Lucy Frith

Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease

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.

HIV self-testing: a time to revise current policy

is now outdated. New technologies that enable rapid and accurate HIV testing are now becoming available. 4 To increase the uptake of HIV testing and truly respect patient autonomy we need to challenge this outmoded practice and remove the legal obstacles to selftesting for HIV. On Nov 3, 2005, the US Food and Drug Administration’s (FDA) blood products advisory committee met to debate the issues raised by a self-test for HIV based on oral fl uids, after its manufacturers declared their intention to seek over-the-counter status. 5 The committee’s meeting is the fi rst stage in a long approval process, but it suggests that self-testing for HIV is being considered in the USA. Most of the experts who spoke at the meeting argued that the

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.1 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/herpartners HIV-positive status. At present there is no specific criminal offence of having unprotected sexual intercourse without disclosing ones HIV-positive status but a prosecution could possibly be brought under any one of a number of existing offences.2 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 criminalisation 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 legionnaires 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.

Beneath the Rhetoric: The Role of Rights in the Practice of Non-Anonymous Gamete Donation

The use of rights based arguments to justify claims that donor offspring should have access to information identifying their gamete donor has become increasingly widespread. In this paper, I do not intend to revisit the debate about the validity of such rights. Rather, the purpose is to examine the way such alleged rights have been implemented by those legislatures that have allowed access to identifying information. I will argue that serious inconsistencies exist between the claim that donor offspring have a right to know the identity of their gamete donor and the way such a right is currently met in practice. I hope to show that in systems where non-anonymous donation is practised, an understanding of the proclaimed right of donor offspring to know their genetic identity is one composed of two different rights--the right to know the circumstances of their conception and the right to information identifying the gamete donor--can provide important insights into this important area of public policy.

Doing challenging research studies in a patient-centred way: a qualitative study to inform a randomised controlled trial in the paediatric emergency care setting

Objective To inform the design of a randomised controlled trial (called EcLiPSE) to improve the treatment of children with convulsive status epilepticus (CSE). EcLiPSE requires the use of a controversial deferred consent process. Design Qualitative interview and focus group study. Setting 8 UK support groups for parents of children who have chronic or acute health conditions and experience of paediatric emergency care. Participants 17 parents, of whom 11 participated in telephone interviews (10 mothers, 1 father) and 6 in a focus group (5 mothers, 1 father). 6 parents (35%) were bereaved and 7 (41%) had children who had experienced seizures, including CSE. Results Most parents had not heard of deferred consent, yet they supported its use to enable the progress of emergency care research providing a childs safety was not compromised by the research. Parents were reassured by tailored explanation, which focused their attention on aspects of EcLiPSE that addressed their priorities and concerns. These aspects included the safety of the interventions under investigation and how both EcLiPSE interventions are used in routine clinical practice. Parents made recommendations about the appropriate timing of a recruitment discussion, the need to individualise approaches to recruiting bereaved parents and the use of clear written information. Conclusions Our study provided information to help ensure that a challenging trial was patient centred in its design. We will use our findings to help EcLiPSE practitioners to: discuss potentially threatening trial safety information with parents, use open-ended questions and prompts to identify their priorities and concerns and clarify related aspects of written trial information to assist understanding and decision-making.

The Role of Birth Certificates in Relation to Access to Biographical and Genetic History in Donor Conception

In 1984, among its recommendations for the regulation of assisted conception services in the UK, the Warnock Committee proposed that the birth certificate of a donor-conceived person should record the fact of donor conception. While this proposal was never implemented, over twenty years later, a Joint Committee of the House of Lords and House of Commons recommended the use of birth certificates as a means of enabling donor-conceived persons to learn the nature of their conception. In response, the Government has committed to review the role of birth certificates. This paper represents an initial contribution to this exercise. It provides an overview of the legislative, policy and practice context of disclosure of donor conception, outlines arguments against and in favour of potential changes to birth certificates, and describes and critiques current propositions for revising birth certification. The paper concludes that there is a case for revising birth certificates and outlines a workable model to promote disclosure without compromising privacy concerns.

Expectations and experiences of gamete donors and donor-conceived adults searching for genetic relatives using DNA linking through a voluntary register

STUDY QUESTION What are the experiences of donor-conceived adults and donors who are searching for a genetic link through the use of a DNA-based voluntary register service? SUMMARY ANSWER Donor-conceived adults and donors held positive beliefs about their search and although some concerns in relation to finding a genetically linked relative were reported, these were not a barrier to searching. WHAT IS KNOWN ALREADY Research with donor-conceived people has consistently identified their interest in learning about-and in some cases making contact with-their donor and other genetic relatives. However, donor-conceived individuals or donors rarely have the opportunity to act on these desires. STUDY DESIGN, SIZE, AND DURATION A questionnaire was administered for online completion using Bristol Online Surveys. The survey was live for 3 months and responses were collected anonymously. PARTICIPANTS/MATERIALS, SETTING, AND METHODS The survey was completed by 65 donor-conceived adults, 21 sperm donors and 5 oocyte donors who had registered with a DNA-based voluntary contact register in the UK. The questionnaire included socio-demographic questions, questions specifically developed for the purposes of this study and the standardized Aspects of Identity Questionnaire (AIQ). MAIN RESULTS AND THE ROLE OF CHANCE Motivations for searching for genetic relatives were varied, with the most common reasons being curiosity and passing on information. Overall, participants who were already linked and those awaiting a link were positive about being linked and valued access to a DNA-based register. Collective identity (reflecting self-defining feelings of continuity and uniqueness), as assessed by the AIQ, was significantly lower for donor-conceived adults when compared with the donor groups (P < 0.05), but not significantly different between linked/not linked or length of time since disclosure of donor conception (all Ps > 0.05) for donor-conceived adults. LIMITATIONS, REASONS FOR CAUTION Participants were members of a UK DNA-based registry which is unique. It was therefore not possible to determine how representative participants were of those who did not register for the service, those in other countries or of those who do not seek information exchange or contact. WIDER IMPLICATIONS OF THE FINDINGS This is the first survey exploring the experiences of donor-conceived adults and donors using a DNA-based voluntary register to seek information about and contact with genetic relatives and the first to measure aspects of identity using standardized measures. Findings provide valuable information about patterns of expectations and experiences of searching through DNA linking, identity and of having contact in the context of donor conception that will inform future research, practice and policy development. STUDY FUNDING/COMPETING INTERESTS No funding was obtained for this study. The authors have no competing interests to declare except for M.C. who was national adviser to UKDL from 2003-2013. TRIAL REGISTRATION NUMBER Not applicable.

