25 results on '"Thomas, S. H."'
Search Results
2. Thinking outside the square: Evidence that plot shape and layout in forest inventories can bias estimates of stand metrics.
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Paul, Thomas S. H., Kimberley, Mark O., Beets, Peter N., and Yoccoz, Nigel
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ACQUISITION of data ,FORESTS & forestry ,ECOLOGY ,BIOMASS ,CARBON - Abstract
Plot‐based data collection is an important component of quantitative ecological research and is widely used. Some of the most extensive plot‐networks can be found in country‐wide forest inventories, which provide critical information about the state of forest ecosystems. While sampling designs for forest inventories have been well studied, plot design and installation has received less attention.The New Zealand National Forest Inventory of natural forest uses a nested plot design with a 0.126 ha circular plot superimposed concentrically on a 0.04 ha square plot. Stems ≥ 60 cm diameter at breast height (DBH) are measured in the circular plot while stems ≥ 2.5 DBH are measured in the square plot. Stem density of ≥60 cm DBH stems measured in the circular plots were compared with those from square plots.Stem densities estimated from square plot measurements were 23.7% higher than those estimated from circular plot measurements in the 2002–2007 inventory, and 18.4% higher in the 2009–2014 inventory. The main cause of this discrepancy appears to be due to the placement of plot boundaries during establishment of square plots. This effect may have resulted from a subconscious tendency of field teams to include large trees inside plots when laying out these boundaries. It is concluded that estimates from the circular plots are unlikely to be biased while those from the square plots are positively biased.This study highlights the critical importance of plot design and plot placement in forest inventories to ensure that estimates of stand attributes are unbiased. Especially on undulating or uneven terrain, methods of determining whether trees are inside or outside plot boundaries of circular plots are likely to be more accurate than those typically used for square or rectangular plots. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
3. Using poisons information service data to assess the acute harms associated with novel psychoactive substances.
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Wood, D. M., Hill, S. L., Thomas, S. H. L., and Dargan, P. I.
- Abstract
Novel psychoactive substances (NPS) can cause significant acute toxicity but usually little is known about their toxicity when they enter the recreational drug scene. Current data sources include online user forums, user questionnaires, case reports/series, and deaths; however, these are limited by their focus on sub-populations and generally include severe cases and specific geographical areas. Approximately 54% of countries have at least one poisons information service (in 2012 there were 274 worldwide) providing advice to healthcare professionals and/or the public on poisoning. They provide advice on recreational drug and NPS toxicity. In 2012, 2.5% of telephone enquiries to the UK National Poisons Information Service and 2.4% of enquiries to US poisons centres related to recreational drugs. Data are collected at population level and can be used to complement other data sources with clinical details on acute NPS toxicity and geographical/time patterns of toxicity. Like other acute NPS toxicity data, poisons centre data should be interpreted within their limitations, notably the absence of analytical confirmation and reliance on secondary reporting of clinical features. This manuscript demonstrates the breadth and depth of poisons information service data in the literature with a focus on mephedrone and synthetic cannabinoid-receptor agonists. In our opinion it would be possible to develop a more robust and systematic reporting system using a network of poisons information services both within and across countries that would be complimentary to other datasets on acute NPS toxicity and allow more accurate data triangulation. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
4. Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP).
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Thomas, S. H. L., Drici, M. D., Hall, G. C., Crocq, M. A., Everitt, B., Lader, M. H., Jeunne, C. Le., Naber, D., Priori, S., Sturkenboom, M., Thibaut, F., Peuskens, J., Mittoux, A., Tanghøj, P., Toumi, M., Moore, N. D., and Mann, R. D.
