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Biomedical subjects

J Chick

Publications and source records attributed to J Chick.

At least 19 recordsLinked to original sources
PubMed2006

Multicentre phase II pharmacokinetic and pharmacodynamic study of OSI-7904L in previously untreated patients with advanced gastric or gastroesophageal junction adenocarcinoma.

A two-stage Simon design was used to evaluate the response rate of OSI-7904L, a liposome encapsulated thymidylate synthase inhibitor, in advanced gastric and/or gastroesophageal adenocarcinoma (A-G/GEJA), administered intravenously at 12 mg m(-2) over 30 min every 21 days. Fifty patients were treated. Median age was 64 years (range 35-82), 62% were male and 89% had ECOG PS of 0/1. A total of 252 cycles were administered; median of 4 per patient (range 1-21). Twelve patients required dose reductions, mainly for skin toxicity. Investigator assessed response rate was 17.4% (95% CI 7.8-31.4) with one complete and seven partial responses in 46 evaluable patients. Twenty-one patients (42%) had stable disease. Median time to progression and survival were 12.4 and 36.9 weeks, respectively. NCI CTCAE Grade 3/4 neutropenia (14%) and thrombocytopenia (4%) were uncommon. The main G3/4 nonhaematological toxicities were skin-related 22%, stomatitis 14%, fatigue/lethargy 10%, and diarrhea 8%. Pharmacokinetic data showed high interpatient variability. Patients with higher AUC were more likely to experience G3/4 toxicity during cycle 1 while baseline homocysteine did not predict toxicity. Response did not correlate with AUC. Elevations in 2'-dU were observed indicating target inhibition. Analysis of TS genotype, TS protein and expression did not reveal any correlation with outcome. OSI-7904L has activity in A-G/GEJA similar to other active agents and an acceptable safety profile.

Adenocarcinoma↗
PubMed2004

Are selective serotonin re-uptake inhibitors associated with an increased risk of self-harm by antidepressant overdose?

OBJECTIVE: To investigate likelihood of self-harm by overdose with antidepressant drugs of different types by examining hospital admission data and poisons inquiries and relating them to prescribing. DESIGN: Retrospective analysis of prospectively collected data on overdose admissions, poisons inquiries and prescribing of antidepressants in Edinburgh and Scotland. SETTING: Poisons treatment unit of the Royal Infirmary of Edinburgh and its surrounding catchment for overdose cases and Scotland for poisons inquiries. PARTICIPANTS: All patients admitted to the Royal Infirmary of Edinburgh between 1 January 2000 and 31 December 2002 with an overdose involving an antidepressant. MAIN OUTCOME MEASURES: Overdose admissions (patients) in relation to prescribing in Edinburgh and poisons inquiries in relation to prescription rates in Scotland. RESULTS: There were 1656 admissions involving 1343 patients. The likelihood of admission for an individual patient in relation to volume of prescribing (likelihood ratio: 95%CI) in the catchment was somewhat smaller for amitriptyline (0.83:0.74-0.92) and sertraline (0.79:0.63-0.99), and somewhat greater for mirtazapine (1.99:1.57-2.51), trazadone (1.30:1.09-1.54) and venlafaxine (0.97:1.81-1.16) [corrected] For poisons inquiries in Scotland, the excess for venlafaxine and mirtazapine was confirmed and likelihood of an inquiry lowest for selective serotonin re-uptake inhibitors (SSRIs). CONCLUSIONS: There was no evidence of an excess likelihood of presentation with overdose with SSRIs, and the likelihood was reduced with sertraline. There was a small excess of both admissions and poisons inquiries for mirtazapine and venlafaxine. This is a concern in view of the increased toxicity of venlafaxine in overdose in comparison with SSRIs.

Adult↗
PubMed1999

Pyoderma gangrenosum with secondary pyarthrosis following propylthiouracil.

The association of pyoderma gangrenosum and arthritic symptoms is well documented. We present a rarely reported variant of this in a 44-year-old woman with pyoderma gangrenosum and bilateral large purulent effusions of her knees. She had no evidence of underlying rheumatoid arthritis or a specific seronegative spondyloarthropathy. Of note she had a history of Graves' disease for which she had been treated with propylthiouracil for 3 years and on investigation at this presentation had a markedly elevated perinuclear antineutrophil cytoplasm antibody (P-ANCA) level with specificities for IgM myeloperoxidase, IgG elastase and IgG lactoferrin. We believe this patient had pyoderma gangrenosum with secondary sterile pyarthrosis and a P-ANCA precipitated by propylthiouracil.

Adult↗
PubMed1999

Ritanserin in relapse prevention in abstinent alcoholics: results from a placebo-controlled double-blind international multicenter trial. Ritanserin in Alcoholism Work Group.

