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  1. Article ; Online: Medication adherence-Key considerations for clinical pharmacologists.

    Hughes, Dyfrig A

    British journal of clinical pharmacology

    2020  Volume 86, Issue 4, Page(s) 628–629

    MeSH term(s) Humans ; Medication Adherence ; Physicians
    Language English
    Publishing date 2020-02-25
    Publishing country England
    Document type Editorial
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.14228
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  2. Article ; Online: Medication adherence research comes of age.

    Wright, Daniel F B / Sinnappah, Klarissa A / Hughes, Dyfrig A

    British journal of clinical pharmacology

    2023  Volume 89, Issue 7, Page(s) 1914–1917

    MeSH term(s) Humans ; Medication Adherence
    Language English
    Publishing date 2023-04-10
    Publishing country England
    Document type Editorial
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.15722
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  3. Article ; Online: Medicines Shortages in the United Kingdom.

    Hughes, Dyfrig A

    Clinical pharmacology and therapeutics

    2019  Volume 106, Issue 4, Page(s) 712

    MeSH term(s) Drug Industry ; Drug and Narcotic Control ; Drugs, Generic ; European Union ; Humans ; United Kingdom
    Chemical Substances Drugs, Generic
    Language English
    Publishing date 2019-06-25
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.1495
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  4. Article ; Online: Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam.

    Hughes, Dyfrig A

    British journal of pharmacology

    2020  Volume 177, Issue 21, Page(s) 4975–4989

    Abstract: Background and purpose: Resurgence in the use of chloroquine as a potential treatment for COVID-19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are ... ...

    Abstract Background and purpose: Resurgence in the use of chloroquine as a potential treatment for COVID-19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are uncertainties in its pharmacology and efficacy in this context. The aim was to assess the effects of diazepam in experimental models of chloroquine cardiotoxicity.
    Experimental approach: In vitro experiments involved cardiac tissues isolated from rats and incubated with chloroquine alone or in combination with diazepam. In vivo models of toxicity involved chloroquine administered intravenously to pentobarbitone-anaesthetised rats and rabbits. Randomised, controlled treatment studies in rats assessed diazepam, clonazepam and Ro5-4864 administered: (i) prior, (ii) during and (iii) after chloroquine and the effects of diazepam: (iv) at high dose, (v) in urethane-anaesthetised rats and (vi) co-administered with adrenaline.
    Key results: Chloroquine decreased the developed tension of left atria, prolonged the effective refractory period of atria, ventricular tissue and right papillary muscles, and caused dose-dependent impairment of haemodynamic and electrocardiographic parameters. Cardiac arrhythmias indicated impairment of atrioventricular conduction. Studies (i), (ii) and (v) showed no differences between treatments and control. Diazepam increased heart rate in study (iv) and as with clonazepam also prolonged the QTc interval in study (iii). Combined administration of diazepam and adrenaline in study (vi) improved cardiac contractility but caused hypokalaemia.
    Conclusion and implications: Neither diazepam nor other ligands for benzodiazepine binding sites protect against or attenuate chloroquine cardiotoxicity. However, diazepam may augment the effects of positive inotropes in reducing chloroquine cardiotoxicity.
    Linked articles: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.
    MeSH term(s) Animals ; Arrhythmias, Cardiac/chemically induced ; Arrhythmias, Cardiac/prevention & control ; Benzodiazepinones/pharmacology ; COVID-19 ; Cardiotoxicity/etiology ; Cardiotoxicity/prevention & control ; Chloroquine/poisoning ; Clonazepam/pharmacology ; Coronavirus Infections/drug therapy ; Diazepam/administration & dosage ; Diazepam/pharmacology ; Dose-Response Relationship, Drug ; Drug Overdose ; Electrocardiography ; Female ; Hypokalemia/chemically induced ; Male ; Pandemics ; Pneumonia, Viral/drug therapy ; Rabbits ; Random Allocation ; Rats ; Rats, Wistar
    Chemical Substances Benzodiazepinones ; 4'-chlorodiazepam (2QW0IK1742) ; Clonazepam (5PE9FDE8GB) ; Chloroquine (886U3H6UFF) ; Diazepam (Q3JTX2Q7TU)
    Keywords covid19
    Language English
    Publishing date 2020-06-18
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.15101
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  5. Article ; Online: Costs of orphan medicinal products

    Yankier Pijeira Perez / Eifiona Wood / Dyfrig A Hughes

    Orphanet Journal of Rare Diseases, Vol 18, Iss 1, Pp 1-

    longitudinal analysis of expenditure in Wales

    2023  Volume 8

    Abstract: Abstract Background The Orphan Regulation ((EC) No 141/2000) has successfully redirected private and public investment towards previously neglected areas through incentives, regulatory obligations and rewards. However, the growth in the number of ... ...

