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L Frith

Publications and source records attributed to L Frith.

11 recordsLinked to original sources
PubMed2001

Gamete donation and anonymity: the ethical and legal debate.

The British government is currently considering whether to review the law on information provision for donor offspring. This paper therefore provides an overview of the current international legal situation relating to donor anonymity and a review of the key arguments and evidence on both sides of the debate. While the British government is considering all aspects of information giving, both identifying and non-identifying donor information, this paper will focus on the most contentious issue: the provision of information that would identify the donor. The current legal situation in the UK and internationally is examined, drawing attention to a possible international trend towards more information giving. The evolution of the present British system is outlined and it is asked whether some of the concerns and values that gave rise to the practice of anonymous donation are still relevant today. Looking at the concept of a child's right to know their biological identity it examines the possible basis of such a right and its potential conflict with the perceived interests of the child's parents. Finally, some of the practical obstacles to non-anonymous donation are evaluated. The paper concludes that a review of the British law is both timely and desirable.

Confidentiality↗
PubMed2000

Ignorance is bliss? HIV and moral duties and legal duties to forewarn.

In 1997, a court in Cyprus jailed Pavlos Georgiou for fifteen months for knowingly infecting a British woman, Janet Pink, with HIV-1 through unprotected sexual intercourse. Pink met Georgiou in January 1994 whilst on holiday. She discovered that she had contracted the virus from him in October 1994 but continued the relationship until July 1996 when she developed AIDS. She returned to the UK for treatment and reported Georgiou to the Cypriot authorities. There have been a number of legal cases involving deliberate transmission of HIV, but most have involved forced exposure to infected bodily fluids for example, rape or biting, and have been dealt with using the existing legislation for rape or assault. While it is often difficult to prove responsibility for transmission in cases of forced exposure to HIV, it is even more contentious in cases like those of Janet Pink where an individual has consented to sex but claims that he/she was not forewarned of his/her partner's HIV-positive status. At present there is no specific criminal offence of having unprotected sexual intercourse without disclosing one's HIV-positive status but a prosecution could possibly be brought under any one of a number of existing offences. Perhaps a change of policy needs to be considered. The Home Office has issued a consultation document which outlines a proposal that will allow the criminalization of intentional transmission of diseases, like HIV, that are likely to cause serious harm. This revised legislation would cover all other potentially fatal diseases (including salmonella and legionnaire's disease, for instance) but seems primarily to be targeted at HIV transmission. Should transmission of HIV through consensual sex, without the HIV-positive status of the individual being disclosed, be an offence? This question, and that of whether there is a moral obligation to disclose a positive HIV status prior to having a sexual relationship is the subject of this paper.

Crime↗
PubMed1999

Troglitazone in combination with sulphonylurea improves glycaemic control in Type 2 diabetic patients inadequately controlled by sulphonylurea therapy alone. Troglitazone Study Group.

AIM: The aim of this study was to investigate the effectiveness of troglitazone (a peroxisome proliferator-activated receptor-gamma agonist developed primarily for the treatment of Type 2 diabetes mellitus (DM)), 100 or 200mg/day, in terms of glycaemic control, lipid profile and tolerability, when given in addition to existing sulphonylurea therapy. METHODS: A 16-week, randomized, parallel-group placebo-controlled trial in 259 Type 2 diabetic patients already on sulphonylurea therapy. RESULTS: At week 16, adjusted geometric mean HbA1c with troglitazone 100mg (7.7%; P=0.023) and 200mg (7.4%; P<0.001) was lower with sulphonylurea alone (8.2%). At all weeks, adjusted geometric mean fasting serum glucose levels were lower in both troglitazone groups, compared with sulphonylurea alone (P=0.007 to P<0.001). At week 16, both troglitazone groups showed reductions in immune reactive insulin compared with sulphonylurea alone (200mg, 13%; P=0.032: 100mg, 5%; NS). Troglitazone reduced serum levels of nonesterified fatty acids at week 16 (100 g, 12%; P=0.042) and at all weeks (200mg, 17-24%; P=0.014 to P<0.001). The incidence of drug-related adverse events was similar in all groups (23-24% of patients). There was no apparent association between hypoglycaemia and the addition of troglitazone to sulphonylurea therapy. CONCLUSIONS: Troglitazone 100 or 200 mg added to usual sulphonylurea therapy in patients with Type 2 DM is associated with a significant improvement in glycaemic control, without altering the adverse-event profile of the sulphonylurea.