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RISPERIDONE , *SCHIZOPHRENIA treatment , *COHORT analysis , *LONGITUDINAL method , *MEDICATION safety , *HEALTH outcome assessment , *HOSPITAL care , *MORTALITY - Abstract
Thomas SHL, Drici MD, Hall GC, Crocq MA, Everitt B, Lader MH, Le Jeunne C, Naber D, Priori S, Sturkenboom M, Thibaut F, Peuskens J, Mittoux A, Tanghøj P, Toumi M, Moore ND, Mann RD. Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP) Objective: To explore whether sertindole increases all-cause mortality or cardiac events requiring hospitalization, compared with risperidone. Method: Multinational randomized, open-label, parallel-group study, with blinded classification of outcomes, in 9858 patients with schizophrenia. Results: After 14147 person-years, there was no effect of treatment on overall mortality (sertindole 64, risperidone 61 deaths, Hazard Ratio (HR) = 1.12 (90% CI: 0.83, 1.50)) or cardiac events requiring hospitalization [sertindole 10, risperidone 6, HR = 1.73 (95% CI: 0.63, 4.78)]: Of these, four were considered arrhythmia-related (three sertindole, one risperidone). Cardiac mortality was higher with sertindole (Independent Safety Committee (ISC): 31 vs. 12, HR=2.84 (95% CI: 1.45, 5.55), P = 0.0022; Investigators 17 vs. 8, HR=2.13 (95% CI: 0.91, 4.98), P = 0.081). There was no significant difference in completed suicide, but fewer sertindole recipients attempted suicide (ISC: 68 vs. 78, HR=0.93 (95% CI: 0.66, 1.29), P = 0.65; Investigators: 43 vs. 65, HR=0.67 (95% CI: 0.45, 0.99), P = 0.044). Conclusion: Sertindole did not increase all-cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole. [ABSTRACT FROM AUTHOR]
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- 2010
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5. Comparison of the Effects of Thioridazine and Mesoridazine on the QT Interval in Healthy Adults After Single Oral Doses.
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Salih, I. S. M., Thanacoody, R. H. K., McKay, G. A., and Thomas, S. H. L.
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CLINICAL medicine ,PLACEBOS ,CHEMICAL ecology ,THIORIDAZINE ,HEART beat - Abstract
We compared the effects of single doses of thioridazine and mesoridazine on the heart rate-corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double-blind, crossover study. Mean maximum increases in the QTc interval following thioridazine (37.3±4.1 ms, P=0.023) and mesoridazine (46.6±7.4 ms, P=0.021) were similar and significantly greater than following placebo (12.9±8.1 ms). The area under the effect–time curve over 8 h following drug administration was similar between the two drugs (129.3±22.1 vs 148.3±43.0 ms h). In conclusion, thioridazine and mesoridazine are associated with similar effects on the QTc interval.Clinical Pharmacology & Therapeutics (2007) 82, 548–554; doi:10.1038/sj.clpt.6100194; published online 4 April 2007 [ABSTRACT FROM AUTHOR]
- Published
- 2007
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6. Factors Affecting Drug Concentrations and QT Interval During Thioridazine Therapy.
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Thanacoody, R. H. K., Daly, A. K., Reilly, J. G., Ferrier, I. N., and Thomas, S. H. L.
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GENETIC polymorphisms ,GENETIC research ,CLINICAL medicine ,CLINICAL pharmacology ,THERAPEUTICS - Abstract
The objective of this study was to investigate factors affecting steady-state plasma concentrations of thioridazine. A cross-sectional study of patients receiving chronic thioridazine was employed. Common allelic variants of CYP2D6 and CYP2C19, as well as thioridazine and metabolite concentrations and QTc intervals, were determined. In 97 patients, dose-corrected plasma concentrations (C/Ds) of thioridazine and metabolites were correlated with age but not sex or CYP2C19 genotype. Patients with no functional CYP2D6 alleles (n=9) had significantly higher C/D for thioridazine (P=0.017) and the ring sulfoxide metabolite and a significantly higher thioridazine/mesoridazine ratio compared with those with 1 functional CYP2D6 allele (n=82). Smokers had significantly lower C/D for thioridazine, mesoridazine, and sulforidazine and significantly lower thioridazine/ring sulfoxide ratios than non-smokers. QTc interval was not significantly affected by CYP2D6 or CYP2C19 genotypes. Plasma concentrations of thioridazine are influenced by age, smoking, and CYP2D6 genotype, but CYP2D6 genotype does not appear to influence on-treatment QTc interval.Clinical Pharmacology & Therapeutics (2007) 82, 555–565; doi:10.1038/sj.clpt.6100195; published online 25 April 2007 [ABSTRACT FROM AUTHOR]
- Published
- 2007
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7. PERSONAL SAVINGS AND TRANSACTIONS BALANCE CHANGES.