Ritanserin, a long-acting specific 5-HT2 receptor antagonist, revealed promising effects on alcohol intake behavior in both animal and preliminary human studies. To test its effectiveness in alcohol dependence this phase III clinical trial was initiated. In a placebo-controlled, randomized, double-blind international multicenter study 493 patients with moderate or severe alcohol dependence (DSM-III-R) were treated with three doses of ritanserin 2.5 mg/day (n = 122), 5 mg/day (n = 123), 10 mg/day (n = 126), or placebo (n = 122) over a period of 6 months. Ritanserin was well tolerated. The most frequent adverse experiences were headache and insomnia. A small increase in weight in the ritanserin-treated patients was observed. There were no significant differences between any dose of ritanserin and placebo in the relapse-rate, the time to relapse, craving for alcohol, or quantity and frequency of drinking after relapse. So far, neither ritanserin nor any other serotonergic medication has shown its specific effectiveness in relapse prevention in alcohol dependence.

Adult↗
PubMed1999

Can light or moderate drinking benefit mental health?

Observational studies in several cultures show light and moderate drinking to be associated with better emotional and social adjustment than abstinence. However, adjustments for pre-existing personality characteristics and socialisation need to be made, and abstainers who are ex-drinkers must be excluded. There is still insufficient evidence to suggest that emotional health can be improved by light or moderate drinking. For cognition, consumption of up to 65 g/day is not associated with chronic inefficiencies. With regard to cognitive decline in older people, emerging evidence suggests the possibility that such decline may be reduced by light drinking. The elderly in institutions probably benefit from a 'social hour' when alcoholic beverage is available. Doctors considering giving advice to drink to improve health should be very cautious and note a number of caveats.

Adolescent↗
PubMed1999

Limitations of CDT and GGT in detecting relapses in patients attending an alcohol problems clinic.

Biochemical markers of alcohol consumption are useful for the detection and monitoring of problem drinking. Blood samples from 37 patients attending an alcohol treatment clinic were analysed for GGT and %CDT, and results were compared with self-reported periods of abstinence and alcohol consumption. Poor correlation was obtained between GGT and %CDT, and between these assays and self-reported alcohol use. The apparent sensitivity and specificity of GGT (57%, 63%) and %CDT (43%, 88%), were considerably lower than those reported by other workers.

Alcohol Drinking↗
PubMed1999

Safety issues concerning the use of disulfiram in treating alcohol dependence.

Disulfiram is known to cause hepatitis, which is sometimes fatal. The best estimate of the frequency of disulfiram-induced fatal hepatitis is 1 case in 30,000 patients treated/year. Its appears to be more common in patients given disulfiram for the treatment of nickel sensitivity. Frequent blood testing for liver function is probably not necessary, but patients taking disulfiram should be in regular contact with a physician. There are rare reports of psychosis and confusional states in conjunction with disulfiram treatment and peripheral neuropathy and optic neuritis have been reported; these effects are dose-related. Psychiatric complications appear to be more common with the use of disulfiram in India than in Western countries. Of the less serious adverse effects, tiredness, headache and sleepiness are the most common. Deaths from the disulfiram-alcohol (ethanol) interaction have not been reported in recent years, possibly because the dosages used are lower than those used 40 years ago, and patients with cardiac disease are now excluded from treatment. There is no evidence to suggest that disulfiram causes cancer. Of note, there are drug interactions with compounds that utilise the cytochrome P450 enzyme system. Disulfiram can be viewed as a drug with a moderate record of adverse effects. Alcohol dependence, for which it can be a helpful treatment, is associated with a high morbidity and mortality.

Alcohol Deterrents↗
PubMed1997

Carbohydrate deficient transferrin in detecting relapse in alcohol dependence.

Patients reports together with findings at clinical examination and information from an informant such as a relative were used to categorise patients as relapsed or not relapsed during a 6 month period of out-patient treatment at an alcohol problems clinic. At each fortnightly visit, blood was taken for measurement of serum gamma-glutamyl transferase and carbohydrate deficient transferrin (Pharmacia method). A total of 53 patients attended for at least one follow-up visit. Mean CDT differentiated relapsers from non-relapsers at seven of the 11 visits (P < 0.05), but at no visit did mean GGT differentiate. CDT tended to become elevated after a relapse more quickly than GGT. However, whether using upper limit of normal (ULN), or defining a 'positive test' as > last test and either > 20% above lowest previous test or > ULN, specificity (averaged over the 11 visits) was greater for GGT than CDT. Some of the false positive results for CDT were in patients who, shortly after having a positive test, relapsed, suggesting that a rising CDT can herald a relapse admitted by the patient. This could not be shown for false positive GGT results. Inspection of individual trajectories of alcohol consumption and blood test results shows that for some patients GGT is the more effective marker of relapse, whilst for others CDT operates better.

Adult↗
PubMed1997

Evidence suggesting increasing health damage in Scotland related to alcohol.

General hospitals in Scotland have experienced a steep rise in discharge rates for alcohol-related diagnoses. This cannot fully be explained by changes in drinking in the general population, a cohort of heavy drinkers, changes in diagnostic practice, or the closure of beds in psychiatric hospitals. Moreover, there has been an increase in deaths from alcoholic liver disease, not easily explained by change in diagnostic practice or a putative cohort of polysubstance abusers with viral hepatitis. Changes in society such as greater income disparity and greater social isolation may contribute and have not been off-set by improvements in availability or outcome of treatment.

