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Background: Conducting health impact assessments (HIAs) is a growing practice in various organizations and countries, yet scholarly interest in HIAs has primarily focused on the synergies between exposure and health outcomes. This limits our understanding of what factors influence HIAs and the uptake of their outcomes. This paper presents a framework for conducting participatory quantitative HIA (PQHIA) in low- and middle-income countries (LMICs), including integrating the outcomes back into society after an HIA is conducted. The study responds to the question: what are the different components of a participatory quantitative model that can influence HIA implementation in LMICs? Methods: To build the framework, we used a case study from a PQHIA fieldwork model developed in Port Louis (Mauritius). To explore thinking on the participatory components of the framework, we extract and analyze data from ethnographic material including fieldnotes, interviews, focus group discussions and feedback exercises with 14 stakeholders from the same case study. We confirm the validity of the ethnographic data using five quality criteria: credibility, transferability, dependability, confirmability, and authenticity. We build the PQHIA framework connecting the main HIA steps with factors influencing HIAs. Results: The final framework depicts the five standard HIA stages and summarizes participatory activities and outcomes. It also reflects key factors influencing PQHIA practice and uptake of HIA outcomes: costs for participation, HIA knowledge and interest of stakeholders, social responsibility of policymakers, existing policies, data availability, citizen participation, multi-level stakeholder engagement and multisectoral coordination. The framework suggests that factors necessary to complete a participatory HIA are the same needed to re-integrate HIA results back into the society. There are three different areas that can act as facilitators to PQHIAs: good governance, evidence-based policy making, and access to resources. Conclusions: The framework has several implications for research and practice. It underlines the importance of applying participatory approaches critically while providing a blueprint for methods to engage local stakeholders. Participatory approaches in quantitative HIAs are complex and demand a nuanced understanding of the context. Therefore, the political and cultural contexts in which HIA is conducted will define how the framework is applied. Finally, the framework underlines that participation in HIA does not need to be expensive or time consuming for the assessor or the participant. Yet, participatory quantitative models need to be contextually developed and integrated if they are to provide health benefits and be beneficial for the participants. This integration can be facilitated by investing in opportunities that fuel good governance and evidence-based policy making.

Background: Conducting health impact assessments (HIAs) is a growing practice in various organizations and countries, yet scholarly interest in HIAs has primarily focused on the synergies between exposure and health outcomes. This limits our understanding of what factors influence HIAs and the uptake of their outcomes. This paper presents a framework for conducting participatory quantitative HIA (PQHIA) in low- and middle-income countries (LMICs), including integrating the outcomes back into society after an HIA is conducted. The study responds to the question: what are the different components of a participatory quantitative model that can influence HIA implementation in LMICs?. Methods: To build the framework, we used a case study from a PQHIA fieldwork model developed in Port Louis (Mauritius). To explore thinking on the participatory components of the framework, we extract and analyze data from ethnographic material including fieldnotes, interviews, focus group discussions and feedback exercises with 14 stakeholders from the same case study. We confirm the validity of the ethnographic data using five quality criteria: credibility, transferability, dependability, confirmability, and authenticity. We build the PQHIA framework connecting the main HIA steps with factors influencing HIAs. Results: The final framework depicts the five standard HIA stages and summarizes participatory activities and outcomes. It also reflects key factors influencing PQHIA practice and uptake of HIA outcomes: costs for participation, HIA knowledge and interest of stakeholders, social responsibility of policymakers, existing policies, data availability, citizen participation, multi-level stakeholder engagement and multisectoral coordination. The framework suggests that factors necessary to complete a participatory HIA are the same needed to re-integrate HIA results back into the society. There are three different areas that can act as facilitators to PQHIAs: good governance, evidence-based policy making, and access to resources. Conclusions: The framework has several implications for research and practice. It underlines the importance of applying participatory approaches critically while providing a blueprint for methods to engage local stakeholders. Participatory approaches in quantitative HIAs are complex and demand a nuanced understanding of the context. Therefore, the political and cultural contexts in which HIA is conducted will define how the framework is applied. Finally, the framework underlines that participation in HIA does not need to be expensive or time consuming for the assessor or the participant. Yet, participatory quantitative models need to be contextually developed and integrated if they are to provide health benefits and be beneficial for the participants. This integration can be facilitated by investing in opportunities that fuel good governance and evidence-based policy making.