    Abstract Abstract Background The Orphan Regulation ((EC) No 141/2000) has successfully redirected private and public investment towards previously neglected areas through incentives, regulatory obligations and rewards. However, the growth in the number of licensed orphan medicinal products (OMPs) has led to concerns about increased costs. The aims were to investigate the trend in the costs of OMPs to the National Health Service in Wales, to attribute costs of medicines within and outside periods of marketing exclusivity, and estimate the contribution of individual medicines to the overall costs of OMPs. Methods Expenditure on OMPs in Wales was analysed between the 2014/15 and 2019/20 financial years using data on prescriptions dispensed in primary care, secondary care, and specialised commissioned services. OMP spend was calculated as a proportion of total medicines expenditure, whether it was incurred during, or outside the marketing exclusivity period (MEP), and by therapeutic area and medicine. Results Overall spend on OMPs and all medicines increased from £32 m to £82 m, and from £1,030 m to £1,198 m, respectively, with the proportion of spend on OMPs more than doubling from 3.1% to 6.9% per annum. Average year-on-year growth in the costs of OMPs was 21%, compared to 2% for other medicines. Costs following MEP expiry contributed significantly to overall OMP costs, increasing from £8 m to £30 m, corresponding to an increase from 24% to 37%. Treatments for ‘malignant disease and immunosuppression’, ‘nutrition and blood’ and the ‘respiratory system’ accounted for 90% of all OMP spend. Half of total OMP annual expenditure was on just 4 medicines in 2014/15, increasing to 8 in 2019/20. Conclusions Both the number of OMPs and the amount spent on OMPs in Wales has increased over time, possibly as a consequence of favourable licensing conditions, permissive health technology assessment policies and dedicated funding.
    Keywords Orphan Drugs ; Drug costs ; Costs analysis ; health economics ; Medicine ; R
    Subject code 941
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Costs of orphan medicinal products: longitudinal analysis of expenditure in Wales.

    Pijeira Perez, Yankier / Wood, Eifiona / Hughes, Dyfrig A

    Orphanet journal of rare diseases

    2023  Volume 18, Issue 1, Page(s) 342

    Abstract: Background: The Orphan Regulation ((EC) No 141/2000) has successfully redirected private and public investment towards previously neglected areas through incentives, regulatory obligations and rewards. However, the growth in the number of licensed ... ...

    Abstract Background: The Orphan Regulation ((EC) No 141/2000) has successfully redirected private and public investment towards previously neglected areas through incentives, regulatory obligations and rewards. However, the growth in the number of licensed orphan medicinal products (OMPs) has led to concerns about increased costs. The aims were to investigate the trend in the costs of OMPs to the National Health Service in Wales, to attribute costs of medicines within and outside periods of marketing exclusivity, and estimate the contribution of individual medicines to the overall costs of OMPs.
    Methods: Expenditure on OMPs in Wales was analysed between the 2014/15 and 2019/20 financial years using data on prescriptions dispensed in primary care, secondary care, and specialised commissioned services. OMP spend was calculated as a proportion of total medicines expenditure, whether it was incurred during, or outside the marketing exclusivity period (MEP), and by therapeutic area and medicine.
    Results: Overall spend on OMPs and all medicines increased from £32 m to £82 m, and from £1,030 m to £1,198 m, respectively, with the proportion of spend on OMPs more than doubling from 3.1% to 6.9% per annum. Average year-on-year growth in the costs of OMPs was 21%, compared to 2% for other medicines. Costs following MEP expiry contributed significantly to overall OMP costs, increasing from £8 m to £30 m, corresponding to an increase from 24% to 37%. Treatments for 'malignant disease and immunosuppression', 'nutrition and blood' and the 'respiratory system' accounted for 90% of all OMP spend. Half of total OMP annual expenditure was on just 4 medicines in 2014/15, increasing to 8 in 2019/20.
    Conclusions: Both the number of OMPs and the amount spent on OMPs in Wales has increased over time, possibly as a consequence of favourable licensing conditions, permissive health technology assessment policies and dedicated funding.
    MeSH term(s) Humans ; Rare Diseases/drug therapy ; Health Expenditures ; Wales ; State Medicine ; Orphan Drug Production
    Language English
    Publishing date 2023-11-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2225857-7
    ISSN 1750-1172 ; 1750-1172
    ISSN (online) 1750-1172
    ISSN 1750-1172
    DOI 10.1186/s13023-023-02956-3
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  7. Article ; Online: Impact of Relaxing Covid-19 Social Distancing Measures on Rural North Wales: A Simulation Analysis.

