The EU Clinical Trials Regulation: Key Priorities, Purposes and Aims and the Implications for Public Health

The replacement of the European Union (EU) Clinical Trials Directive by the new Clinical Trials Regulation (CTR), which entered into force on 16 June 2014 but will not apply before 28 May 2016, provides an opportunity to review the legal and political context within which this important aspect of research law and policy sits and to reflect on the implications for public health. My aim in this article is to relate the context to the key purposes and aims of EU law and policy on clinical trials in order to explain and clarify its orientation. On that basis, I argue that the CTR and the changes it introduces to the law on clinical trials are part of the EU's continued focus on market optimisation. It is this focus that orients and directs the wider pharmaceutical development pipeline, but that undermines the achievement of key public health objectives.

Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials

BACKGROUND: The task of revising dietary folate recommendations for optimal health is complicated by a lack of data quantifying the biomarker response that reliably reflects a given folate intake.

OBJECTIVE: We conducted a dose-response meta-analysis in healthy adults to quantify the typical response of recognized folate biomarkers to a change in folic acid intake.

DESIGN: Electronic and bibliographic searches identified 19 randomized controlled trials that supplemented with folic acid and measured folate biomarkers before and after the intervention in apparently healthy adults aged ≥18 y. For each biomarker response, the regression coefficient (β) for individual studies and the overall pooled β were calculated by using random-effects meta-analysis.

RESULTS: Folate biomarkers (serum/plasma and red blood cell folate) increased in response to folic acid in a dose-response manner only up to an intake of 400 μg/d. Calculation of the overall pooled β for studies in the range of 50 to 400 μg/d indicated that a doubling of folic acid intake resulted in an increase in serum/plasma folate by 63% (71% for microbiological assay; 61% for nonmicrobiological assay) and red blood cell folate by 31% (irrespective of whether microbiological or other assay was used). Studies that used the microbiological assay indicated lower heterogeneity compared with studies using nonmicrobiological assays for determining serum/plasma (I(2) = 13.5% compared with I(2) = 77.2%) and red blood cell (I(2) = 45.9% compared with I(2) = 70.2%) folate.

CONCLUSIONS: Studies administering >400 μg folic acid/d show no dose-response relation and thus will not yield meaningful results for consideration when generating dietary folate recommendations. The calculated folate biomarker response to a given folic acid intake may be more robust with the use of a microbiological assay rather than alternative methods for blood folate measurement.

Exploring the Findings from Three Randomised Controlled Trials of Bookgifting Programmes

Aims: This paper explores the effects from three similar bookgifting programmes on improving reading outcomes of early years’ children, their parents and teachers.
Methods: The paper draws on research data produced by the Centre for Effective Education during three randomised controlled trial (RCT) evaluations of bookgifting programmes (N=1694 participant families in total). The three studies used pre and post test measures to identify effects across a total of 15 social, cognitive and behavioural reading outcomes.
Results: The overall average effect across the 15 outcomes from data provided by 1694 participant families, was d=0.07. This is a relatively small overall effect and there was an overall pattern of small positive effects of this scale across the wide range of the reading outcomes assessed. However, only one significant effect was identified in the 15 outcomes assessed across all three studies.
Conclusions: The review of these three studies suggests that the RCTs struggle to identify significant effects in these low exposure and low cost bookgifting interventions. Furthermore, it is recommended that future RCT studies of this type of programme require very large sample sizes in the scale of 1000’s rather than 100’s to generate enough study power. Or alternatively, these programmes could be evaluated as a component part of more intensive reading interventions.

Improving the wellbeing of staff who work in palliative care settings: a systematic review of psychosocial interventions

Background: Staff in palliative care settings perform emotionally demanding roles which may lead to psychological distress including stress and burnout. Therefore, interventions have been designed to address these occupational risks.

Aim: To investigate quantitative studies exploring the effectiveness of psychosocial interventions that attempt to improve psychological wellbeing of palliative care staff.

Design: A systematic review was conducted according to methodological guidance from UK Centre for Reviews and Dissemination.