Background: Cities are an important driving force to implement the Sustainable Development Goals (SDGs) and the New Urban Agenda. The SDGs provide an operational framework to consider urbanization globally, while providing local mechanisms for action and careful attention to closing the gaps in the distribution of health gains. While health and well-being are explicitly addressed in SDG 3, health is also present as a pre condition of SDG 11, that aims at inclusive, safe, resilient and sustainable cities. Health in All Policies (HiAP) is an approach to public policy across sectors that systematically takes into account the health implications of decisions, seeks synergies, and avoids harmful health impacts in order to improve population health and health equity. HiAP is key for local decision-making processes in the context of urban policies to promote public health interventions aimed at achieving SDG targets. HiAPs relies heavily on the use of scientific evidence and evaluation tools, such as health impact assessments (HIAs). HIAs may include city-level quantitative burden of disease, health economic assessments, and citizen and other stakeholders' involvement to inform the integration of health recommendations in urban policies. The Barcelona Institute for Global Health (ISGlobal)'s Urban Planning, Environment and Health Initiative provides an example of a successful model of translating scientific evidence into policy and practice with regards to sustainable and healthy urban development. The experiences collected through ISGlobal's participation implementing HIAs in several cities worldwide as a way to promote HiAP are the basis for this analysis. Aim: The aim of this article is threefold: to understand the links between social determinants of health, environmental exposures, behaviour, health outcomes and urban policies within the SDGs, following a HiAP rationale; to review and analyze the key elements of a HiAP approach as an accelerator of the SDGs in the context of urban and transport planning; and to describe lessons learnt from practical implementation of HIAs in cities across Europe, Africa and Latin-America. Methods: We create a comprehensive, urban health related SDGs conceptual framework, by linking already described urban health dimensions to existing SDGs, targets and indicators. We discuss, taking into account the necessary conditions and steps to conduct HiAP, the main barriers and opportunities within the SDGs framework. We conclude by reviewing HIAs in a number of cities worldwide (based on the experiences collected by co-authors of this publication), including city-level quantitative burden of disease and health economic assessments, as practical tools to inform the integration of health recommendations in urban policies.Results: A conceptual framework linking SDGs and urban and transportplanning, environmental exposures, behaviour and health outcomes, following a HiAP rationale, is designed. We found at least 38 SDG targets relevant to urban health, corresponding to 15 SDGs, while 4 important aspects contained in our proposed framework were not present in the SDGs (physical activity, noise, quality of life or social capital). Thus, a more comprehensive HiAP vision within the SDGs could be beneficial. Our analysis confirmed that the SDGs framework provides an opportunity to formulate and implement policies with a HiAP approach. Three important aspects are highlighted: 1) the importance of the intersectoral work and health equity as a cross-cutting issue in sustainable development endeavors; 2) policy coherence, health governance, and stakeholders' participation as key issues; and 3) the need for high quality data. HIAs are a practical tool to implement HiAP. Opportunities and barriers related to the political, legal and health governance context, the capacity to inform policies in other sectors, the involvement of different stakeholders, and the availability of quality data are discussed based on our experience. Quantitative assessments can provide powerful data such as: estimates of annual preventable morbidity and disability-adjusted life-years (DALYs) under compliance with international exposure recommendations for physical activity, exposure to air pollution, noise, heat, and access to green spaces; the associated economic impacts in health care costs per year; and the number of preventable premature deaths when improvements in urban and transport planning are implemented. This information has been used to support the design of policies that promote cycling, walking, public, zero and lowemitting modes of transport, and the provision of urban greening or healthy public open spaces in Barcelona (e.g. Urban Mobility, Green Infrastructure and Biodiversity Plans, or the Superblocks's model), the Bus Rapid Transit and Open Streets initiatives in several Latin American cities or targeted SDGs assessments in Morocco. Conclusions: By applying tools such as HIA, HiAP can be implemented to inform and improve transport and urban planning to achieve the 2030 SDG Agenda. Such a framework could be potentially used in cities worldwide, including those of less developed regions or countries. Data availability, taking into account equity issues, strenghtening the communication between experts, decision makers and citizens, and the involvement of all major stakeholders are crucial elements for the HiAP approach to translate knowledge into SDG implementation.

