Adaptive Health Technology Assessment: A Scoping Review of Methods.

OBJECTIVES: Health technology assessment (HTA) is an established mechanism for explicit priority setting to support universal health coverage. However, full HTA requires significant time, data, and capacity for each intervention, which limits the number of decisions it can inform. Another approach systematically adapts full HTA methods by leveraging HTA evidence from other settings. We call this "adaptive" HTA (aHTA), although in settings where time is the main constraint, it is also called "rapid HTA." METHODS: The objectives of this scoping review were to identify and map existing aHTA methods, and to assess their triggers, strengths, and weaknesses. This was done by searching HTA agencies' and networks' websites, and the published literature. Findings have been narratively synthesized. RESULTS: This review identified 20 countries and 1 HTA network with aHTA methods in the Americas, Europe, Africa, and South-East Asia. These methods have been characterized into 5 types: rapid reviews, rapid cost-effectiveness analyses, rapid manufacturer submissions, transfers, and de facto HTA. Three characteristics "trigger" the use of aHTA instead of full HTA: urgency, certainty, and low budget impact. Sometimes, an iterative approach to selecting methods guides whether to do aHTA or full HTA. aHTA was found to be faster and more efficient, useful for decision makers, and to reduce duplication. Nevertheless, there is limited standardization, transparency, and measurement of uncertainty. CONCLUSIONS: aHTA is used in many settings. It has potential to improve the efficiency of any priority-setting system, but needs to be better formalized to improve uptake, particularly for nascent HTA systems.

Earthquake exposure, adverse childhood experiences, and psychosocial functioning in Chilean children: A longitudinal study.

The impact of an 8.8 magnitude Chilean earthquake on elementary school students' psychosocial functioning was assessed along with exposure to adverse childhood experiences (ACEs). Skills for Life, a national school-based mental health program in Chile, routinely assesses first- and third-grade students' psychosocial functioning and classroom adaptation. Students (N = 19,627) were screened before (2009) and after (2011) the 2010 earthquake with parent- and teacher-report measures and with a parent-report of four ACEs (family psychopathology, child chronic illness, family social isolation, father absence). Earthquake exposure was categorized as mild, moderate, or severe for Chile's 15 regions. Multilevel models analyzed the unadjusted and adjusted impacts of earthquake exposure and ACEs on functioning while clustering for school- and district-level effects. In covariate-adjusted models, earthquake exposure and three ACEs were significantly associated with worsened psychosocial functioning; earthquake exposure and all four ACEs were significantly associated with worsened classroom adaptation. New family psychopathology, B = 1.90, p < .001; chronic illness, B = 2.25, p < .001; and severe earthquake impact, B = 1.29, p < .001, held the strongest negative effects on psychosocial well-being. Moderate, B = 3.04, p = .011, and severe earthquake exposure, B = 2.53, p = .047, and new family psychopathology, B = 1.99, p < .001, were associated with the worst classroom functioning 1-year postdisaster. Findings suggest that both exogenous and home-based stressors can have significant consequences for children's psychosocial functioning and classroom adaptation, and routine screening helps quantify how individual students are affected by chronic versus acute stressors.

Human health risk of methylmercury from fish consumption at the largest floodplain in Colombia.

Colombia is one of the countries with the highest emissions of mercury (Hg) to the environment, due to its use in gold mining. This study evaluated the human health risk from exposure to Hg through fish consumption in 11 municipalities located in the Mojana region, northern Colombia. The study participants (n = 839) were categorized into three population groups: children (CHD), women of childbearing age (WCHA) and the rest of population (RP). Total Hg (THg) and methylmercury (MeHg) concentrations were evaluated in the top ten most consumed fish species (n = 292). Median concentrations (range: 0.22-0.58 µg/g ww) of the five carnivorous fish species exceeded the reference limit established by FAO/WHO (0.2 µg/g ww) for vulnerable populations. For 6 of the 10 studied fish species, the estimated weekly intake (EWI) in children was above the provisional tolerable weekly intake (PTWI, 1.6 µg/kg bw/week) of MeHg established by JECFA. EWI values for WCHA were above PTWI in 4 fish species, whereas in general, for RP group values were below PTWI (3.2 µg/kg bw/week). Our assessment of potential risks to MeHg exposure indicated that most of the consumed fish could generate negative effects in vulnerable groups, because according to ingestion rate, MeHg permissible is, in some cases, up to 4 times higher than reference limits. Consumption advisories should be a guidance to avoid risk, gain nutritional benefits, and sustain fish populations. Because its high MeHg levels as well as high ingestion, it is recommended that inhabitants of this region should stop eating certain kinds of fish and the whole fish as a single meal. To reduce its harmful intake, we have proposed a didactic strategy based on marbles that control the portion of fish they are eating.

A before-school physical activity intervention to improve cognitive parameters in children: The Active-Start study.