Adolescent↗
PubMed1996

The SECCAT survey: I. The costs and consequences of alcoholism.

The SECCAT survey assessed the Socio-Economic Costs and Consequences of Alcoholism Treatment. Basic demographic and health service resource use data (for a previous 6-month period) were obtained fro a cohort of 586 eligible patients who had had treatment at the Alcohol Problems Clinic (APC) in Edinburgh. The cohort was 75% male with a mean age of 46.0 years. Seventy-six per cent had an initial diagnosis of alcohol dependence and 21% alcohol abuse. Use of health services was highly variable. Thirty-six per cent agreed to be interviewed to provide data on their level of abstinence, on resource use, on quality of life (SF-36), on socio-economic characteristics and key adverse events. These 212 individuals had similar age and sex ratios to the full cohort, but alcohol abusers were under-represented. Nineteen patients reported no days of abstinence and 41 were abstinent over the whole 6-month period. Patients experienced a much poorer quality of life than a normal population in terms of all dimensions of the SF-36. The average total health care costs of the interviewed patients were 1134 pounds of which 38% were related to treatment at the APC. Analysis suggests that alcohol-dependent patients make substantially more costly use of resources than abusers and experience a much poorer quality of life. No clear relationship of cost to degree of abstinence has been found. There is a clear and consistent relationship of SF-36 scores and drinking behavior.

Adult↗
PubMed1996

Conference summary: Consensus Conference on Alcohol Dependence and the Role of Pharmacotherapy in its Treatment.

Alcoholism, a major public health problem throughout the world, causes enormous damage to health and quality of life and undermines the well-being of families and society. It is associated with liver disease, cancer, cardiovascular problems, accidental deaths, suicides, and homicides. Because of the internationally recognized severity of this disease, this consensus conference was convened to bring together leading international experts to share ideas with regard to current research in the areas of alcohol dependency and treatment, and to discuss the future directions for the pharmacotherapy of alcoholism. The work presented at this conference points to a substantial evolution in the ability of researchers to understand the mechanism by which alcohol acts on the brain and reinforces the concept that alcoholism is a disease of brain chemistry, with a hereditary predisposition that is triggered by psychological and/or environmental factors that are thus far unidentified. The consensus statements proposed by the participants at the close of the conference highlight the definition, etiology, and prevention of alcoholism, as well as current and potential treatments and recommendations that can be used to guide future pharmacologic research.

Alcohol Deterrents↗
PubMed1995

Acamprosate as an aid in the treatment of alcoholism.

Acamprostate is a gamma-aminobutyric acid (GABA) analogue for which evidence is accumulating of a clinically useful benefit when used as an adjunct for conventional treatments to prevent relapse in alcohol dependence. This paper reviews published randomized controlled studies involving 1304 patients. To date no abstinence syndrome associated with acamprostate has been identified nor serious adverse effects. It is not effective in all patients, and the characteristics of the individuals most likely to respond and the treatment setting and modalities in which it is likely to be most helpful, have yet to be specified.

Acamprosate↗
PubMed1994

Alcohol problems in the general hospital.

The likelihood of a man being admitted to a general hospital for liver disease, myocardial infarction, other cardiovascular disease, upper gastrointestinal disease and acute trauma increases progressively as admitted alcohol intake increases, commencing at an admitted consumption of 30/g per day. Heavy drinkers are also more likely than light drinkers to be admitted for respiratory disorders, presumably because of the connection with smoking. In addition to these and other medical conditions linked to alcohol use, there are admissions directly related to alcohol dependence and its complications such as fits, or delirium. Trends in general hospital discharges for alcohol dependence, psychosis and misuse for the 1980's have been examined in Scotland and found to have increased, in a period when discharges for alcohol disorders from psychiatric hospitals have decreased (Figs 1-3). Changes in diagnostic practices are unlikely to account for such a large change, but a shift from psychiatric to general hospital may have contributed.

Alcohol Drinking↗
PubMed1994

Trends in alcoholism among male doctors in Scotland.

Alcohol abuse within the medical profession has long been an issue of concern. Recently, the General Medical Council reported that half of the doctors reported for health difficulties liable to affect professional competence were found to have an alcohol problem. This paper examines how rates of alcoholism among male doctors in Scotland have changed over the last three decades. Admission and discharge rates for doctors to psychiatric inpatient beds with diagnoses of alcoholism are compared with non-medical professions, for the years 1963-87. The results, assessed in the light of changing Standardized Mortality Rates for liver cirrhosis for the medical profession, suggest that doctors as a group remain at a higher risk of alcoholism compared to other professionals, but that this increased risk appears to be largely accounted for by a cohort of heavy-drinking doctors over the age of 45 years.

Adult↗