Living with Phenylketonuria: lessons from the PKU community

Introduction: We report the practical, social and psychological issues of living with phenylketonuria (PKU) from one of the largest surveys that has been completed by both adults with PKU and parents/caregivers of children. Methods: In the UK, parents/caregivers of children and adults with PKU were invited to complete an online survey between November 2017 to January 2018 by the NSPKU (National Society for Phenylketonuria). Results: 631 participants (adults, n=338; parents/caregivers of children, n=293) with PKU completed the questionnaire. Problems experienced by children with PKU were: difficulty with maintaining focus (48%,n=114/236), educational difficulties (28%, n=67/236), anxiety or depression (29%, n=68/236), and gastrointestinal symptoms (34%, n=97/282). Fifty one per cent (n=120/236) described social exclusion; 17% (n=41/236) had relationship issues with friends or family. Problems experienced by adults were: depression or anxiety (52%, n=148/286), difficulty maintaining focus (54%, n=154/286), and low mood (54%, n=180/334). Difficulties were experienced with relationships (34%, n=96/286); social exclusion (44%, n=126/286); and gastrointestinal issues (n=34%, n=112/334). Common medications used included antidepressants (40%, n=131/331) and anxiolytics (18%, n=60/334). Discussions: Adults with PKU or caregivers/parents of children identified significant neurocognitive, mental health and general health issues. Limits on socialisation, perception of social isolation and dietary stigma are major obstacles which are difficult to overcome with conventional dietary management

How Can the Evidence from Global Large-scale Clinical Trials for Cardiovascular Diseases be Improved?

<p>Abstract</p> <p>Background</p> <p>Clinical investigations are important for obtaining evidence to improve medical treatment. Large-scale clinical trials with thousands of participants are particularly important for this purpose in cardiovascular diseases. Conducting large-scale clinical trials entails high research costs. This study sought to investigate global trends in large-scale clinical trials in cardiovascular diseases.</p> <p>Findings</p> <p>We searched for trials using clinicaltrials.gov (URL: <url>http://www.clinicaltrials.gov/</url>) using the key words 'cardio' and 'event' in all fields on 10 April, 2010. We then selected trials with 300 or more participants examining cardiovascular diseases. The search revealed 344 trials that met our criteria. Of 344 trials, 71% were randomized controlled trials, 15% involved more than 10,000 participants, and 59% were funded by industry. In RCTs whose results were disclosed, 55% of industry-funded trials and 25% of non-industry funded trials reported statistically significant superiority over control (p = 0.012, 2-sided Fisher's exact test).</p> <p>Conclusions</p> <p>Our findings highlighted concerns regarding potential bias related to funding sources, and that researchers should be aware of the importance of trial information disclosures and conflicts of interest. We should keep considering management and training regarding information disclosures and conflicts of interest for researchers. This could lead to better clinical evidence and further improvements in the development of medical treatment worldwide.</p

Funding and infrastructure among large-scale clinical trials examining cardiovascular diseases in Japan: evidence from a questionnaire survey

<p>Abstract</p> <p>Background</p> <p>Large-scale clinical trials with thousands of participants are often needed to evaluate the risk reductions of cardiac events and/or death. Many recent clinical trials have evaluated the incidences of cardiac events using hard endpoints, especially in cardiovascular and metabolic medicine. A high investigation cost is involved in conducting a large-scale clinical trial, and obtaining sufficient funding is essential. The infrastructural environment of clinical trials is currently inadequate in Japan. We conducted a questionnaire-based survey to address this issue. The present study sought to clarify the current situation surrounding large-scale clinical trials in terms of funding and infrastructure, and to inform discussion about improving the financial and infrastructural situation for clinical trials.</p> <p>Methods</p> <p>We sent questionnaires to 119 sponsors of large-scale clinical trials between August 2007 and December 2007, and between July 2009 and August 2009. Answers to each question were summarized and data were statistically analyzed.</p> <p>Results</p> <p>We received responses from the sponsors of 63 (52.9%) out of 119 trials to which questionnaires were sent. The results revealed that 25 trials (39.7%) were funded by foundations, and 21 trials (33.3%) were funded by public agencies. All of the foundations involved in conducting clinical trials, where funding sources were specified, were funded by private organizations such as pharmaceutical companies. All of the clinical trials with a cost of JPY 300 million (USD 3.27 million) or more were funded by private organizations, and none were funded solely by public agencies. The sponsors of 23 trials (36.5%) responded that the trial was 'not registered' to clinical trial registry.</p> <p>Conclusions</p> <p>The questionnaire responses revealed that there were still many trials whose funding sources were unclear and many sponsors were unaware of their responsibilities in managing and/or financing the costs of clinical trials. These findings indicate that further discussion is required to establish appropriate frameworks and/or rules regarding funding, while considering conflicts of interest. This discussion should take place as soon as possible to facilitate appropriate clinical trials.</p

Adult domiciliary oxygen therapy. Position statement of the Thoracic Society of Australia and New Zealand