BACKGROUND: Road traffic is the main source of environmental noise in European cities and one of the main environmental risks to health and wellbeing. In this study we aimed to provide an in-depth assessment of available road traffic noise data and to estimate population exposure and health impacts for cities in Europe. METHODS: We conducted the analysis for 724 cities and 25 greater cities in 25 European countries. We retrieved road traffic strategic noise maps delivered under the Environmental Noise Directive (END) or available from local sources. We assessed noise exposure using the 24 h day-evening-night noise level indicator (Lden) starting at exposure levels of 55 dB Lden - based on data availability - for the adult population aged 20 and over (n = 123,966,346). For the adults exposed to noise levels above 55 dB Lden we estimated the health impacts of compliance with the World Health Organization (WHO) recommendation of 53 dB Lden. Two primary health outcomes were assessed: high noise annoyance and Ischemic Heart Disease (IHD), using mortality from IHD causes as indicator. Exposure Response Functions (ERFs) relating road traffic noise exposure to annoyance and IHD mortality were retrieved from the literature. Uncertainties in input parameters were propagated using Monte Carlo simulations to obtain point estimates and empirical 95% Confidence Intervals (CIs). Lastly, the noise maps were categorized as high, moderate and low quality following a qualitative approach. RESULTS: Strategic noise map data was delivered in three distinct formats (i.e. raster, polygon or polyline) and had distinct noise ranges and levels of categorization. The majority of noise maps (i.e. 83.2%) were considered of moderate or low quality. Based on the data provided, almost 60 million adults were exposed to road traffic noise levels above 55 dB Lden, equating to a median of 42% (Interquartile Range (IQR): 31.8-64.8) of the adult population across the analysed cities. We estimated that approximately 11 million adults were highly annoyed by road traffic noise and that 3608 deaths from IHD (95% CI: 843-6266) could be prevented annually with compliance of the WHO recommendation. The proportion of highly annoyed adults by city had a median value of 7.6% (IQR: 5.6-11.8) across the analysed cities, while the number preventable deaths had a median of 2.2 deaths per 100,000 population (IQR: 1.4-3.1). CONCLUSIONS: Based on the provided strategic noise maps a considerable number of adults in European cities are exposed to road traffic noise levels harmful for health. Efforts to standardize the strategic noise maps and to increase noise and disease data availability at the city level are needed. These would allow for a more accurate and comprehensive assessment of the health impacts and further help local governments to address the adverse health effects of road traffic noise.

Background: Road traffic is the main source of environmental noise in European cities and one of the main environmental risks to health and wellbeing. In this study we aimed to provide an in-depth assessment of available road traffic noise data and to estimate population exposure and health impacts for cities in Europe. Methods: We conducted the analysis for 724 cities and 25 greater cities in 25 European countries. We retrieved road traffic strategic noise maps delivered under the Environmental Noise Directive (END) or available from local sources. We assessed noise exposure using the 24 h day-evening-night noise level indicator (Lden) starting at exposure levels of 55 dB Lden - based on data availability - for the adult population aged 20 and over (n = 123,966,346). For the adults exposed to noise levels above 55 dB Lden we estimated the health impacts of compliance with the World Health Organization (WHO) recommendation of 53 dB Lden. Two primary health outcomes were assessed: high noise annoyance and Ischemic Heart Disease (IHD), using mortality from IHD causes as indicator. Exposure Response Functions (ERFs) relating road traffic noise exposure to annoyance and IHD mortality were retrieved from the literature. Uncertainties in input parameters were propagated using Monte Carlo simulations to obtain point estimates and empirical 95% Confidence Intervals (CIs). Lastly, the noise maps were categorized as high, moderate and low quality following a qualitative approach. Results: Strategic noise map data was delivered in three distinct formats (i.e. raster, polygon or polyline) and had distinct noise ranges and levels of categorization. The majority of noise maps (i.e. 83.2%) were considered of moderate or low quality. Based on the data provided, almost 60 million adults were exposed to road traffic noise levels above 55 dB Lden, equating to a median of 42% (Interquartile Range (IQR): 31.8-64.8) of the adult population across the analysed cities. We estimated that approximately 11 million adults were highly annoyed by road traffic noise and that 3608 deaths from IHD (95% CI: 843-6266) could be prevented annually with compliance of the WHO recommendation. The proportion of highly annoyed adults by city had a median value of 7.6% (IQR: 5.6-11.8) across the analysed cities, while the number preventable deaths had a median of 2.2 deaths per 100,000 population (IQR: 1.4-3.1). Conclusions: Based on the provided strategic noise maps a considerable number of adults in European cities are exposed to road traffic noise levels harmful for health. Efforts to standardize the strategic noise maps and to increase noise and disease data availability at the city level are needed. These would allow for a more accurate and comprehensive assessment of the health impacts and further help local governments to address the adverse health effects of road traffic noise.