How parents and practitioners experience research without prior consent (deferred consent) for emergency research involving children with life threatening conditions: a mixed method study.

Objective Alternatives to prospective informed consent to enable children with life-threatening conditions to be entered into trials of emergency treatments are needed. Across Europe, a process called deferred consent has been developed as an alternative. Little is known about the views and experiences of those with first-hand experience of this controversial consent process. To inform how consent is sought for future paediatric critical care trials, we explored the views and experiences of parents and practitioners involved in the CATheter infections in CHildren (CATCH) trial, which allowed for deferred consent in certain circumstances. Design Mixed method survey, interview and focus group study. Participants 275 parents completed a questionnaire; 20 families participated in an interview (18 mothers, 5 fathers). 17 CATCH practitioners participated in one of four focus groups (10 nurses, 3 doctors and 4 clinical trial unit staff). Setting 12 UK childrens hospitals. Results Some parents were momentarily shocked or angered to discover that their child had or could have been entered into CATCH without their prior consent. Although these feelings resolved after the reasons why consent needed to be deferred were explained and that the CATCH interventions were already used in clinical care. Prior to seeking deferred consent for the first few times, CATCH practitioners were apprehensive, although their feelings abated with experience of talking to parents about CATCH. Parents reported that their decisions about their childs participation in the trial had been voluntary. However, mistiming the deferred consent discussion had caused distress for some. Practitioners and parents supported the use of deferred consent in CATCH and in future trials of interventions already used in clinical care. Conclusions Our study provides evidence to support the use of deferred consent in paediatric emergency medicine; it also indicates the crucial importance of practitioner communication and appropriate timing of deferred consent discussions.

The UK's gamete donor `crisis' - a critical analysis

Since April 2005, individuals donating sperm, eggs or embryos for the treatment of others in the UK have been required to agree to the disclosure of their identity to any child conceived as a result of their donation on reaching the age of 18. The main arguments advanced against the removal of donor anonymity are: first, it is responsible for a dramatic decline in the number of donors; second, it causes particular problems for donors in egg sharing programmes; and third, that it will increase the unwillingness of parents of donor-conceived children to tell their children about their conception. This paper analyses these arguments and points to flaws in both the evidential base and the argumentative strategies of these claims. The authors argue for a proactive approach to donor recruitment that reflects the contemporary context for the provision of donor conception services in the UK.

A survey of 1700 women who formed their families using donor spermatozoa

This paper reports the results of an online survey of 1700 recipients of donor spermatozoa conducted by the Donor Sibling Registry, aiming to understand the perspectives of respondents who had used donor spermatozoa. The survey examined: choice of sperm bank and donor; reporting of births and genetic disorders; disclosure; contact with donor and half-siblings; regulation of sperm donor activity and genetic testing; and access to medical information. The respondents formed three groups: single women; women in a same-sex relationship; and women in a heterosexual relationship. Some differences between the three cohorts were observed: preinsemination counselling; acceptance of donors without medical records or with chronic or late-onset diseases; awareness of choice of bank and type of donor; and views on the right of offspring to know their genetic origins. However, important areas of common ground were identified: the wish by those who had used an anonymous donor that they had used an open-identity donor; support for, and willingness to pay for, comprehensive genetic testing of donors; and desire for access to their donors family health information. The implications of these results for policies concerning the use and management of donor spermatozoa will be discussed. This paper reports the results of a survey of 1700 women who used donor spermatozoa to conceive a child. The survey considers their views on the following areas: choice of sperm bank and donor; reporting of births and genetic disorders; disclosure; contact with donor and half-siblings; regulation of sperm donor activity and genetic testing; and access to medical information. This was an online survey was designed and conducted by the Donor Sibling Registry (DSR), a US-based non-profit organization that supports donor sperm recipients, donors and donor-conceived people. The survey aimed to understand the experiences, perspectives and concerns of women who had used donor spermatozoa. The respondents formed three groups: single women; women in a same sex relationship; and women in a heterosexual relationship. Some differences between the three groups were observed: preinsemination counselling; acceptance of donors without medical records or with chronic or late-onset diseases; awareness of choice of bank and type of donor; and the right of offspring to know their genetic origins. However, despite these differences, important areas of common ground were identified: the wish by those who had used an anonymous donor that they had used an open-identity donor; support for, and a willingness to pay for, comprehensive genetic testing of donors; and desire for access to their donors family health information. The implications of these results for policies concerning the use and management of donor spermatozoa will be discussed.