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PEARCE, I. F. and THOMAS, S. H.
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- 1986
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8. A pharmacokinetic and pharmacodynamic interaction study between nebivolol and the H2-receptor antagonists cimetidine and ranitidine.
- Author
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Kamali, F., Howes, A., Thomas, S. H. L., Ford, G. A., and Snoeck, E.
- Abstract
Aims The study was designed to investigate the effects of the H
2 -receptor antagonists, cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of nebivolol in healthy volunteers. Methods Twelve healthy volunteers took part in a randomized placebo-controlled cross-over study. Each subject received on three separate occasions placebo, cimetidine (400 mg twice daily) or ranitidine (150 mg twice daily) for 24 h before and 48 h after a single oral dose of nebivolol (5 mg). Nebivolol and its individual (+) and (−) enantiomers were determined tby h.p.l.c. Results Ranitidine had no significant effect on nebivolol pharmacokinetics. Cimetidine, however, resulted in a 21-23% increase in Cmax of unchanged nebivolol and of each enantiomer plus its hydroxylated metabolites. Cimetidine significantly ( P<0.05) increased the AUC [mean±s.d. (95% C.I. of differences in mean)] for unchanged (±)-nebivolol [7.76±3.07 ng ml−1 h with placebo; 11.50±5.40 (1.75, 8.76) ng ml−1 h with cimetidine], (+)-nebivolol plus its hydroxylated metabolites [73.0±18.0 ng ml−1 h with placebo; 91.5±25.7 (1.0, 23.1) ng ml−1 h with cimetidine] and (−)-nebivolol plus its hydroxylated metabolites [101±32 ng ml−1 h with placebo; 123±38 (3.3, 27.0) ng ml−1 h with cimetidine]. Statistical analysis of the resting blood pressure and heart rate and exercise data did not suggest any consistent effects of ranitidine or cimetidine upon the pharmacodynamic effects of nebivolol. Conclusions There was no interaction between ranitidine and nebivolol. Although cimetidine inhibited nebivolol metabolism, it did not have a significant influence on the pharmacodynamics of the drug. [ABSTRACT FROM AUTHOR]- Published
- 1997
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9. THE IMPACT OF SETTLEMENT PROCEDURES ON DAY-OF-THE-WEEK EFFECTS: EVIDENCE FROM THE KUALA LUMPUR STOCK EXCHANGE.
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Clare, A. D., Ibrahim, M. S. B., and Thomas, S. H.
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STOCK exchanges ,STOCKS (Finance) ,PORTFOLIO management (Investments) ,INVESTMENTS - Abstract
This article studies the impact of settlement procedures on day-of-the-week effects, with focus on the Kuala Lumpur Stock Exchange in Malaysia. Extensive evidence exists of anomalies in the behaviour of stock-market returns, particularly for the U.S. market. With the growing international diversification of bond and equity portfolios, particularly in the direction of emerging markets, it is becoming increasingly important for investment managers to understand empirical regularities which may exist in such markets. Some recent and comprehensive studies of the behaviour of emerging market stock return data have focused on the degree of integration of emerging markets with more developed markets and the statistical properties of stock market returns. A number of explanations have been put forward for the weekend effect, including stocks going ex-dividend and the effect of settlement lags. Researchers also looked at the pattern of correlations and cross correlations for lagged and contemporaneous returns, and found that the Far Eastern markets tend to be more strongly correlated with the behaviour of non-Far Eastern markets of previous days than with the behaviour of those non-Far Eastern markets on the same day.
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- 1998
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10. THE EFFECT OF BOND RATING CHANGES AND NEW RATINGS ON UK STOCK RETURNS.
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Barron, M. J., Clare, A. D., and Thomas, S. H.
