David Millson

Objective The primary objectives of two phase II studies of fostamatinib were to evaluate efficacy (OSKIRA-Asia-1: NCT01569074) and long-term safety/tolerability (OSKIRA-Asia-1X: NCT01640054) in patients from Asia with active RA despite MTX treatment. Methods OSKIRA-Asia-1 was a 12-week, multicentre, double-blind, placebo-controlled, parallel-grou...

SUM M AR Y Radioligand binding techniques, employing H-(-)-dihydroalprenolol 3H ( H-DHA) , a competitive antagonist at the Beta-adrenoceptor were used to develop a reliable, sensitive, quantitative _in vitro method to study Beta-adrenoceptor number and affinity in animal and human tissues, with particular reference to the cardiac Beta-adrenoceptor....

TITLE: "PHARMACODYNAMIC RESPONSES OF 5-HT2 ANTAGONISTS AS AN AID TO DRUG DEVELOPMENT IN MAN." CANDIDATE. DAVID STEVEN MILLSON BSc(Hons). ,MB. .BChir.,PhD. SUMMARY. Digitised 9th Oct 2018 The aims of this thesis were to describe the clinical pharmacology of two 5-hydroxytryptamine type 2 (5-HT2) receptor antagonists being developed for cardiovascul...

Background Fostamatinib (R788) is a spleen tyrosine kinase (SYK) inhibitor. The active metabolite of fostamatinib, R406, is primarily metabolized by CYP3A4. Objectives The aim of this study was to characterize hepatic microsomal metabolism of R406 and confirm the role of CYP3A4 in R406 metabolism, determining whether co-administration of CYP3A4 inh...

Fostamatinib is a prodrug that undergoes gastrointestinal tract dephosphorylation to form the active metabolite, R406. Here we report its cytochrome P450-inducing potential. In vitro, R406 3 and 10 μM induced CYP2C8 to levels representing 53% and 75%, respectively, of the level achieved by the positive control, rifampicin. Induction of other enzyme...

Purpose: Phase III trials of fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis have been completed. Herein, we report the effects of renal and hepatic impairment on the pharmacokinetic (PK) properties of the active metabolite of fostamatinib, R406, in plasma, and on the urinary excretion of R406 and i...

Purpose: Fostamatinib, a spleen tyrosine kinase inhibitor and prodrug of the active metabolite R406, is being developed as an anti-inflammatory drug for several indications for which polypharmacy is likely. Digoxin, indicated for congestive cardiac failure, may be used for certain supraventricular dysrhythmias. The studies reported herein examined...

Objective: This phase III, 52-week study compared fostamatinib with placebo (for 24 weeks) in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) therapy. Methods: Patients taking MTX were randomized (1:1:1) to receive fostamatinib 100 mg twice daily for 52 weeks (group A), fostamatinib 100 mg twice da...

Background Fostamatinib (R788), a spleen tyrosine kinase inhibitor, is currently being developed as an oral therapy for patients with rheumatoid arthritis1. In humans, orally administered fostamatinib is converted to the active moiety, R406. Elimination into the urine accounts for 19% of the administered dose (<1% of dose is excreted as R406 in uri...

A survey was used to examine headache experiences and related health care use in an adult population Almost half of older respondents reported headache in the previous three months compared with four-fifths of younger respondents Older headache sufferers reported headache as frequently as younger sufferers but of shorter duration and less painful M...

The objective of this study was to determine predictors of onset of new headache episodes and recovery from headache over one year. A population-based cohort study was conducted, comprising a baseline postal survey to a random sample of adults aged>or=18 years, with follow-up survey after 1 year. Risk factor data at baseline were compared with head...

Editor—I write with reference to the paper by Junghans et al on recruiting patients to medical research.1 We recently published a method to determine if consenters to population surveys are representative of the target study population.2 Recently introduced data protection legislation has changed research practice in the United Kingdom, although u...

To quantify the relation between substance misuse and psychiatric illness in the UK general practice population in terms of (a) the relative risk of developing one condition given prior exposure to the other and (b) the proportion of cases of one condition attributable to exposure to the other. Population based prospective observational study using...

To investigate the associations of headache occurrence, severity, and frequency with psychological, sleep, and lifestyle characteristics, and comorbid conditions. Whilst associations for individual headache types, particularly migraine, have been investigated, possible associations between headache of all types and general health characteristics ha...

Searching medical records of study non-responders to investigate selection bias is no longer acceptable. We explore an alternative by comparing consultation rates in survey responders who consented to medical record review, with anonymized consultation rates for the total practice populations. Anonymized aggregated consultation rates for the year f...

To investigate variation in headache occurrence and characteristics over 1 year. Headache is a common condition which can affect the work, home, and social lives of sufferers, yet surprisingly little is known about how headache changes over time. Postal survey to a random general population sample of 5000 adults aged 18 years plus, with follow-up s...

To estimate the annual period prevalence of co-occurring psychiatric illness and substance misuse among patients in primary care. Analysis of the general practice research database. England and Wales, 1993-1998. Registered patients at 230 general practices representing 3.1% of the population. A comorbid case was defined as one with both a psychiatr...