BACKGROUND: Undernutrition during pregnancy leads to low birthweight, poor growth and inter-generational undernutrition. We did a non-blinded cluster-randomised controlled trial in the plains districts of Dhanusha and Mahottari, Nepal to assess the impact on birthweight and weight-for-age z-scores among children aged 0-16 months of community-based participatory learning and action (PLA) women's groups, with and without food or cash transfers to pregnant women. METHODS: We randomly allocated 20 clusters per arm to four arms (average population/cluster = 6150). All consenting married women aged 10-49 years, who had not had tubal ligation and whose husbands had not had vasectomy, were monitored for missed menses. Between 29 Dec 2013 and 28 Feb 2015 we recruited 25,092 pregnant women to surveillance and interventions: PLA alone (n = 5626); PLA plus food (10 kg/month of fortified wheat-soya 'Super Cereal', n = 6884); PLA plus cash (NPR750≈US$7.5/month, n = 7272); control (existing government programmes, n = 5310). 539 PLA groups discussed and implemented strategies to improve low birthweight, nutrition in pregnancy and hand washing. Primary outcomes were birthweight within 72 hours of delivery and weight-for-age z-scores at endline (age 0-16 months). Only children born to permanent residents between 4 June 2014 and 20 June 2015 were eligible for intention to treat analyses (n = 10936), while in-migrating women and children born before interventions had been running for 16 weeks were excluded. Trial status: completed. RESULTS: In PLA plus food/cash arms, 94-97% of pregnant women attended groups and received a mean of four transfers over their pregnancies. In the PLA only arm, 49% of pregnant women attended groups. Due to unrest, the response rate for birthweight was low at 22% (n = 2087), but response rate for endline nutritional and dietary measures exceeded 83% (n = 9242). Compared to the control arm (n = 464), mean birthweight was significantly higher in the PLA plus food arm by 78·0 g (95% CI 13·9, 142·0; n = 626) and not significantly higher in PLA only and PLA plus cash arms by 28·9 g (95% CI -37·7, 95·4; n = 488) and 50·5 g (95% CI -15·0, 116·1; n = 509) respectively. Mean weight-for-age z-scores of children aged 0-16 months (average age 9 months) sampled cross-sectionally at endpoint, were not significantly different from those in the control arm (n = 2091). Differences in weight for-age z-score were as follows: PLA only -0·026 (95% CI -0·117, 0·065; n = 2095); PLA plus cash -0·045 (95% CI -0·133, 0·044; n = 2545); PLA plus food -0·033 (95% CI -0·121, 0·056; n = 2507). Amongst many secondary outcomes tested, compared with control, more institutional deliveries (OR: 1.46 95% CI 1.03, 2.06; n = 2651) and less colostrum discarding (OR:0.71 95% CI 0.54, 0.93; n = 2548) were found in the PLA plus food arm but not in PLA alone or in PLA plus cash arms. INTERPRETATION: Food supplements in pregnancy with PLA women's groups increased birthweight more than PLA plus cash or PLA alone but differences were not sustained. Nutrition interventions throughout the thousand-day period are recommended. TRIAL REGISTRATION: ISRCTN75964374.