The document attached has been archived with permission from the editor of the Medical Journal of Australia (26 April 2007). An external link to the publisher’s copy is included.• Patients with chronic obstructive pulmonary disease and a stable daytime PaO2 of ≤55 mmHg (7.3kPa) live longer and have a better quality of life if provided with long-term continuous oxygen therapy. • It is reasonable to offer continuous oxygen therapy also to patients with other lung diseases that cause chronic hypoxaemia. • Indications for supplemental oxygen therapy during exercise (ambulatory oxygen therapy) and sleep (nocturnal oxygen therapy) are less clear.Christine F McDonald, Alan J Crockett and Iven H Youn

Reporting interventions in communication partner training: a critical review and narrative synthesis of the literature

Background: Communication partner training (CPT) is an umbrella term for a complex behavioural intervention for communications partners (CPs) of people with aphasia (PWA) and possibly PWA themselves, with many interacting components, deployed in flexible ways. Recent systematic reviews (Simmons-Mackie, Raymer, Armstrong, Holland, & Cherney, 2010; Simmons-Mackie, Raymer, & Cherney, 2016) have highlighted the effectiveness of CPT in addressing the skills of conversation partners and the communicative participation of people with aphasia but have suggested that CPT has been variably delivered, with no clear picture of what the essential elements of CPT are and how CPT is expected to achieve its results through hypothesised mechanisms of change (Coster, 2013). Aim: This paper aims broadly to consider specification of CPT and describes how CPT has been conducted overall and in relation to treatment recipients. Recommendations for CPT and areas for future research are considered. Methods & Procedures: A critical review and narrative synthesis was carried out through: (i) the systematic application of the 12-item TIDieR checklist (Hoffmann et al., 2014) to the 56 studies appraised in the Simmons-Mackie et al. (2010, 2016)) reviews, providing a quantitative overview of the completeness of CPT intervention reporting; and (ii) a qualitative synthesis of the reviewed CPT literature according to TIDieR items. Outcomes & Results: Half of the TIDieR checklist items were reported by 71% or more of the studies, and the rest of the items were reported by 0–63% of studies. TIDieR items relating to the treatment (goal, rationale or theory of essential elements, materials and procedures) and provision (provider, mode, timing, dose) were more frequently reported; however, the level of detail provided was often inadequate or incomplete. The interventions were insufficiently specified to enable replication for most of the studies considered. The most infrequently reported items were: name, location, intervention tailoring and modification, and planned and actual intervention adherence/fidelity. Conclusion: For a better understanding of an intervention, it is necessary to identify and describe potentially central elements and perhaps especially in complex interventions as CPT, where it is likely also more difficult. Whilst the reviewed CPT studies are on average reporting on slightly more than half of the TIDieR items, they are overall insufficiently detailed. Some items appear easier to report on, whereas other items have not been attended to, are too complex in nature to give a full report on, or simply have not been relevant for the individual study to include

Do mixed histological features affect survival benefit from neoadjuvant platinum‐based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group‐Directed Intergroup Study (S8710)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86993/1/j.1464-410X.2010.09900.x.pd

Informative noncompliance in endpoint trials

Noncompliance with study medications is an important issue in the design of endpoint clinical trials. Including noncompliant patient data in an intention-to-treat analysis could seriously decrease study power. Standard methods for calculating sample size account for noncompliance, but all assume that noncompliance is noninformative, i.e., that the risk of discontinuation is independent of the risk of experiencing a study endpoint. Using data from several published clinical trials (OPTIMAAL, LIFE, RENAAL, SOLVD-Prevention and SOLVD-Treatment), we demonstrate that this assumption is often untrue, and we discuss the effect of informative noncompliance on power and sample size

Methodological issues in the design and evaluation of supported communication for aphasia training: a cluster-controlled feasibility study

Objective: To assess the feasibility and acceptability of training stroke service staff to provide supported communication for people with moderate-severe aphasia in the acute phase; assess the suitability of outcome measures; collect data to inform sample size and Health Economic evaluation in a definitive trial. Design: Phase II cluster-controlled, observer-blinded feasibility study Settings: In-patient stroke rehabilitation units in the UK matched for bed numbers and staffing were assigned to control and intervention conditions. Participants: Seventy stroke rehabilitation staff from all professional groups, excluding doctors, were recruited. Twenty patients with moderate-severe aphasia were recruited. Intervention: Supported communication for aphasia training, adapted to the stroke unit context vs usual care. Training was supplemented by a staff learning log, refresher sessions and provision of communication resources. Main outcome measures: Feasibility of recruitment and acceptability of the intervention and of measures required to assess outcomes and Health Economic evaluation in a definitive trial. Staff outcomes: Measure of Support in Conversation; patient outcomes: Stroke and Aphasia Quality of Life Scale; Communicative Access Measure for Stroke; Therapy Outcome Measures for aphasia; EQ-5D-3L was used to assess health outcomes. Results: Feasibility of staff recruitment was demonstrated. Training in the intervention was carried out with 28 staff and was found to be acceptable in qualitative reports. Twenty patients consented to take part, 6 withdrew. Eighteen underwent all measures at baseline; 16 at discharge; and 14 at 6-month follow-up. Of 175 patients screened 71% were deemed to be ineligible, either lacking capacity or too unwell to participate. Poor completion rates impacted on assessment of patient outcomes. We were able to collect sufficient data at baseline, discharge and follow-up for economic evaluation. Conclusions: The feasibility study informed components of the intervention and implementation in day-to-day practice. Modifications to the design are needed before a definitive cluster-randomised trial can be undertaken