    Hughes, Rhodri P / Hughes, Dyfrig A

    Frontiers in public health

    2020  Volume 8, Page(s) 562473

    Abstract: Background: ...

    Abstract Background:
    MeSH term(s) COVID-19/epidemiology ; COVID-19/mortality ; Communicable Disease Control ; Computer Simulation ; England/epidemiology ; Government ; Humans ; Physical Distancing ; Population Density ; Rural Population ; Wales/epidemiology
    Language English
    Publishing date 2020-12-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2711781-9
    ISSN 2296-2565 ; 2296-2565
    ISSN (online) 2296-2565
    ISSN 2296-2565
    DOI 10.3389/fpubh.2020.562473
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  8. Article ; Online: Economics of Pharmacogenetic-Guided Treatments: Underwhelming or Overstated?

    Hughes, Dyfrig A

    Clinical pharmacology and therapeutics

    2018  Volume 103, Issue 5, Page(s) 749–751

    Abstract: Economic evaluations have dispelled a perception that precision medicine, achieved through pharmacogenetic testing, reduces healthcare costs. For many tests aimed at preventing adverse drug reactions, cost-effectiveness analyses predict modest ... ...

    Abstract Economic evaluations have dispelled a perception that precision medicine, achieved through pharmacogenetic testing, reduces healthcare costs. For many tests aimed at preventing adverse drug reactions, cost-effectiveness analyses predict modest improvements in health benefits and increases in total costs. While there are many uncertainties in estimating the value of testing, factors that influence cost-effectiveness include the rarity of the outcome, the effectiveness of alternative treatments, and the scope and perspective of analysis.
    MeSH term(s) Cost-Benefit Analysis/economics ; Health Care Costs ; Humans ; Pharmacogenetics/economics ; Pharmacogenomic Testing/economics ; Precision Medicine/economics
    Language English
    Publishing date 2018-02-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.1030
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  9. Article ; Online: Pharmacogenomics spotlight commentary: From the United Kingdom to global populations.

    Magavern, Emma F / Daly, Ann K / Gilchrist, Annette / Hughes, Dyfrig A

    British journal of clinical pharmacology

    2021  Volume 87, Issue 12, Page(s) 4546–4548

    MeSH term(s) Humans ; Pharmacogenetics ; United Kingdom
    Language English
    Publishing date 2021-05-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.14917
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  10. Article: Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam

    Hughes, Dyfrig A

    Br. j. pharmacol

    Abstract: BACKGROUND AND PURPOSE: Resurgence in the use of chloroquine as a potential treatment for COVID-19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are ... ...

    Abstract BACKGROUND AND PURPOSE: Resurgence in the use of chloroquine as a potential treatment for COVID-19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are uncertainties in its pharmacology and efficacy in this context. The aim was to assess the effects of diazepam in experimental models of chloroquine cardiotoxicity. EXPERIMENTAL APPROACH: In vitro experiments involved cardiac tissues isolated from rats and incubated with chloroquine alone or in combination with diazepam. In vivo models of toxicity involved chloroquine administered intravenously to pentobarbitone-anaesthetised rats and rabbits. Randomised, controlled treatment studies in rats assessed diazepam, clonazepam and Ro5-4864 administered: (i) prior, (ii) during and (iii) after chloroquine and the effects of diazepam: (iv) at high dose, (v) in urethane-anaesthetised rats and (vi) co-administered with adrenaline. KEY RESULTS: Chloroquine decreased the developed tension of left atria, prolonged the effective refractory period of atria, ventricular tissue and right papillary muscles, and caused dose-dependent impairment of haemodynamic and electrocardiographic parameters. Cardiac arrhythmias indicated impairment of atrioventricular conduction. Studies (i), (ii) and (v) showed no differences between treatments and control. Diazepam increased heart rate in study (iv) and as with clonazepam also prolonged the QTc interval in study (iii). Combined administration of diazepam and adrenaline in study (vi) improved cardiac contractility but caused hypokalaemia. CONCLUSION AND IMPLICATIONS: Neither diazepam nor other ligands for benzodiazepine binding sites protect against or attenuate chloroquine cardiotoxicity. However, diazepam may augment the effects of positive inotropes in reducing chloroquine cardiotoxicity.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #32415690
    Database COVID19

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