Blood Glucose↗
PubMed1998

Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group.

BACKGROUND: The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial because of a lack of placebo-controlled studies. We compared the effect of inhaled fluticasone propionate with placebo in the treatment of patients with COPD. METHODS: We used a randomised, double-blind, placebo-controlled design. We enrolled from 13 European countries, New Zealand, and South Africa, 281 outpatient current or ex-smokers, aged between 50 and 75 years. They had a forced expiratory volume in 1 s (FEV1) of between 35% and 90% of predicted normal values, a ratio of FEV1 to forced vital capacity of 70% or less and bronchodilator reversibility of less than 15%, as well as a history of chronic bronchitis. Patients were randomly assigned fluticasone propionate 500 microg (n=142) or placebo (n=139) twice daily via a metered-dose inhaler for 6 months. The main outcome measures were the number of patients who had at least one exacerbation by the end of treatment, the number and severity of exacerbations, clinic lung function, diary card symptoms and peak expiratory flow and 6 min walking distance. FINDINGS: 51 (37%) patients in the placebo group compared with 45 (32%) in the fluticasone propionate group had had at least one exacerbation by the end of treatment (p=0.449). Significantly more patients had moderate or severe exacerbations in the placebo group than in the fluticasone propionate group (86% vs 60%, p<0.001). Diary-card and clinic morning peak expiratory flows improved significantly in the fluticasone propionate group (p<0.001, p=0.048, respectively), as did clinic FEV1 (p<0.001), forced vital capacity (p<0.001), and mid-expiratory flow (p=0.01). Symptom scores for median daily cough and sputum volume were significantly lower with fluticasone propionate treatment than with placebo (p=0.004 and p=0.016, respectively). At the end of treatment, patients on fluticasone propionate had increased their 6 min walking distance significantly more than those on placebo (p=0.032). Fluticasone propionate was tolerated as well as placebo, with few adverse effects and without a clinically important effect on mean serum cortisol concentration. INTERPRETATION: Fluticasone propionate may be of clinical benefit in patients with COPD over at least 6 months. Inhaled corticosteroids may have an important role in the long-term treatment of COPD.

Administration, Inhalation↗
PubMed1997

Implications of socio-cultural contexts for the ethics of clinical trials.

BACKGROUND: Health technology assesment (HTA) requires scientifically rigorous experimentation involving patients as subjects. HTA itself is required so that treatment given to patients will be both effective and efficient; this requirement is itself ethical in nature. At the same time it is essential that the methods used in HTA are ethically sound. Most healthcare researchers agree that the most effective and soundest method for assessing treatments is the randomised controlled trial (RCT). However, some researchers believe that the RCT is unethical, either in essence, or for use in some forms of medical research and HTA. Furthermore, many patients seem unable to understand the principles and purposes of the RCT, a factor which is highly detrimental for the validity of informed consent. Informed consent is the key to the ethics of medical research, both in most theories and in all codes of research conduct. Many RCTs therefore risk being unethical in practice, even if ethical in principle. AIM OF REPORT: To survey the main objections to the RCT and its alternatives. To assess the philosophical and methodological basis of these objections, and of the methods recommended for addressing them. To identify areas where objections are founded in social or cultural factors normally overlooked in ethical argument about the RCT methodology. To identify alternative arguments or methods which might resolve ethical conflicts in this area. HOW THE RESEARCH WAS CONDUCTED: The methods used were adapted from systematic reviews in medicine. Systematic searches of Medline, Psychlit and Sociofile CD-ROM databases; hand-searches of the major journals in general medicine and surgery, medical ethics and philosophy; and searches of books were carried out. The literature survey was restricted to articles published or abstracted in English. A database of the most relevant and useful materials was compiled, and is accessible on the Internet (http://www.liv.ac.uk/sdthomps/page1.html). RESEARCH FINDINGS: UNDERSTANDING RCTS AND THEIR ALTERNATIVES: There is some evidence of difficulty in understanding the aims and methods of RCTs, and some disquiet about elements of the RCT methodologies. These objections are well known and much discussed, and concern the use of placebo, the continuation of trials after significant differentials in benefit or harm are apparent, and randomisation. CULTURAL OR RELIGIOUS OBJECTIONS: There was an absence of evidence of cultural or religious objections to randomisation, placebo or other kinds of controlled prospective trials. This most likely reflects an absence of research rather than absence of objections. (ABSTRACT TRUNCATED)