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CAPITAL market ,BONDS (Finance) ,CREDIT ratings ,MONEY market ,STOCKS (Finance) ,CAPITAL costs - Abstract
This is the first study to use daily data from a major capital market outside of the US to examine the role of corporate bond and commercial paper rating changes on common stock returns. Using data published by Standard and Poors' credit rating agency between 1984 and 1992, we examine the impact of new credit ratings, credit rating changes and CreditWatch announcements on UK common stock returns. We find significant negative excess returns around the date of a downgrade and positive returns close to the date of a positive CreditWatch announcement. Hence, the financial markets would appear to place some importance on rating agency pronouncements in the UK. New ratings, whether short or long-term, have no significant impact on returns. We also attempt to quantify the impact of a new credit rating upon firm cost of capital through measures of conditional volatility and systematic risk. However, we find only weak evidence to suggest that a stock's cost of capital is reduced after a long-term credit rating is awarded for the first time. [ABSTRACT FROM AUTHOR]
- Published
- 1997
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11. Utilization of Appetite Suppressants in England: A Putative Indicator of Poor Prescribing Practice.
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Thomas, S. H. L. and Campbell, M.
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- 1996
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12. Systemic absorption of nebulized morphine compared with oral morphine in healthy subjects.
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MASOOD, A. R. and THOMAS, S. H. L.
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The inhalation of nebulized morphine has been advocated to treat dyspnoea and pain in patients with cancer. We have compared plasma morphine concentrations in healthy volunteers after nebulized (50 mg in 4 ml saline), oral (10 mg solution) and intravenous (5 mg) morphine sulphate. Bioavailability was estimated by dividing the morphine concentration AUC/dose by that obtained after intravenous morphine. Peak plasma morphine concentrations were achieved more rapidly after nebulized than oral morphine, occurring within 10 min in all subjects. The systemic bioavailabilities of morphine (mean ± s.d.) were 5 ± 3% and 24 ± 13% for the nebulized and oral routes respectively. Nebulization is a rapid but inefficient method of administering morphine. It may provide more rapid pain relief compared with oral morphine but clinical studies are needed to confirm this. [ABSTRACT FROM AUTHOR]
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- 1996
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13. Influence of CYP2D6 genotype on the QTc interval and plasma concentrations of thioridazine and its metabolites in psychiatric patients taking chronic therapy.
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Thanacoody, R., Daly, A. K., and Thomas, S. H.
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- 2003
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14. Differences in QTC interval between male and female subjects prescribed the class III antiarrhythmic drug amiodarone.
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Thomas, S. H. and Eraky, H. El
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- 2003
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15. Cardiac safety of noncardiac drugs.
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Thomas, S. H. L.
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HEART diseases , *NONFICTION - Abstract
Reviews the book "Cardiac Safety of Noncardiac Drugs."
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- 2005
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16. Pregnancy outcome following maternal use of zanamivir or oseltamivir during the 2009 influenza A/H1N1 pandemic: a national prospective surveillance study.
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Dunstan HJ, Mill AC, Stephens S, Yates LM, and Thomas SH
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- Adolescent, Adult, Antiviral Agents adverse effects, Epidemiological Monitoring, Female, Humans, Middle Aged, Oseltamivir adverse effects, Pregnancy, Prospective Studies, United Kingdom, Young Adult, Zanamivir adverse effects, Antiviral Agents therapeutic use, Influenza A Virus, H1N1 Subtype, Influenza, Human drug therapy, Influenza, Human epidemiology, Oseltamivir therapeutic use, Pandemics, Pregnancy Complications, Infectious drug therapy, Pregnancy Complications, Infectious epidemiology, Pregnancy Outcome, Zanamivir therapeutic use
- Abstract
