Barriers and Opportunities for WHO "Best Buys" Non-communicable Disease Policy Adoption and Implementation From a Political Economy Perspective: A Complexity Systematic Review.

BACKGROUND: Improving the adoption and implementation of policies to curb non-communicable diseases (NCDs) is a major challenge for better global health. The adoption and implementation of such policies remain deficient in various contexts, with limited insights into the facilitating and inhibiting factors. These policies have traditionally been treated as technical solutions, neglecting the critical influence of political economy dynamics. Moreover, the complex nature of these interventions is often not adequately incorporated into evidence for policy-makers. This study aims to systematically review and evaluate the factors affecting NCD policy adoption and implementation. METHODS: We conducted a complex systematic review of articles discussing the adoption and implementation of World Health Organization's (WHO's) "best buys" NCD policies. We identified political economy factors and constructed a causal loop diagram (CLD) program theory to elucidate the interplay between factors influencing NCD policy adoption and implementation. A total of 157 papers met the inclusion criteria. RESULTS: Our CLD highlights a central feedback loop encompassing three vital variables: (1) the ability to define, (re)shape, and pass appropriate policy into law; (2) the ability to implement the policy (linked to the enforceability of the policy and to addressing NCD local burden); and (3) ability to monitor progress, evaluate and correct the course. Insufficient context-specific data impedes the formulation and enactment of suitable policies, particularly in areas facing multiple disease burdens. Multisectoral collaboration plays a pivotal role in both policy adoption and implementation. Effective monitoring and accountability systems significantly impact policy implementation. The commercial determinants of health (CDoH) serve as a major barrier to defining, adopting, and implementing tobacco, alcohol, and diet-related policies. CONCLUSION: To advance global efforts, we recommend focusing on the development of robust accountability, monitoring, and evaluation systems, ensuring transparency in private sector engagement, supporting context-specific data collection, and effectively managing the CDoH. A system thinking approach can enhance the implementation of complex public health interventions.

Multisectoral action to address noncommunicable diseases: lessons from three country case studies.

Introduction: Multisectoral action is a central component of the global response to the rising prevalence of non-communicable diseases (NCDs). In this paper we aimed to unpack the definition of multisectoral action and provide an overview of the historical context, challenges, and recommendations alongside three country case studies: salt reduction in the UK, tobacco legislation in Nigeria, and regulation of edible oils in Iran. Methods: We used an iterative review process to select three country case studies from a list of 20 potential cases previously identified by WHO. At our third round of review we unanimously agreed to focus on salt reduction in the UK, tobacco regulation in Nigeria, and edible oil regulation in Iran as these represented rich cases on diverse risk factors from three different world regions that we felt offered important lessons. We conducted literature reviews to identify further data for each case study. Results: Across the three studies a number of important themes emerged. We found that multisectoral approaches demand the often difficult reconciliation of competing and conflicting values and priorities. Across our three chosen cases, commercial interests and free trade agreements were the most common obstacles to successful multisectoral strategies. We found that early consultative stakeholder engagement and strong political and bureaucratic leadership were necessary for success. Discussion: The complex multi-rooted nature of NCDs requires a multisectoral approach, but the inevitable conflicts that this entails requires careful navigation.

Engaging with the Private Sector for Noncommunicable Disease Prevention and Control: Is it Possible to Create "Shared Value?"

Noncommunicable diseases (NCDs) are the leading cause of premature mortality worldwide. Corporate interests are sometimes well-aligned with public health, but profiteering from the consumption of products that are known to be the major contributors to the noncommunicable disease burden undermines public health. This paper describes the key industry actors shaping the NCD landscape; highlights the unhealthy commodities' impact on health and the growing burden of NCDs; and outlines challenges and opportunities to reduce exposure to those risk factors. Corporations deploy a wide array of strategies to maximize profits at the expense of health, including sophisticated marketing techniques, interference in the policy-making process, opposition and distortion of research and evidence, and whitewashing of health-harming activities through corporate social responsibility initiatives. There can be no shared value for industries that sell goods that harm health irrespective of consumption patterns (such as tobacco and likely alcohol), so government actions such as regulation and legislation are the only viable policy instruments. Where shared value is possible (for example, with the food industry), industry engagement can potentially realign corporate interests with the public health interest for mutual benefit. Deliberate, careful, and nuanced approaches to engagement are required.