The aim of the study was threefold: (a) to test a before-school physical activity intervention (Active-Start) on academic performance, selective attention, and concentration capacity; (b) to test the effect of the Active-Start intervention on anthropometry, body composition, and physical fitness parameters; and (c) whether the physical fitness components are moderators of the effect of the Active-Start program on academic performance, selective attention, and concentration capacity in Chilean children. The Active-Start intervention was a RCT which comprised 170 children (8-10 years old) from three public schools with low socioeconomic status from the city of Santiago (Chile). The exercise intervention was delivered daily, before starting the first school-class (8:00-8:30 am) for 8 weeks. Changes in academic performance, selective attention and concentration capacity, anthropometric, body composition, and physical fitness parameters were measured. The analyses used were mixed regression models for repeated measures over time. No statistically significant changes in attention and concentration capacity were found. However, significant changes were seen in language (0.63; 95% CI 0.49-0.77) and mathematics (0.49; 95% CI 0.32-0.66) performance (P < .001). Also, improvements were seen in fat mass, fat-free mass, muscular, and cardiorespiratory fitness (all P < .05). The Johnson-Neyman technique revealed a significant relationship between the effect of intervention and attention and concentration when change in cardiorespiratory fitness was above, but not below, 3.05 and 0.70 mL/kg/min, respectively. Implementing before-school physical activity programs such as the Active-Start to enhance the cardiorespiratory fitness may benefit attention capacity and academic success among schoolchildren.

Simultaneous Estimation of Vehicle Roll and Sideslip Angles through a Deep Learning Approach.

Presently, autonomous vehicles are on the rise and are expected to be on the roads in the coming years. In this sense, it becomes necessary to have adequate knowledge about its states to design controllers capable of providing adequate performance in all driving scenarios. Sideslip and roll angles are critical parameters in vehicular lateral stability. The later has a high impact on vehicles with an elevated center of gravity, such as trucks, buses, and industrial vehicles, among others, as they are prone to rollover. Due to the high cost of the current sensors used to measure these angles directly, much of the research is focused on estimating them. One of the drawbacks is that vehicles are strong non-linear systems that require specific methods able to tackle this feature. The evolution in Artificial Intelligence models, such as the complex Artificial Neural Network architectures that compose the Deep Learning paradigm, has shown to provide excellent performance for complex and non-linear control problems. In this paper, the authors propose an inexpensive but powerful model based on Deep Learning to estimate the roll and sideslip angles simultaneously in mass production vehicles. The model uses input signals which can be obtained directly from onboard vehicle sensors such as the longitudinal and lateral accelerations, steering angle and roll and yaw rates. The model was trained using hundreds of thousands of data provided by Trucksim® and validated using data captured from real driving maneuvers using a calibrated ground truth device such as VBOX3i dual-antenna GPS from Racelogic®. The use of both Trucksim® software and the VBOX measuring equipment is recognized and widely used in the automotive sector, providing robust data for the research shown in this article.

Epidemiology of Achilles tendon injuries in collegiate level athletes in the United States.

BACKGROUND: Achilles injuries are devastating injuries, especially for competitive athletes. No studies have examined the outcomes of Achilles injuries in NCAA athletes. Therefore, a better characterization and understanding of the epidemiology is crucial. METHODS: Achilles injuries across 16 sports among NCAA men and women during the 2004-2005 to 2013-2014 academic years were analyzed using the NCAA Injury Surveillance Program (NCAA-ISP). Achilles tendon injury rate (IR) per 100,000 athlete-exposures (AEs), operative rate, annual injury rate trends, reinjury rates, mechanism of injury, in-season status (pre/regular/post season), and time loss distributions were compiled and calculated. A sub-analysis of comparing gender and injury mechanism was also performed for both all injuries and severe injuries. RESULTS: Overall, N = 255 Achilles injuries were identified with an injury rate (IR) of 2.17 (per 100,000 AEs). These injuries occurred most often in women's gymnastics (IR = 16.73), men's basketball (IR = 4.26), and women's basketball (IR = 3.32), respectively. N = 52 injuries were classified as severe injuries which have higher median time loss (48 days) and higher operative rate (65.4%). For severe Achilles injuries, female athletes had higher operative (77.8% vs. 58.8%) and higher time loss compared to male athletes (96 days vs. 48 days). Contact mechanisms were associated with a higher season-ending injury rate. CONCLUSION: Overall, 20.4% of Achilles injuries were considered severe with 65.6% operative rate. About 73.1% were season-ending injuries, and the remaining athletes have a median time loss of 48 days. Severe Achilles injuries create significant impact on playing time and career for NCAA athletes.

Percutaneous Zadek osteotomy for the treatment of insertional Achilles tendinopathy.