Objective: To conduct enhanced surveillance for signals of teratogenesis following use of the neuraminidase inhibitors zanamivir and oseltamivir in the treatment or post-exposure prophylaxis of 2009 A/H1N1 influenza during pregnancy., Design: Prospective cohort study, using national surveillance data collected by the UK Teratology Information Service (UKTIS) during the 2009 A/H1N1 pandemic., Setting: United Kingdom., Population: Pregnant women who were reported to UKTIS by healthcare professionals seeking advice about exposure to zanamivir and oseltamivir or to other non-teratogenic drugs., Methods: Pregnancy outcomes were collected for prospectively reported pregnancies exposed to zanamivir (n = 180) or oseltamivir (n = 27), and compared with a reference group of 575 prospectively reported pregnancies exposed to non-teratogenic drugs over the same period., Main Outcome Measures: Rates of major congenital malformation, preterm delivery and low birth weight., Results: No significant differences in overall rates of major malformation in live-born infants [adjusted odds ratios (aOR): zanamivir 0.37 (95% confidence interval 0.02-2.70); oseltamivir aOR 0.81 (0.05, 14.15)], preterm delivery [aOR: zanamivir 0.95 (0.45, 1.89); oseltamivir aOR 1.68 (0.38, 5.38)] or low birth weight [aOR: zanamivir 0.94 (0.25, 2.90); oseltamivir aOR 4.12 (0.59, 17.99)] were observed following exposure at any gestation. No major malformations were reported in 37 zanamivir or eight oseltamivir first trimester exposures., Conclusion: These surveillance data do not provide a signal that use of zanamivir or oseltamivir in pregnancy is associated with an increased risk of the adverse pregnancy outcomes studied but the data are too limited to state conclusively that there is no increase in risk., (© 2014 Royal College of Obstetricians and Gynaecologists.)
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- 2014
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17. Anti-TNF agents for rheumatoid arthritis.
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Seymour HE, Worsley A, Smith JM, and Thomas SH
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- Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal pharmacology, Antirheumatic Agents adverse effects, Antirheumatic Agents pharmacology, Disability Evaluation, Drug Therapy trends, Etanercept, Humans, Immunoglobulin G adverse effects, Immunoglobulin G pharmacology, Infliximab, Treatment Outcome, Tumor Necrosis Factor-alpha antagonists & inhibitors, Antibodies, Monoclonal therapeutic use, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid drug therapy, Immunoglobulin G therapeutic use, Receptors, Tumor Necrosis Factor therapeutic use, Tumor Necrosis Factor-alpha metabolism
- Published
- 2001
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18. Effectiveness of delayed activated charcoal administration in simulated paracetamol (acetaminophen) overdose.
- Author
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Yeates PJ and Thomas SH
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- Acetaminophen blood, Adult, Analgesics, Non-Narcotic blood, Antidotes administration & dosage, Area Under Curve, Charcoal administration & dosage, Cross-Over Studies, Delayed-Action Preparations, Drug Overdose, Female, Half-Life, Humans, Male, Acetaminophen poisoning, Analgesics, Non-Narcotic poisoning, Antidotes therapeutic use, Charcoal therapeutic use
- Abstract
Aims: Oral activated charcoal is used to treat drug overdose and is effective at reducing drug absorption when administered within 1 h of drug ingestion. There are fewer data on efficacy when the delay is longer, as is the case in most drug overdoses. This study investigated the efficacy of activated charcoal at preventing paracetamol (acetaminophen) absorption after simulated overdose when administration was delayed between 1 and 4 h., Methods: An open randomized-order four-way crossover study was performed in healthy volunteers comparing the effect of activated charcoal 50 g on the absorption of 3 g paracetamol tablets when administered after an interval of 1, 2 or 4 h or not at all. Plasma paracetamol concentrations were measured over 9 h after paracetamol ingestion using h.p.l.c. and areas under the curve between 4 and 9 h (AUC(4,9 h)) calculated as a measure of paracetamol absorption., Results: Activated charcoal significantly reduced paracetamol AUC(4,9 h) when administered after 1 h (mean reduction 56%; 95% Confidence intervals 34, 78; P<0.002) or 2 h (22%; 6, 39; P<0.03) but not after 4 h (8%; -8, 24). When administered after 1 h activated charcoal reduced individual plasma paracetamol concentrations significantly at all times between 4 and 9 h after paracetamol administration. Administration at 2 or 4 h had no significant effect., Conclusions: These results in healthy volunteers cannot be extrapolated directly to poisoned patients. However, they provide no evidence of efficacy for activated charcoal when administered after an interval of more than 2 h.
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- 2000
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19. The use of atypical antipsychotics in the management of schizophrenia.