Non-communicable disease policy implementation from 2014 to 2021: a repeated cross-sectional analysis of global policy data for 194 countries.

BACKGROUND: Non-communicable diseases (NCDs) are the world's leading cause of death and disability. Global implementation of WHO-recommended NCD policies has been increasing with time, but in 2019 fewer than half of these policies had been implemented globally. In 2022, WHO released updated data on NCD policy implementation, on the basis of surveys conducted in 2021 during the COVID-19 pandemic. We sought to examine whether the trajectory of global policy implementation changed during this period. METHODS: In this repeated cross-sectional analysis, we used data from the 2015, 2017, 2020, and 2022 WHO progress monitors to calculate NCD policy implementation scores for all 194 WHO member states. We used Welch's ANOVA and Games-Howell post-hoc pairwise testing to examine changes in mean implementation scores for 19 WHO-recommended NCD policies, with assessment at the global, geographical, geopolitical, and country-income levels. We collated sales data on tobacco, alcohol, and junk foods to examine the association between changes in sales and the predicted probability of implementation of policies targeting these products. We also calculated the Corporate Financial Influence Index (CFII) for each country, which was used to assess the association between corporate influence and policy implementation. We used logistic regression to assess the relationship between product sales and the probability of implementing related policies. The relationship between CFII and policy implementation was assessed with Pearson's correlation analysis and random-effects multivariate regression. FINDINGS: Across the 194 countries, in the years preceding publication of each progress monitor, mean total policy implementation score (out of a potential 18·0) was 7·0 (SD 3·5) in 2014, 8·2 (3·5) in 2016, 8·6 (3·6) in 2019, and 8·6 (3·6) in 2021. Only the differences in mean implementation score between 2014 and the other three report years were deemed statistically significant (pairwise p<0·05). Thus the steady improvement in mean global NCD policy implementation stalled in 2021 at 47·8%. However, from 2019 to 2021, we identified shifts in individual policies: global mean implementation scores increased for policies on tobacco, clinical guidelines, salt, and child food marketing, and decreased for policies on alcohol, breastmilk substitute marketing, physical activity mass media campaigns, risk factor surveys, and national NCD plans and targets. Six of the seven policies with the lowest levels of implementation (global mean score <0·4 out of a potential 1·0) in both 2019 and 2021 were related to tobacco, alcohol, and unhealthy food. From 2020 onwards, we identified weak or no associations between sales of tobacco, alcohol, and junk foods and the predicted probability of implementing policies related to each commodity. Country-level CFII was significantly associated with total policy implementation score (Pearson's r -0·49, 95% CI -0·59 to -0·36), and this finding was supported in multivariate modelling for all policies combined and for all commercial policies except alcohol policies. INTERPRETATION: NCD policy implementation has stagnated. Progress in the implementation of some policies is matched by decreased implementation of others, particularly those related to unhealthy commodities. To prevent NCDs and their consequences, and attain the Sustainable Development Goals, the rate of NCD policy adoption must be substantially and urgently increased before the next NCD progress monitor and UN high-level meeting on NCDs in 2024. FUNDING: None.

US and EU Free Trade Agreements and implementation of policies to control tobacco, alcohol, and unhealthy food and drinks: A quasi-experimental analysis.