Cultural Diversity↗
PubMed1972

The effects of amino acids on albumin synthesis by the isolated perfused rat liver.

Albumin synthesis was measured in the isolated perfused rat liver by using the livers of both well-fed and starved rats. Starvation markedly decreased albumin synthesis. The livers from starved rats were unable to increase synthesis rates after the addition to the perfusates of single amino acids or the addition of both glucagon and tryptophan. Arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine, added together to ten times their normal peripheral blood concentrations, restored synthesis rates to normal. The plasma aminogram (i.e. the relative concentrations, of amino acids) was altered by depriving rats of protein for 48h. The use of blood from the deprived rats as perfusate, instead of normal blood, decreased albumin synthesis rates significantly by livers obtained from well-fed rats. The addition of single amino acids, including the non-metabolizable amino acid, alpha-aminoisobutyric acid, to the above mixture increased albumin synthesis rates to normal values. It is concluded that amino acids play an important role in the control of albumin synthesis and that more than one mechanism is probably involved.

Albumins↗
PubMedDate not supplied

Practical issues in equivalence trials.

Equivalence trials aim to show that two treatments have equivalent therapeutic effects. The approach is to define, in advance, a range of equivalence -d to +d for the treatment difference such that any value in the range is clinically unimportant. If the confidence interval for the difference, calculated after the trial, lies entirely within the interval, then equivalence is claimed. Glaxo Wellcome has carried out a series of trials using this methodology to assess new formulations of inhaled beta-agonists and inhaled steroids in asthma. Eleven of these trials are used to review some practical issues in equivalence trials. For the series of asthma trials, a range for peak expiratory flow rate (PEF) from -15 to +15 l/min was chosen to be the range of equivalence. This fitted well with physicians' opinions and with previously demonstrated differences between active and placebo. The choice of the size of the confidence interval should depend on the medical severity of the clinical endpoints under consideration and the level of risk acceptable in assuming equivalence if a difference of potential importance exists. From this point of view, a recommendation in the CPMP Note for Guidance on Biostatistics that 95 per cent confidence intervals should be used is inappropriate. Intent-to-treat (ITT) and per-protocol (PP) analyses were compared for the eleven asthma trials. Confidence intervals were always wider for the PP analysis and this was entirely due to the smaller number of subjects included in the PP analysis. There was no evidence that the ITT analyses were more conservative in their estimates of treatment difference. The need to demonstrate equivalence in both an ITT and a PP analysis in a regulatory trial increases the regulatory burden on drug developers. The relative importance of the two analyses will depend on the definitions used in particular therapeutic areas. Demonstrating equivalence in one population with strong support from the other would be preferred from the Industry viewpoint. In trials with regulatory importance, prior agreement with regulators on the role of ITT and PP populations should be sought. Trial designs will need to take account of the estimated size of the PP population if adequate power is needed for both analyses. Careful design in the series of asthma trials, particularly identifying a population of patients with potential to improve, resulted in notable increases in lung function during the course of the trials for both treatments. This provided reassurance that equivalence was not due to a lack of efficacy for both treatments. In one trial equivalence was demonstrated overall but a treatment by country interaction was noted. However, this interaction could not be attributed to differences in patient characteristics or baseline data between the countries. Study conduct was also similar in the different countries. The conclusion was that the interaction was spurious and that the trial provided good evidence of equivalence.

Adult↗