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Campbell M, Young PI, Bateman DN, Smith JM, and Thomas SH
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- Antipsychotic Agents adverse effects, Antipsychotic Agents economics, Basal Ganglia Diseases chemically induced, Clinical Trials as Topic, Cost-Benefit Analysis, Humans, Mood Disorders drug therapy, Antipsychotic Agents therapeutic use, Schizophrenia drug therapy
- Abstract
Long-term drug treatment of schizophrenia with conventional antipsychotics has limitations: an estimated quarter to one third of patients are treatment-resistant; conventional antipsychotics have only a modest impact upon negative symptoms (poverty of thought, social withdrawal and loss of affect); and adverse effects, particularly extrapyramidal symptoms (EPS). Newer, so-called atypical, antipsychotics such as olanzapine, risperidone, sertindole and clozapine (an old drug which was re-introduced in 1990) are claimed to address these limitations. Atypical agents are, at a minimum, at least as effective as conventional drugs such as haloperidol. They also cause substantially fewer extrapyramidal symptoms. However, some other adverse effects are more common than with conventional drugs. For example, clozapine carries a significant risk of serious blood disorders, for which special monitoring is mandatory; it also causes troublesome drowsiness and increased salivation more often than conventional agents. Some atypical agents cause more weight gain or QT prolongation than older agents. The choice of therapy is, therefore, not straightforward. At present, atypical agents represent an advance for patients with severe or intolerable EPS. Most published evidence exists to support the use of clozapine, which has also been shown to be effective in schizophrenia refractory to conventional agents. However, the need for compliance with blood count monitoring and its sedative properties make careful patient selection important. The extent of any additional direct benefit offered by atypical agents on negative symptoms is not yet clear. The lack of a depot formulation for atypical drugs may pose a significant practical problem. To date, only two double-blind studies in which atypical agents were compared directly have been published. Neither provides compelling evidence for the choice of one agent over another. Atypical agents are many times more expensive than conventional drugs. Although drug treatment constitutes only a small proportion of the costs of managing schizophrenia, the additional annual cost of the use of atypical agents in, say, a quarter of the likely U.K. schizophrenic population would be about 56 M pound sterling. There is only limited evidence of cost-effectiveness. Atypical antipsychotics are not currently licensed for other conditions where conventional antipsychotics are commonly used, such as behaviour disturbance or dementia in the elderly. Their dose, and place in treatment in such cases have yet to be determined.
- Published
- 1999
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20. A pharmacokinetic and pharmacodynamic interaction study between nebivolol and the H2-receptor antagonists cimetidine and ranitidine.
- Author
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Kamali F, Howes A, Thomas SH, Ford GA, and Snoeck E
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- Adult, Area Under Curve, Benzopyrans blood, Benzopyrans pharmacology, Blood Pressure drug effects, Drug Interactions, Ethanolamines blood, Ethanolamines pharmacology, Exercise, Heart Rate drug effects, Humans, Male, Nebivolol, Placebos, Single-Blind Method, Benzopyrans pharmacokinetics, Cimetidine pharmacology, Ethanolamines pharmacokinetics, Histamine H2 Antagonists pharmacology, Ranitidine pharmacology
- Abstract
Aims: The study was designed to investigate the effects of the H2-receptor antagonists, cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of nebivolol in healthy volunteers., Methods: Twelve healthy volunteers took part in a randomized placebo-controlled cross-over study. Each subject received on three separate occasions placebo, cimetidine (400 mg twice daily) or ranitidine (150 mg twice daily) for 24 h before and 48 h after a single oral dose of nebivolol (5 mg). Nebivolol and its individual (+) and (-) enantiomers were determined tby h.p.l.c., Results: Ranitidine had no significant effect on nebivolol pharmacokinetics. Cimetidine, however, resulted in a 21-23% increase in Cmax of unchanged nebivolol and of each enantiomer plus its hydroxylated metabolites. Cimetidine significantly (p < 0.05) increased the AUC [mean +/- s.d. (95% C.I. of differences in mean)] for unchanged (+/-)-nebivolol [7.76 +/- 3.07 ng ml-1 h with placebo; 11.50 +/- 5.40 (1.75, 8.76) ng ml-1 h with cimetidine], (+)-nebivolol plus its hydroxylated metabolites [73.0 +/- 18.0 ng ml-1 h with placebo; 91.5 +/- 25.7 (1.0, 23.1) ng ml-1 h with cimetidine] and (-)-nebivolol plus its hydroxylated metabolites [101 +/- 32 ng ml-1 h with placebo; 123 +/- 38 (3.3, 27.0) ng ml-1 h with cimetidine]. Statistical analysis of the resting blood pressure and heart rate and exercise data did not suggest any consistent effects of ranitidine or cimetidine upon the pharmacodynamic effects of nebivolol., Conclusions: There was no interaction between ranitidine and nebivolol. Although cimetidine inhibited nebivolol metabolism, it did not have a significant influence on the pharmacodynamics of the drug.