BACKGROUND: Identifying and tackling the factors that undermine regulation of unhealthy commodities is an essential component of effective noncommunicable disease (NCD) prevention. Unhealthy commodity producers may use rules in US and EU Free Trade Agreements (FTAs) to challenge policies targeting their products. We aimed to test whether there was a statistical relationship between US and EU FTA participation and reduced implementation of WHO-recommended policies. METHODS AND FINDINGS: We performed a statistical analysis assessing the probability of at least partially implementing 10 tobacco, alcohol, and unhealthy food and drink policies in 127 countries in 2014, 2016, and 2019. We assessed differences in implementation of these policies in countries with and without US/EU FTAs. We used matching to conduct 48 covariate-adjusted quasi-experimental comparisons across 27 matched US/EU FTA members (87 country-years) and performed additional analyses and robustness checks to assess alternative explanations for our results. Out of our 48 tests, 19% (9/48) identified a statistically significant decrease in the predicted probability of at least partially implementing the unhealthy commodity policy in question, while 2% (1/48) showed an increase. However, there was marked heterogeneity across policies. At the level of individual policies, US FTA participation was associated with a 37% reduction (95%CI: -0.51 to -0.22) in the probability of fully implementing graphic tobacco warning policies, and a 53% reduction (95%CI: -0.63 to -0.43) in the probability of at least partially implementing smoke-free place policies. EU FTA participation was associated with a 28% reduction (95%CI: -0.45 to -0.10) in the probability of fully implementing graphic tobacco warning policies, and a 25% reduction (95%CI: -0.47 to -0.03) in the probability of fully implementing restrictions on child marketing of unhealthy food and drinks. There was a positive association with implementing fat limits and bans, but this was not robust. Associations with other outcomes were not significant. The main limitations included residual confounding, limited ability to discern precise mechanisms of influence, and potentially limited generalisability to other FTAs. CONCLUSIONS: US and EU FTA participation may reduce the probability of implementing WHO-recommended tobacco and child food marketing policies by between a quarter and a half-depending on the FTA and outcome in question. Governments negotiating or participating in US/EU FTAs may need to establish robust health protections and mitigation strategies to achieve their NCD mortality reduction targets.

Study protocol: assessing the association between corporate financial influence and implementation of policies to tackle commercial determinants of non-communicable diseases: a cross-sectional analysis of 172 countries.

INTRODUCTION: There are many case studies of corporations that have worked to undermine health policy implementation. It is unclear whether countries that are more exposed to corporate financial influence are systematically less likely to implement robust health policies that target firms' financial interests. We aim to assess the association between corporate financial influence and implementation of WHO-recommended policies to constrain sales, marketing and consumption of tobacco, alcohol and unhealthy foods. METHODS AND ANALYSIS: We will perform a cross-sectional analysis of 172 WHO Member States using national datasets from 2015, 2017 and 2020. We will use random effects generalised least squares regression to test the association between implementation status of 12 WHO-recommended tobacco, alcohol and diet policies, and corporate financial influence, a metric that combines disclosure of campaign donations, public campaign finance, corporate campaign donations, legislature corrupt activities, disclosure by politicians and executive oversight. We will control for GDP per capita, population aged >65 years (%), urbanisation (%), level of democracy, continent, ethno-linguistic fractionalisation, legal origin, UN-defined 'Small Island Developing States' and Muslim population (%) (to capture alcohol policy differences). We will include year dummies to address the possibility of a spurious relationship between the outcome variable and the independent variables of interests. For example, there may be an upward global trend in policy implementation that coincides with an upward global trend in the regulation of lobbying and campaign finance. ETHICS AND DISSEMINATION: As this study uses publicly available data, ethics approval is not required. The authors have no conflicts of interest to declare. Findings will be submitted to a peer-reviewed journal for publication in the academic literature. All data, code and syntax will be made publicly available on GitHub.

Microsurgical Reconstruction for Reanimation of Foot Dorsiflexion in Children.

Foot drop is a debilitating condition, which causes physical disability and psychological challenges associated with difficulties walking. We report the indications, novel technique, and successful outcomes of two children (three limbs) who underwent free functional gracilis muscle transfers coaptated to the common peroneal nerve to reanimate active foot dorsiflexion and correct foot drop secondary to loss of the anterior compartment.

Assessing the association between Corporate Financial Influence and implementation of policies to tackle commercial determinants of non-communicable diseases: A cross-sectional analysis of 172 countries.