Using data from a cross-sectional survey and a prospective record linkage study the aims of this study were to: (i) determine sources of advice and care for headaches in a population survey of adults, and (ii) investigate prospectively the influences of headaches on general practice consultation in a 12-month follow-up of the responders to the popu...

To evaluate the comparative efficacy and tolerability of naratriptan in the treatment of acute attacks of migraine. Meta-analysis of randomised controlled trials using a random effects model. A total of 4499 patients suffering from moderate or severe attacks of acute migraine reported in ten trials. Response rate ratios for headache relief, pain-fr...

The potential of the General Practice Research Database (GPRD) for communicable disease surveillance was explored using head lice as an example. All diagnoses of head lice and prescriptions for parasiticidal agents from 1993 to 2000 in the West Midlands were analysed. Diagnoses reached a peak of 28.2 per 1,000 patient years at risk and total prescr...

The North Staffordshire Headache Survey aims to measure the effect and impact of headaches, medicine use and healthcare utilization in a general population sample. A self-reporting questionnaire was piloted in a general population sample, with reliability being tested in a sample of pilot responders after one month and validity by comparing pilot r...

The triptans are 5-HT(1B/1D) agonists used as migraine and cluster-specific agents. Seven are in commercial use worldwide; in order of release these are sumatriptan, zolmitriptan, rizatriptan, naratriptan, almotriptan, frovatriptan and eletriptan. Sumatriptan has been in clinical use since 1991, and although postmarketing studies have stimulated mu...

Headache prevalence, characteristics and impact in adults were measured using a cross-sectional general population survey in North Staffordshire, UK. A postal survey was mailed out to 4885 adults (aged > or = 18 years) with an adjusted response rate of 56% (n = 2662). Of respondents 93% reported headache ever and 70% in the last 3 months. Women and...

Objectives - To investigate the use of over-the-counter sleep aids purchased from community pharmacies in order to establish a demographic profile of users, determine the extent of any inappropriate use, and test the feasibility of community pharmacy-based data collection from medicines users. Design - Pre-piloted self-completion questionnaire. Pha...

Background: The Disability in Strategies for Care (DISC) study was the first large randomised controlled trial to compare alternative treatment strategies in the acute treatment of migraine. With 835 patients in its intention-to-treat efficacy analysis, DISC compared a stratified care strategy, where initial therapy was based on clinical need as d...

A survey was used to examine headache experiences and medication use in an adult population sample □ Seventy per cent had experienced headaches in the previous three months □ Sixty per cent had taken medication for headache in the past three months □ Most headache sufferers self-treated their headaches □ Only a few respondents had taken medication...

To evaluate the comparative incidence of endoscopic gastroduodenal ulcers in patients with rheumatoid arthritis or osteoarthritis treated with celecoxib. Quantitative systematic review of randomized controlled trials. Patients (n = 4632) with rheumatoid arthritis or osteoarthritis reported in five trials. Rate ratios, rate differences, and the numb...

This randomized, double-blind, parallel-group study compared the efficacy and tolerability of zolmitriptan (2.5 or 5 mg) and sumatriptan (50 mg) in the acute oral treatment of up to six moderate-to-severe migraine attacks. The intention to treat (ITT) population comprised of 1522 patients: 500 treated with zolmitriptan 2.5 mg (2671 attacks), 514 wi...

Recent concerns that evidence on the appropriate use of antibiotics is not having an impact on prescribing trends are based on UK prescribing data relating to 1980-1991. The aim of this paper is to determine trends in antibiotic prescribing from 1993 to 1997 and link antibiotic prescriptions to diagnostic categories. A retrospective analysis of ant...

1997, sumatriptan-treated migraineurs had significantly higher depression PCRs (22.3%) compared with non-triptan users (19.3%), a difference of 6.4% (95% confidence interval (CI) 4.6-8.4%, P < 0.001). In the year (April 1997 to March 1998) following the launch of the TELs, depression PCRs were significantly higher among patients using these compoun...

Regional Drug Misuse Databases (RDMDs) are considered the main source of intelligence on problem drug takers in England. Originally intended to provide trend data on visible drug use, a recent strategic review concluded that their purpose should be to monitor treatment targets for the Government's latest 10 year strategy to tackle drug misuse. The...

To evaluate the efficacy and tolerability of oral zolmitriptan 5 mg and 10 mg and placebo in cluster headache. A multicenter, double-blind, randomized, three-period, crossover, outpatient study. Adult patients received placebo and zolmitriptan 5 mg and 10 mg orally for the acute treatment of episodic or chronic cluster headache. Headache intensity...

The recent clinical development of a number of migraine specific 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs), relative to the first drug of this class sumatriptan, and with a range of different metabolic, pharmacokinetic and receptor affinity profiles, provides the potential for critically different clinical profiles. Eletriptan,...