- Published
- 1997
- Full Text
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21. Drug-induced QT interval prolongation.
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Thomas SH
- Subjects
- Humans, Arrhythmias, Cardiac chemically induced, Electrocardiography drug effects
- Published
- 1996
22. Effect of oxybutynin on the QTc interval in elderly patients with urinary incontinence.
- Author
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Hussain RM, Hartigan-Go K, Thomas SH, and Ford GA
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- Aged, Aged, 80 and over, Heart Rate drug effects, Humans, Mandelic Acids therapeutic use, Middle Aged, Electrocardiography drug effects, Mandelic Acids pharmacology, Parasympatholytics pharmacology, Urinary Incontinence drug therapy
- Abstract
1. Terodiline, an anticholinergic drug with calcium antagonist properties, is associated with QT prolongation and ventricular arrhythmias. It is not known if oxybutynin, a drug with a similar pharmacological profile, causes QT prolongation. ECGs were obtained before and at least 4 weeks after commencement of oxybutynin (mean daily dose 7.6, range 2.5-10 mg), in 21 elderly (mean age 75, range 58-88 years) patients treated for urinary incontinence. Heart rate, (mean +/- s.d.) 74 +/- 11 vs 69 +/- 11 beats min-1, -6 (-13,2), before vs during oxybutynin therapy, mean difference (95% confidence intervals); PR interval, 168 +/- 27 vs 156 +/- 27 ms, -11 (-26,3); QTc 454 +/- 27 vs 447 +/- 31 ms1/2, -9 (-23,5), and QTc dispersion, QTc max-QTc min, 68 +/- 24 vs 63 +/- 26 ms1/2, -1 (-15,14) were all unaltered by oxybutynin therapy. The lack of an effect on resting heart rate suggests that oxybutynin has little anticholinergic action at cardiac M2 receptors at usually administered doses. Oxybutynin therapy is not associated with QTc interval prolongation and is unlikely to produce ventricular arrhythmias.
- Published
- 1996
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23. Paracetamol elimination in patients with non-insulin dependent diabetes mellitus.
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Kamali F, Thomas SH, and Ferner RE
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- Aged, Female, Humans, Kidney metabolism, Male, Metabolic Clearance Rate, Middle Aged, Acetaminophen pharmacokinetics, Diabetes Mellitus, Type 2 metabolism
- Abstract
The pharmacokinetics and metabolism of an intravenous dose (500 mg) of paracetamol were studied in a group of non-insulin dependent diabetic patients (n = 10) and in a group of healthy control subjects (n = 9). Paracetamol clearance, half-life and the partial clearance to paracetamol glucuronide were not significantly different, but the partial clearance to paracetamol sulphate was significantly reduced (62 +/- 18 vs 86 +/- 17 ml h-1 kg-1 (mean +/- s.d.)) and the renal clearance of paracetamol was significantly increased (56 +/- 20 vs 22 +/- 6 ml h-1 kg-1 (mean +/- s.d.)) in the non-insulin dependent diabetic patients, compared with the control group.
- Published
- 1993
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24. Impedance cardiography using the Sramek-Bernstein method: accuracy and variability at rest and during exercise.