Background: Undernutrition during pregnancy leads to low birthweight, poor growth and inter-generational undernutrition. We did a non-blinded cluster-randomised controlled trial in the plains districts of Dhanusha and Mahottari, Nepal to assess the impact on birthweight and weight-for-age z-scores among children aged 0–16 months of community-based participatory learning and action (PLA) women's groups, with and without food or cash transfers to pregnant women. Methods: We randomly allocated 20 clusters per arm to four arms (average population/cluster = 6150). All consenting married women aged 10–49 years, who had not had tubal ligation and whose husbands had not had vasectomy, were monitored for missed menses. Between 29 Dec 2013 and 28 Feb 2015 we recruited 25,092 pregnant women to surveillance and interventions: PLA alone (n = 5626); PLA plus food (10 kg/month of fortified wheat-soya 'Super Cereal', n = 6884); PLA plus cash (NPR750≈US$7.5/month, n = 7272); control (existing government programmes, n = 5310). 539 PLA groups discussed and implemented strategies to improve low birthweight, nutrition in pregnancy and hand washing. Primary outcomes were birthweight within 72 hours of delivery and weight-for-age z-scores at endline (age 0–16 months). Only children born to permanent residents between 4 June 2014 and 20 June 2015 were eligible for intention to treat analyses (n = 10936), while in-migrating women and children born before interventions had been running for 16 weeks were excluded. Trial status: completed. Results: In PLA plus food/cash arms, 94–97% of pregnant women attended groups and received a mean of four transfers over their pregnancies. In the PLA only arm, 49% of pregnant women attended groups. Due to unrest, the response rate for birthweight was low at 22% (n = 2087), but response rate for endline nutritional and dietary measures exceeded 83% (n = 9242). Compared to the control arm (n = 464), mean birthweight was significantly higher in the PLA plus food arm by 78·0 g (95% CI 13·9, 142·0; n = 626) and not significantly higher in PLA only and PLA plus cash arms by 28·9 g (95% CI -37·7, 95·4; n = 488) and 50·5 g (95% CI -15·0, 116·1; n = 509) respectively. Mean weight-for-age z-scores of children aged 0–16 months (average age 9 months) sampled cross-sectionally at endpoint, were not significantly different from those in the control arm (n = 2091). Differences in weight for-age z-score were as follows: PLA only -0·026 (95% CI -0·117, 0·065; n = 2095); PLA plus cash -0·045 (95% CI -0·133, 0·044; n = 2545); PLA plus food -0·033 (95% CI -0·121, 0·056; n = 2507). Amongst many secondary outcomes tested, compared with control, more institutional deliveries (OR: 1.46 95% CI 1.03, 2.06; n = 2651) and less colostrum discarding (OR:0.71 95% CI 0.54, 0.93; n = 2548) were found in the PLA plus food arm but not in PLA alone or in PLA plus cash arms. Interpretation: Food supplements in pregnancy with PLA women's groups increased birthweight more than PLA plus cash or PLA alone but differences were not sustained. Nutrition interventions throughout the thousand-day period are recommended.

Background Undernutrition during pregnancy leads to low birthweight, poor growth and inter-generational undernutrition. We did a non-blinded cluster-randomised controlled trial in the plains districts of Dhanusha and Mahottari, Nepal to assess the impact on birthweight and weight-for-age z-scores among children aged 0–16 months of community-based participatory learning and action (PLA) women's groups, with and without food or cash transfers to pregnant women. Methods We randomly allocated 20 clusters per arm to four arms (average population/cluster = 6150). All consenting married women aged 10–49 years, who had not had tubal ligation and whose husbands had not had vasectomy, were monitored for missed menses. Between 29 Dec 2013 and 28 Feb 2015 we recruited 25,092 pregnant women to surveillance and interventions: PLA alone (n = 5626); PLA plus food (10 kg/month of fortified wheat-soya 'Super Cereal', n = 6884); PLA plus cash (NPR750≈US$7.5/month, n = 7272); control (existing government programmes, n = 5310). 539 PLA groups discussed and implemented strategies to improve low birthweight, nutrition in pregnancy and hand washing. Primary outcomes were birthweight within 72 hours of delivery and weight-for-age z-scores at endline (age 0–16 months). Only children born to permanent residents between 4 June 2014 and 20 June 2015 were eligible for intention to treat analyses (n = 10936), while in-migrating women and children born before interventions had been running for 16 weeks were excluded. Trial status: completed. Results In PLA plus food/cash arms, 94–97% of pregnant women attended groups and received a mean of four transfers over their pregnancies. In the PLA only arm, 49% of pregnant women attended groups. Due to unrest, the response rate for birthweight was low at 22% (n = 2087), but response rate for endline nutritional and dietary measures exceeded 83% (n = 9242). Compared to the control arm (n = 464), mean birthweight was significantly higher in the PLA plus food arm by 78·0 g (95% CI 13·9, 142·0; n = 626) and not significantly higher in PLA only and PLA plus cash arms by 28·9 g (95% CI -37·7, 95·4; n = 488) and 50·5 g (95% CI -15·0, 116·1; n = 509) respectively. Mean weight-for-age z-scores of children aged 0–16 months (average age 9 months) sampled cross-sectionally at endpoint, were not significantly different from those in the control arm (n = 2091). Differences in weight for-age z-score were as follows: PLA only -0·026 (95% CI -0·117, 0·065; n = 2095); PLA plus cash -0·045 (95% CI -0·133, 0·044; n = 2545); PLA plus food -0·033 (95% CI -0·121, 0·056; n = 2507). Amongst many secondary outcomes tested, compared with control, more institutional deliveries (OR: 1.46 95% CI 1.03, 2.06; n = 2651) and less colostrum discarding (OR:0.71 95% CI 0.54, 0.93; n = 2548) were found in the PLA plus food arm but not in PLA alone or in PLA plus cash arms. Interpretation Food supplements in pregnancy with PLA women's groups increased birthweight more than PLA plus cash or PLA alone but differences were not sustained. Nutrition interventions throughout the thousand-day period are recommended. Trial registration ISRCTN75964374.