Data sources: A search strategy was developed based on the initial scans of palliative care studies. Potentially eligible research articles were identified by searching the following databases: CINAHL, MEDLINE (Ovid), PsycINFO and Web of Science. Two reviewers independently screened studies against pre-set eligibility criteria. To assess quality, both researchers separately assessed the remaining studies using the Quality Assessment Tool for Quantitative Studies.

Results: A total of 1786 potentially eligible articles were identified – nine remained following screening and quality assessment. Study types included two randomised controlled trials, two non-randomised controlled trial designs, four one-group pre–post evaluations and one process evaluation. Studies took place in the United States and Canada (5), Europe (3) and Hong Kong (1). Interventions comprised a mixture of relaxation, education, support and cognitive training and targeted stress, fatigue, burnout, depression and satisfaction. The randomised controlled trial evaluations did not improve psychological wellbeing of palliative care staff. Only two of the quasi-experimental studies appeared to show improved staff wellbeing although these studies were methodologically weak.

Conclusion: There is an urgent need to address the lack of intervention development work and high-quality research in this area.

Does this case hold the answer to one of the worse types of pain in medicine--that of loin pain haematuria syndrome (LPHS)

A patient with loin pain haematuria syndrome suffering chronic throbbing pulsing pain overlaid with prolonged periods of incapacitating colic and overnight vomiting was presented 10 months following diagnosis. Ultrasound was normal. No renal or ureteral stones, or filling defects were seen on CT. At cytoscopy, bladder and urethra were normal, and bloody urine effluxed from the left ureteric orifice. The ureters were normal at diagnosis, and developed new abutting non‐penetrating calcifications by 8 months. Pain episodes of complete incapacitating intensity of 2–4 h duration were reduced to 10 min with 5 mg crushed tadalafil administered at onset. If tadalafil was delayed to after onset, the original course of agony resulted. Daily tadalafil reduced loin pain intensity, but not the exacerbations. Tadalafil efficacy may indicate that the pain exacerbations are due to spasm of ureter smooth muscle. 5 mg tadalafil taken at onset alleviated severe loin pain exacerbations in this case of loin pain haematuria syndrome.

Knowledge representation for data integration and exploration in translational medicine

Tese de doutoramento, Informática (Bioinformática), Universidade de Lisboa, Faculdade de Ciências, 2014

Designing personalized video-based crossmedia informal learning environments beyond iTV

Tese de doutoramento, Informática (Engenharia Informática), Universidade de Lisboa, Faculdade de Ciências, 2014

Complex Interplay Between Determinants of Pacing and Performance During 20 km Cycle Time Trials

Purpose This study examined the determinants of pacing strategy and performance during self paced maximal exercise. Methods Eight well trained cyclists completed two 20 km time trials. Power output, RPE, positive and negative affect, and iEMG activity of the active musculature were recorded every 0.5km, confidence in achieving pre-exercise goals was assessed every 5 km, and blood lactate and pH were measured post-exercise. Differences in all parameters were assessed between fastest (FAST) and slowest (SLOW) trials performed. Results Mean power output was significantly higher during the initial 90% of FAST, but not the final 10%, and blood lactate concentration was significantly higher and pH significantly lower following FAST. Mean iEMG activity was significantly higher throughout SLOW. RPE was similar throughout both trials, but participants had significantly more positive affect and less negative affect throughout FAST. Participants grew less confident in their ability to achieve their goals throughout SLOW. Conclusions The results suggest that affect may be the primary psychological regulator of pacing strategy and that higher levels of positivity and lower levels of negativity may have been associated with a more aggressive strategy during FAST. Although the exact mechanisms through which affect acts to influence performance are unclear, it may determine the degree of physiological disruption that can be tolerated, or be reflective of peripheral physiological status in relation to the still to be completed exercise task.

Adipose stromal vascular fraction cell sheets as vascular strategies for tissue engineering and regenerative medicine applications

Tese de mestrado em Engenharia Biomédica e Biofísica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2015

Structural proteins of enveloped virus : from biochemistry to molecular medicine : a focus on dengue virus

Tese de doutoramento, Ciências Biomédicas (Bioquímica Médica), Universidade de Lisboa, Faculdade de Medicina, 2016