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Thomas SH
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- Adult, Aged, Cardiography, Impedance standards, Coronary Disease diagnosis, Exercise physiology, Humans, Male, Middle Aged, Rest physiology, Stroke Volume, Systole, Cardiography, Impedance methods
- Abstract
1. Sramek and Bernstein's method of impedance cardiography is a simple, non-invasive and inexpensive computerised way of measuring stroke volume and systolic time intervals. In this study measurements made using the method were compared with those found simultaneously using established reference techniques. 2. In healthy volunteers there was no significant bias (d) and narrow 95% limits of agreement (d +/- 2s) when impedance and mechanophonocardiographic measurements of pre-ejection period (PEP, d = 0.3, d + 2s = 7.3, d-2s = -6.6 ms), ventricular ejection time (VET, d = 1.5, d + 2s = 17.7, d-2s = 14.6 ms) and PEP/VET ratio were compared. 3. In critically ill patients there was moderate agreement between impedance and thermodilution measurements of stroke volume (d = 8.1 (P < 0.05), d + 2s = 35.5, d-2s = -19.4 ml) and drug-induced changes in stroke volume were accurately detected. 4. In healthy volunteers agreement between impedance and dye dilution measurements of stroke volume was moderate, and similar at rest and during exercise (d = 3.4, d-2s = -31.1, d + 2s = 37.9 ml), however impedance underestimated exercise-induced increases in stroke volume (P < 0.05). 5. In patients with coronary heart disease impedance measurements correlated with angiographic left ventricular ejection fraction included the PEP/VET ratio (r = -0.81), stroke volume index (r = 0.65) and Heather index (r = 0.58, all P < 0.001), however the PEP/VET ratio could not be used to estimate the left ventricular ejection fraction with sufficient accuracy. 6. This impedance method provides reproducible semi-quantitative measurements of cardiac performance and blood flow. Its use for making pharmacodynamic measurements can be justified when invasive methods are considered inappropriate.
- Published
- 1992
25. A comparison of the cardiovascular effects of phenylpropanolamine and phenylephrine containing proprietary cold remedies.
- Author
-
Thomas SH, Clark KL, Allen R, and Smith SE
- Subjects
- Administration, Oral, Adult, Caffeine pharmacology, Cardiography, Impedance, Double-Blind Method, Female, Humans, Male, Random Allocation, Hemodynamics drug effects, Nasal Decongestants pharmacology, Phenylephrine pharmacology, Phenylpropanolamine pharmacology
- Abstract
1. The cardiovascular effects of the proprietary cold remedies, Mu-cron and Boots Cold Relief tablets were compared with 'placebo' Boots Pain Relief tablets in a double-blind study involving 16 healthy volunteers. Measurements (impedance cardiography, forearm plethysmography) were made over 4 h after oral drug administration. 2. Two Mu-cron tablets (containing phenylpropanolamine [(1R,2S)- plus (1S,2R)-norephedrine] 50 mg) increased blood pressure (maximal effect 18 +/- 1/8 +/- 1 mm Hg (mean +/- s.e. mean), P less than 0.001), stroke volume (4.9 +/- 0.8 ml m-2, P less than 0.05), total peripheral resistance (243 +/- 27 dyn s cm-5 m2, P less than 0.001) and forearm vascular resistance (1.3 +/- 0.3 mm Hg ml-1 min, P less than 0.01) and reduced the ratio of pre-ejection period to ventricular ejection time (-0.031 +/- 0.003, P less than 0.05) and forearm blood flow (-2.6 +/- 0.5 ml min-1, P less than 0.05) but did not affect heart rate or cardiac index. 3. Two Boots Cold Relief tablets (containing phenylephrine 10 mg and caffeine 60 mg) caused a small and short-lived increase in total peripheral resistance but did not have consistent effects on other measurements. Two Boots Pain Relief tablets (containing caffeine 60 mg) did not have important cardiovascular effects. 4. The cardiovascular effects of phenylpropanolamine, including vasoconstriction and an increase in cardiac performance, are consistent with its alpha- and beta 1-adrenoceptor agonist action. While it may help the symptoms of rhinitis, its use in patients with heart disease or hypertension is hazardous.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1991
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