OBJECTIVE: Non-communicable diseases (NCDs) are the leading cause of global death and disability. Tobacco, alcohol, and unhealthy foods are major contributing risk factors. WHO Member States have unanimously endorsed a set of 12 policies designed to constrain the sale of these commodities, however, there are myriad case studies of commercial entities seeking to undermine effective legislation in order to protect their profits. We set out to quantify the association between corporate financial influence and implementation of commercial policies. METHODS: We generated policy implementation scores for all 194 WHO Member States using data from the 2015, 2017, and 2020 WHO NCD Progress Monitor Reports. We used publicly available data to create a novel Corporate Financial Influence Index (CFII) that quantifies the opportunity for corporations to use their financial resources to directly influence policymaking in each country. We reported policy implementation trends over time and used random effects multivariate regression to test the association between policy implementation and CFII for each country, while controlling for broad set of economic, cultural, historical, geographic, and demographic factors. FINDINGS: Implementation of the 12 WHO-backed commercial policies has risen over time, but remains low at approximately 40%. Progress is reversing for alcohol policies. CFII explains around a fifth of the variance in global implementation. For every 10% rise in CFII, implementation falls by approximately 2% (95%CI 0.90 to 3.5, p < 0.001). CONCLUSION: Our quantitative global analysis suggests that financial corporate influence is negatively associated with implementation of policies that seek to restrict the marketing, sale, and consumption of unhealthy (but profitable) commodities. In the context of anemic international progress tackling NCDs, greater attention should be paid to managing regulatory opportunities for overt and covert corporate financial influence as a core plank of the global NCD response.

Non-communicable disease policy implementation in Libya: A mixed methods assessment.

The Libyan Ministry of Health is keen to understand how it can introduce policies to protect its population from non-communicable diseases (NCDs). We aimed to perform an implementation research assessment of the current situation, including challenges and opportunities. We used an explanatory sequential mixed methods design. We started with a quantitative assessment of NCD policy performance based on review of the WHO NCD Progress Monitor Reports. Once we had identified Libya's NCD policy gaps we performed a systematic review to identify international lessons around barriers and successful strategies for the policies Libya has not yet implemented. Finally, we performed a series of key stakeholder interviews with senior policymakers to explore their perspectives around promising policy actions. We used a realist paradigm, methods triangulation, and a joint display to synthesise the interpretation of our findings and develop recommendations. Libya has not fully implemented any of the recommended policies for diet, physical activity, primary care guidelines & therapeutics, or data collection, targets & surveillance. It does not have robust tobacco policies in place. Evidence from the international literature and policymaker interviews emphasised the centrality of according strong political leadership, governance structures, multisectoral engagement, and adequate financing to policy development activities. Libya's complex political and security situation are major barriers for policy implementation. Whilst some policies will be very challenging to develop and deploy, there are a number of simple policy actions that could be implemented with minimum effort; from inviting WHO to conduct a second STEPS survey, to signing the international code on breast-milk substitutes. Like many other fragile and conflict-affected states, Libya has not accorded NCDs the policy attention they demand. Whilst strong high-level leadership is the ultimate key to providing adequate protections, there are a range of simple measures that can be implemented with relative ease.

Multidisciplinary reconstructive management of residual recalcitrant empyema cavity: A retrospective observational cohort study.

BACKGROUND: Patients with stage III empyema require chest wall fenestration to enable lung re-expansion and continuous drainage of the persisting empyema cavity. This chronic wound negatively affects patients' exercise tolerance, ability to carry out activities of daily living, and quality of life. METHODS: Eight consecutive patients underwent chest wall reconstruction following fenestration and were followed up over a minimum of 12 months. This study included adult patients (over 18 years of age). There were no exclusion criteria. Data were collected retrospectively. RESULTS: Eight patients (six male and two female), with a mean age of 56 years (range, 22-76), were included. All of them had comorbidities including history of neoplasia (n = 6), atrial fibrillation (n = 3), and hypertension (n = 2). Aetiology of empyema included lung cancer resection complicated by bronchopleural fistula (n = 4), pneumonia (n = 2), and pleural effusion (n = 2). Five patients had a low metabolic reserve evident by a low BMI (range, 16-22), and a median malnutrition universal screen tool (MUST) score of 2 (range, 1-4). Following intensive infection control and nutritional support, patients underwent reconstruction 11 months (median; range 5-51) after fenestration. Seven patients were followed up and had no recurrence of empyema and bronchopleural fistula. They all reported significant improvements in their quality of life, and their Eastern Cooperative Oncology Group (ECOG) performance status improved from three to one. One patient died 56 days post-reconstruction from cardiorespiratory failure, which required readmission to hospital. CONCLUSION: We demonstrate that free tissue reconstruction including multidisciplinary input and optimisation at all stages of care successfully closes residual recalcitrant empyema cavity without recurrence and leads to significant improvements in the quality of life.