A Delphi exercise was undertaken to develop the curriculum in pharmaceutical medicine necessary for each advanced training module that will lead to the award of a Certificate of Completion of Specialist Medical Training. The Delphi exercise used a panel for each module to identify the range of competencies and define the knowledge and skills requir...

In the last two years, a number of 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs) relative to the first drug of this class, sumatriptan, have been approved for marketing in most countries of the world (naratriptan, rizatriptan and zolmitriptan). In addition, at least three others are in advanced stage of clinical development (almotri...

The key objective of clinical governance in relationship to prescribing should be to optimise the use of the evidence base for medicines to ensure that cost issues do not over-ride the quality agenda and that health gain for patients remains the focus of the prescribing agenda. As most medicines are dispensed through primary care, a key considerati...

A Delphi exercise were undertaken to develop the curriculum in pharmaceutical medicine necessary for each advanced training module that will lead to the award of a Certificate of Completion of Specialist Medical Training. The Delphi exercise used a panel for each module to identify the range of competencies and define the knowledge and skills requi...

Previous research based on aggregated data has led to conflicting interpretations of the relationship between the corticosteroid:bronchodilator (C:B) ratio and outcome measures. To assess whether the C:B ratio is associated with hospital contact for asthma at individual patient level. The study was a retrospective multivariate analysis, using data...

In recent years the ratio of inhaled corticosteroid:bronchodilator (C:B) prescribing has been promoted as a quality marker for asthma treatment and cross-sectional data indicate an association with hospital admissions. If prescribing advice has been followed then it can be hypothesised that the C:B ratio will have increased and hospitalisation decr...

Part 1 of this international study was a randomised, double-blind, placebo-controlled study of 2.5 mg and 5 mg zolmitriptan (Zomig) in the treatment of persistent migraine headache, two hours after an initial dose of 2.5 mg zolmitriptan. Part 2 was a non-comparative evaluation of long-term, unrestricted zolmitriptan use for treatment of initial, pe...

Editor—The clinical research edition of the 13 June issue of the BMJ contained an advertisement for Didronel PMO (between pages 1764 and 1765). The advertisement claimed that the combination tablet of disodium etidronate 400 mg and calcium carbonate 1250 mg “is proven and licensed to protect bones from corticosteroid induced osteoporosis.” However,...

A Delphi exercise was undertaken to develop the curriculum in pharmaceutical medicine necessary for each advanced training module that will lead to the award of a Certificate of Completion of Specialist Medical Training. The Delphi exercise used a panel for each module to identify the range of competencies and define the knowledge and skills requir...

A Delphi exercise were undertaken to develop the curriculum in pharmaceutical medicine necessary for each advanced training module that will lead to the award of a Certificate of Completion of Specialist Medical Training. The Delphi exercise used a panel for each module to identify the range of competencies and define the know-ledge and skills requ...

Sumatriptan, the first and most extensively studied triptan was a significant therapeutic innovation delivering a high degree of within-patient consistency and robust efficacy with the subcutaneous formulation; with an extensive range of doses (5,10, 25, 50 and 100 mg) across a number of delivery systems (oral, intra-nasal and rectal). However suma...

Zolmitriptan (Zomig, formerly 311C90) at doses of 0.5-50 mg was administered to 316 unique volunteers in clinical pharmacology studies and 2,750 unique patients in eight clinical studies of acute migraine treatment. Overall, subjects received almost 50,000 doses; 97% of exposures were at doses > or = 2.5 mg. In the clinical pharmacology studies, th...

1. ICI 170,809 (2-(2-dimethylamino-2-methylpropylthio)-3-phenylquinoline hydrochloride) is a potent 5-hydroxytryptamine (5-HT) type 2 postsynaptic receptor antagonist. 2. Effects of ICI 170,809 as single oral doses (3, 7, 15 and 30 mg) or placebo were studied on the duration of antagonism for the ex vivo platelet aggregatory response to 5-HT and to...

1. ICI 169,369 (2-(2-dimethylamino ethylthio)-3-phenyl quinoline) is a potent selective competitive antagonist of the 5-HT2 receptor in animal models. Effects of ICI 169,369 as single oral doses (80 and 120 mg) separated by 1 week, on the power spectrum of waking EEG, dark adapted pupil responses and sedation score, were studied in a double-blind,...

We have assessed the ability of doppler echocardiography, both continuous and pulsed wave, to measure changes in cardiac function in human volunteers following dobutamine infusions. Changes in peak velocity and stroke distance were measured in the ascending aorta by angulating a 2 mHz (Vingmed) carrier probe in the suprasternal notch and analysing...

Thymocytes have been studied at various stages during ontogeny in relation to their responsiveness to β adrenoceptor agonists and ability to bind L-[propyl-2,3-3H]dihy-droalprenolol ([3H]DHA), a specific radioligand of the β adrenoceptor. Specific [3H]DHA binding and the activity of an isoproterenol-sensitive adenylate cyclase were compared and cor...

Thesis (Ph. D.)--University of Newcastle upon Tyne, 1981.

Thesis (Ph. D.)--University of Newcastle upon Tyne. 1981. British Library microfilm no.: D40984/82.