BACKGROUND: Undernutrition during pregnancy leads to low birthweight, poor growth and inter-generational undernutrition. We did a non-blinded cluster-randomised controlled trial in the plains districts of Dhanusha and Mahottari, Nepal to assess the impact on birthweight and weight-for-age z-scores among children aged 0-16 months of community-based participatory learning and action (PLA) women's groups, with and without food or cash transfers to pregnant women. METHODS: We randomly allocated 20 clusters per arm to four arms (average population/cluster = 6150). All consenting married women aged 10-49 years, who had not had tubal ligation and whose husbands had not had vasectomy, were monitored for missed menses. Between 29 Dec 2013 and 28 Feb 2015 we recruited 25,092 pregnant women to surveillance and interventions: PLA alone (n = 5626); PLA plus food (10 kg/month of fortified wheat-soya 'Super Cereal', n = 6884); PLA plus cash (NPR750≈US$7.5/month, n = 7272); control (existing government programmes, n = 5310). 539 PLA groups discussed and implemented strategies to improve low birthweight, nutrition in pregnancy and hand washing. Primary outcomes were birthweight within 72 hours of delivery and weight-for-age z-scores at endline (age 0-16 months). Only children born to permanent residents between 4 June 2014 and 20 June 2015 were eligible for intention to treat analyses (n = 10936), while in-migrating women and children born before interventions had been running for 16 weeks were excluded. Trial status: completed. RESULTS: In PLA plus food/cash arms, 94-97% of pregnant women attended groups and received a mean of four transfers over their pregnancies. In the PLA only arm, 49% of pregnant women attended groups. Due to unrest, the response rate for birthweight was low at 22% (n = 2087), but response rate for endline nutritional and dietary measures exceeded 83% (n = 9242). Compared to the control arm (n = 464), mean birthweight was significantly higher in the PLA plus food arm by 78·0 g (95% CI 13·9, 142·0; n = 626) and not significantly higher in PLA only and PLA plus cash arms by 28·9 g (95% CI -37·7, 95·4; n = 488) and 50·5 g (95% CI -15·0, 116·1; n = 509) respectively. Mean weight-for-age z-scores of children aged 0-16 months (average age 9 months) sampled cross-sectionally at endpoint, were not significantly different from those in the control arm (n = 2091). Differences in weight for-age z-score were as follows: PLA only -0·026 (95% CI -0·117, 0·065; n = 2095); PLA plus cash -0·045 (95% CI -0·133, 0·044; n = 2545); PLA plus food -0·033 (95% CI -0·121, 0·056; n = 2507). Amongst many secondary outcomes tested, compared with control, more institutional deliveries (OR: 1.46 95% CI 1.03, 2.06; n = 2651) and less colostrum discarding (OR:0.71 95% CI 0.54, 0.93; n = 2548) were found in the PLA plus food arm but not in PLA alone or in PLA plus cash arms. INTERPRETATION: Food supplements in pregnancy with PLA women's groups increased birthweight more than PLA plus cash or PLA alone but differences were not sustained. Nutrition interventions throughout the thousand-day period are recommended. TRIAL REGISTRATION: ISRCTN75964374.