Implementation of non-communicable disease policies from 2015 to 2020: a geopolitical analysis of 194 countries.

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality globally. We aimed to analyse trends in implementation of WHO-recommended population-level policies and associations with national geopolitical characteristics. METHODS: We calculated cross-sectional NCD policy implementation scores for all 194 WHO member states from the 2015, 2017, and 2020 WHO progress monitor reports, and examined changes over time as well as average implementation by geographical and geopolitical region and income level. We developed a framework of indicators of national characteristics hypothesised to influence policy implementation, including democracy, corporate permeation (an indicator of corporate influence), NCD burden, and risk factor prevalence. We used multivariate regression models to test our hypotheses. FINDINGS: On average, countries had fully implemented a third (32·8%, SD 18·2) of the 19 policies in 2020. Using aggregate policy scores, which include partially implemented policies, mean implementation had increased from 39·0% (SD 19·3) in 2015 to 45·9% (19·2) in 2017 and 47·0% (19·8) in 2020. Implementation was lowest for policies relating to alcohol, tobacco, and unhealthy foods, and had reversed for a third of all policies. Low-income and less democratic countries had the lowest policy implementation. Our model explained 64·8% of variance in implementation scores. For every unit increase in corporate permeation, implementation decreased by 5·0% (95% CI -8·0 to -1·9, p=0·0017), and for every 1% increase in NCD mortality burden, implementation increased by 0·9% (0·2 to 1·6, p=0·014). Democracy was positively associated with policy implementation, but only in countries with low corporate permeation. INTERPRETATION: Implementation of NCD policies is uneven, but broadly improving over time. Urgent action is needed to boost implementation of policies targeting corporate vectors of NCDs, and to support countries facing high corporate permeation. FUNDING: The National Institutes for Health Research, the Swedish Research Council, the Fulbright Commission, and the Swedish Society of Medicine.

Sterol Biosynthesis Inhibition in Pregnant Women Taking Prescription Medications.

Sterol biosynthesis is a critical homeostatic mechanism of the body. Sterol biosynthesis begins during early embryonic life and continues throughout life. Many commonly used medications, prescribed >200 million times in the United States annually, have a sterol biosynthesis inhibition side effect. Using our high-throughput LC-MS/MS method, we assessed the levels of post-lanosterol sterol intermediates (lanosterol, desmosterol, and 7-dehydrocholesterol (7-DHC)) and cholesterol in 1312 deidentified serum samples from pregnant women. 302 samples showing elevated 7-DHC were analyzed for the presence of 14 medications known to inhibit the 7-dehydrocholesterol reductase enzyme (DHCR7) and increase 7-DHC. Of the 302 samples showing 7-DHC elevation, 43 had detectable levels of prescription medications with a DHCR7-inhibiting side effect. Taking more than one 7-DHC-elevating medication in specific combinations (polypharmacy) might exacerbate the effect on 7-DHC levels in pregnant women, suggesting a potentially additive or synergistic effect. As 7-DHC and 7-DHC-derived oxysterols are toxic, and as DHCR7-inhibiting medications are considered teratogens, our findings raise potential concerns regarding the use of prescription medication with a DHCR7-inhibiting side effect during pregnancy. The use of prescription medications during pregnancy is sometimes unavoidable, but choosing a medication without a DHCR7-inhibiting side effect might lead to a heathier pregnancy and prevent putatively adverse outcomes for the developing offspring.

Estimating the impact of achieving Turkey's non-communicable disease policy targets: A macro-simulation modelling study.

