer management with the aid of drugs is a multifaceted process to treat the diagnosed patients, which is usually along with another treatment modalities. This process also involves controlling the emerged harmful symptoms attributed to cancer or cancer treatment using drugs in an effort to enhance patients’ experience during treatment course and improve their quality of life, besides avoiding the long-lasting detrimental clinical impact. Inclusion criteria: All observational studies that focus on the use of drugs in cancer patients age

Enzyme-functionalized biomimetic apatites: concept and perspectives in view of innovative medical approaches

Biomimetic nanocrystalline calcium-deficient apatite compounds are particularly attractive for the setup of bioactive bone-repair scaffolds due to their high similarity to bone mineral in terms of chemical composition, structural and substructural features. As such, along with the increasingly appealing development of moderate temperature engineered routes for sample processing, they have widened the armamentarium of orthopedic and maxillofacial surgeons in the field of bone tissue engineering. This was made possible by exploiting the exceptional surface reactivity of biomimetic apatite nanocrystals, capable of easily exchanging ions or adsorbing (bio)molecules, thus leading to highly-versatile drug delivery systems. In this contribution we focus on the preparation of hybrid materials combining biomimetic nanocrystalline apatites and enzymes (lysozyme and subtilisin). This paper reports physico-chemical data as well as cytotoxicity evaluations towards Cal-72 osteoblast-like cells and finally antimicrobial assessments towards selected strains of interest in bone surgery. Biomimetic apatite/enzyme hybrids could be prepared in varying buffers. They were found to be non-cytotoxic toward osteoblastic cells and the enzymes retained their biological activity (e.g. bond cleavage or antibacterial properties) despite the immobilization and drying processes. Release properties were also examined. Beyond these illustrative examples, the concept of biomimetic apatites functionalized with enzymes is thus shown to be useable in practice, e.g. for antimicrobial purposes, thus widening possible therapeutic perspectives