BACKGROUND: The Burden of non-communicable disease (NCDs) has continued to rise globally, particularly in low- and middle-income countries. In Turkey, NCDs account for 89% of all deaths, with nearly one in five deaths occurring before age 70. This study investigates the number of NCD deaths that could be prevented if Turkey met national and international targets for major modifiable NCD risk factors. METHODS: Preventable deaths were estimated using the World Health Organization (WHO) 'Preventable Risk Integrated ModEl' (PRIME), by combining: 1) Baseline exposure data for risk factors, referenced from national surveillance and cohort studies; 2) Aetiological associations from published meta-analyses; and 3) Demographic and mortality statistics obtained from the Turkish Statistical Institute (TurkStat). Confidence intervals were estimated using Monte Carlo simulations. FINDINGS: If Turkey met its NCD risk factor targets for reducing tobacco and salt consumption by 30%, and physical inactivity by 10% in 2017, an estimated 19,859 deaths (95%CI: 12,802 to 26,609) could have been prevented. Approximately two thirds of these preventable deaths were in men, and one in three were in adults below 75 years. A 30% relative reduction in the consumption of alcohol, tobacco, and salt, as well as physical inactivity, would prevent 180 (107 to 259); 4,786 (3,679 to 5,836); 13,112 (5,819 to 19,952); and 7,124 (5,053 to 9,212) deaths, respectively. INTERPRETATION: Among major modifiable NCD risk factors, population-level reductions in salt intake and physical inactivity present the greatest opportunity for reducing NCD mortality in Turkey. These findings can help Turkey prioritise interventions to meet the Sustainable Development Goal target of reducing NCD mortality by one third, by 2030.

Cutaneous Chromatophoromas in Four Species of Australian Elapid Snake.

This report documents the clinicopathological features of cutaneous chromatophoromas in four wild-caught, captive Australian elapid snakes: a strap-snouted brown snake (Pseudonaja aspidoryncha), a tiger snake (Notechis scutatus), an Eastern brown snake (Pseudonaja textilis) and a Mengden's brown snake (Pseudonaja mengdeni). All tumours were subclassified as melanophoromas, with three assessed as malignant on the basis of invasive growth or presence of intracoelomic metastases. The chromatophoromas were single or multiple, black or orange pigmented, cutaneous, sometimes ulcerated, plaques or nodules. Microscopically, the neoplastic cells were often spindle shaped with low or variable pigmentation. Neoplastic cells in one tumour were notable for their pleomorphic round cell morphology and high mitotic rate. One snake with late-stage metastasis survived for over 5 years. There are few reports of chromatophoromas in elapid snakes and, to our knowledge, this is the first report of these tumours in Australian elapid snakes.

Implementation of non-communicable disease policies: a geopolitical analysis of 151 countries.

BACKGROUND: Most countries have endorsed WHO non-communicable disease (NCD) best buy policies, but we know very little about global implementation patterns and about the geopolitical factors affecting implementation. We aimed to assess global implementation based on analysis of multiple geopolitical datasets. METHODS: We used the 2015 and 2017 WHO NCD progress monitor reports to calculate aggregate implementation scores for 151 countries, based on their implementation of 18 WHO-recommended NCD policies. We ranked all countries and used descriptive statistics to analyse global trends. We used linear regression to assess the associations between policy implementation and World Bank geographic region, risk of premature NCD mortality, percentage of all deaths caused by NCDs, World Bank income group, human capital index, democracy index, and tax burden. FINDINGS: In 2017, the mean NCD policy implementation score was 49·3% (SD 18·4%). Costa Rica and Iran had the joint-highest implementation scores (86·1% of all WHO-recommended policies). Scores were lowest in Haiti and South Sudan (5·5%). Between 2015 and 2017, aggregate implementation scores rose in 109 countries and regressed in 32 countries. Mean implementation rose for all of the 18 policies except for those targeting alcohol and physical activity. The most commonly implemented policies were clinical guidelines, graphic warnings on tobacco packaging, and NCD risk factor surveys. Our multiple linear regression model explained 61·1% of the variance in 2017 aggregate scores (p<0·0001), but we found evidence of a high degree of collinearity between the explanatory variables. INTERPRETATION: Implementation of WHO-recommended NCD policies is increasing over time. On average, countries implemented just under half of the NCD policies recommended by WHO in 2017. Nutrition-related policies saw gains, while those related to alcohol and physical activity were the most likely to have been dropped. Aggregate implementation scores tended to be highest in high-income countries that invest in health care and education. FUNDING: National Institute for Health Research, Imperial College London, University of Oxford.

A Taxon-Specific and High-Throughput Method for Measuring Ligand Binding to Nicotinic Acetylcholine Receptors.

The binding of compounds to nicotinic acetylcholine receptors is of great interest in biomedical research. However, progress in this area is hampered by the lack of a high-throughput, cost-effective, and taxonomically flexible platform. Current methods are low-throughput, consume large quantities of sample, or are taxonomically limited in which targets can be tested. We describe a novel assay which utilizes a label-free bio-layer interferometry technology, in combination with adapted mimotope peptides, in order to measure ligand binding to the orthosteric site of nicotinic acetylcholine receptor alpha-subunits of diverse organisms. We validated the method by testing the evolutionary patterns of a generalist feeding species (Acanthophis antarcticus), a fish specialist species (Aipysurus laevis), and a snake specialist species (Ophiophagus hannah) for comparative binding to the orthosteric site of fish, amphibian, lizard, snake, bird, marsupial, and rodent alpha-1 nicotinic acetylcholine receptors. Binding patterns corresponded with diet, with the Acanthophis antarcticus not showing bias towards any particular lineage, while Aipysurus laevis showed selectivity for fish, and Ophiophagus hannah a selectivity for snake. To validate the biodiscovery potential of this method, we screened Acanthophis antarcticus and Tropidolaemus wagleri venom for binding to human alpha-1, alpha-2, alpha-3, alpha-4, alpha-5, alpha-6, alpha-7, alpha-9, and alpha-10. While A. antarcticus was broadly potent, T. wagleri showed very strong but selective binding, specifically to the alpha-1 target which would be evolutionarily selected for, as well as the alpha-5 target which is of major interest for drug design and development. Thus, we have shown that our novel method is broadly applicable for studies including evolutionary patterns of venom diversification, predicting potential neurotoxic effects in human envenomed patients, and searches for novel ligands of interest for laboratory tools and in drug design and development.

A systematic review of associations between non-communicable diseases and socioeconomic status within low- and lower-middle-income countries.

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. Eighty-two percent of premature NCD deaths occur within low- and lower middle-income countries (LLMICs). Research to date, largely drawn from high-income countries, suggests that disadvantaged and marginalized groups have a higher NCD burden, but there has been a dearth of research studying this relationship within LLMICs. The purpose of this systematic review is to map the literature on evidence from LLMICs on the socio-economic status (SES) gradient of four particular NCDs: cardiovascular disease, cancer, diabetes, and chronic respiratory diseases. METHODS: We conducted a comprehensive literature search for primary research published between 1 January 1990 and 27 April 2015 using six bibliographic databases and web resources. We included studies that reported SES and morbidity or mortality from cardiovascular disease, cancer, diabetes and chronic respiratory diseases within LLMICs. RESULTS: Fifty-seven studies from 17 LLMICs met our inclusion criteria. Fourteen of the 18 papers that reported significant associations between cancer and SES suggested that low SES groups had the highest cancer risk. Eleven of 15 papers reporting significant relationships between CVD and SES suggested that low SES groups have higher risk. In contrast, seven of 12 papers reporting significant findings related to diabetes found that higher SES groups had higher diabetes risk. We identified just three studies on the relationship between chronic respiratory diseases and SES; none of them reported significant findings. CONCLUSIONS: Only 17 of the 84 LLMICs were represented, highlighting the need for more research on NCDs within these countries. The majority of studies were medium to high quality cross-sectional studies. When we restricted our analyses to high quality studies only, for both cancer and cardiovascular disease more than half of studies found a significantly higher risk for those of lower SES. The opposite was true for diabetes, whilst there was a paucity of high quality research on chronic respiratory disease. Development programmes must consider health alongside other aims and NCD prevention interventions must target all members of the population. SYSTEMATIC REVIEW REGISTRATION NUMBER: Prospero: CRD42015020169.

Evaluation of research on interventions aligned to WHO 'Best Buys' for NCDs in low-income and lower-middle-income countries: a systematic review from 1990 to 2015.

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death and disability worldwide, with low-income and middle-income countries experiencing a disproportionately high burden. Since 2010 WHO has promoted 24 highly cost-effective interventions for NCDs, dubbed 'best buys'. It is unclear whether these interventions have been evaluated in low-income and lower-middle-income countries (LLMICs). AIM: To systematically review research on interventions aligned to WHO 'best buys' for NCDs in LLMICs. METHODS: We searched 13 major databases and included papers conducted in the 83 World Bank-defined LLMICs, published between 1 January 1990 and 5 February 2015. Two reviewers independently screened papers and assessed risk of bias. We adopted a narrative approach to data synthesis. The primary outcomes were NCD-related mortality and morbidity, and risk factor prevalence. RESULTS: We identified 2672 records, of which 36 were included (608 940 participants). No studies on 'best buys' were found in 89% of LLMICs. Nineteen of the 36 studies reported on the effectiveness of tobacco-related 'best buys', presenting good evidence for group interventions in reducing tobacco use but weaker evidence for interventions targeting individuals. There were fewer studies on smoking bans, warning labels and mass media campaigns, and no studies on taxes or marketing restrictions. There was supportive evidence that cervical screening and hepatitis B immunisation prevent cancer in LLMICs. A single randomised controlled trial supported polypharmacy for cardiovascular disease. Fourteen of the 'best buy' interventions did not have any good evidence for effectiveness in LLMICs. CONCLUSIONS: We found studies on only 11 of the 24 interventions aligned with the WHO 'best buys' from LLMIC settings. Most LLMICs have not conducted research on these interventions in their populations. LLMICs should take action to implement and evaluate 'best buys' in their national context, based on national priorities, and starting with interventions with the strongest evidence base.

The impact of poverty reduction and development interventions on non-communicable diseases and their behavioural risk factors in low and lower-middle income countries: A systematic review.

INTRODUCTION: Non-communicable diseases (NCDs) disproportionately affect low- and lower-middle income countries (LLMICs) where 80% of global NCD related deaths occur. LLMICs are the primary focus of interventions to address development and poverty indicators. We aimed to synthesise the evidence of these interventions' impact on the four primary NCDs (cardiovascular disease, diabetes, chronic respiratory disease and cancer) and their common behavioural risk factors (unhealthy diets, physical inactivity, tobacco and alcohol use). METHODS: We systematically searched four online databases (Medline, Embase, Web of Science and Global Health) for primary research conducted in LLMICS, published between January 1st 1990 and February 15th 2016. Studies involved development or poverty interventions which reported on outcomes relating to NCDs. We extracted summary level data on study design, population, health outcomes and potential confounders. RESULTS: From 6383 search results, 29 studies from 24 LLMICs published between 1999 and 2015 met our inclusion criteria. The quality of included studies was limited and heterogeneity of outcome measures required narrative synthesis. One study measured impact on NCD prevalence, one physical activity and 27 dietary components. The majority of papers (23), involved agricultural interventions. Primary outcome measures tended to focus on undernutrition. Intensive agricultural interventions were associated with improved calorie, vitamin, fruit and vegetable intake. However, positive impacts were reliant on participant's land ownership, infection status and limited in generalisability. Just three studies measured adult obesity; two indicated increased income and consequential food affordability had the potential to increase obesity. Overall, there was poor alignment between included studies outcome measures and the key policy options and objectives of the Global Action Plan on NCDs. CONCLUSIONS: Though many interventions addressing poverty and development have great potential to impact on NCD prevalence and risk, most fail to measure or report these outcomes. Current evidence is limited to behavioural risk factors, namely diet and suggests a positive impact of agricultural-based food security programmes on dietary indicators. However, studies investigating the impact of improved income on obesity tend to show an increased risk. Embedding NCD impact evaluation into development programmes is crucial in the context of the Sustainable Development Goals and the rapid epidemiological transitions facing LLMICs.