BACKGROUND: Insertional Achilles tendinopathy (IAT) is a challenging common lower extremity disorder, despite several treatment options described in literature. Open dorsal closing wedge calcaneal osteotomy or Zadek Osteotomy (ZO), for the treatment of the IAT has good clinical results but a high rate of postoperative complications. The purpose of this study is to describe percutaneous ZO for the treatment of the IAT and to evaluate its impact on the clinical and functional postoperative outcomes. METHODS: Twenty-six consecutive patients presenting with unilateral IAT refractory to nonoperative measures were treated with percutaneous ZO. Visual Analogue Scale (VAS) and Foot Function Index Score (FFI) were recorded preoperatively and at final follow-up visit (12±3) months. Postoperative complications, satisfaction, and relief of the pain were also recorded. RESULTS: The percutaneous ZO showed a significant improvement (p<0.0001) in preoperative to postoperative FFI (from 65±9 to 8±12) and VAS (from 9±1 to 1±2). Two postoperative complications (8%) were observed: a case of symptomatic non-union and hardware pain, both in healthy patients. The overall rate of satisfaction after surgery was (92%). The relief from pain was achieved after an average period of 12 weeks. CONCLUSIONS: ZO is a safe and effective procedure for the treatment of IAT. The use of a minimally invasive surgical approach is associated with excellent pain reduction (VAS score) and improved clinical function (FFI score). When compared to the open surgical approach, the percutaneous ZO may decrease recovery time and postoperative complications. LEVEL OF EVIDENCE: III, retrospective case series.

New Paradigms in the Continuum of Spine Care: From Newborns to Elderly Patients.

The evaluation and management of spinal disorders is complex and constantly evolving. Back pain and spinal deformity are substantial contributors to hospital and outpatient physician visits even for young patients. With new insights into the etiology, clinical presentation, and evaluation, children can be more accurately diagnosed and treated. Patients with adolescent idiopathic scoliosis may undergo selective fusion to preserve motion segments, and in some cases, vertebral body tethering or other growth-modification techniques may provide correction with motion preservation in this rapidly changing specialty. The understanding of spinopelvic parameters (pelvic incidence, pelvic tilt, sacral slope) and sagittal balance as they relate to clinical health status has provided surgeons with valuable guidance when managing pediatric and adult spinal deformity. An evidence-based approach to the management of spinal disorders across the continuum of ages has the goal of improving the value of care through optimization of outcomes and limitation of costs and complications. There are new paradigms in the management of spinal disorders and evidence-based approaches to the evaluation and management of patients across the ages.

Biomagnification of Mercury in Fish from Two Gold Mining-Impacted Tropical Marshes in Northern Colombia.

Total mercury concentrations (T-Hg) and stable isotope ratios (δ15N and δ13C) were analyzed in the muscle of fish, collected at two marshes impacted by gold mining in Northern Colombia, to evaluate the seasonal and spatial behavior of these variables and mercury biomagnification based on their relationship with δ15N ratios in the fish. There was not significant (p > 0.05) seasonal differences (dry and rainy season) in δ15N and δ13C values in none marsh, suggesting that these fish species keep a similar feed pattern within each marsh along the year. However, there were significant differences (p < 0.05) between marshes in δ15N, δ13C, and T-Hg, as well as significant seasonal differences (p < 0.05) in T-Hg values for some species, suggesting the possible influence of factors, such as differences in length of food chains between marshes and different degree of anthropogenic impact in relation to human settlements, farmland, livestock (higher in Ayapel marsh), and gold mining activity (higher in La Raya marsh). Correlations analysis showed significant (p < 0.05) relationships between T-Hg concentrations and δ15N values, as well as trophic level, evidencing a T-Hg biomagnification process in the fish food chain from both marshes and consequently a potential health risk for human riverside inhabitants who eat these fish.

VEHIOT: Design and Evaluation of an IoT Architecture Based on Low-Cost Devices to Be Embedded in Production Vehicles.

Nowadays, the current vehicles are incorporating control systems in order to improve their stability and handling. These control systems need to know the vehicle dynamics through the variables (lateral acceleration, roll rate, roll angle, sideslip angle, etc.) that are obtained or estimated from sensors. For this goal, it is necessary to mount on vehicles not only low-cost sensors, but also low-cost embedded systems, which allow acquiring data from sensors and executing the developed algorithms to estimate and to control with novel higher speed computing. All these devices have to be integrated in an adequate architecture with enough performance in terms of accuracy, reliability and processing time. In this article, an architecture to carry out the estimation and control of vehicle dynamics has been developed. This architecture was designed considering the basic principles of IoT and integrates low-cost sensors and embedded hardware for orchestrating the experiments. A comparison of two different low-cost systems in terms of accuracy, acquisition time and reliability has been done. Both devices have been compared with the VBOX device from Racelogic, which has been used as the ground truth. The comparison has been made from tests carried out in a real vehicle. The lateral acceleration and roll rate have been analyzed in order to quantify the error of these devices.

Design of Low-Cost Vehicle Roll Angle Estimator Based on Kalman Filters and an Iot Architecture.

In recent years, there have been many advances in vehicle technologies based on the efficient use of real-time data provided by embedded sensors. Some of these technologies can help you avoid or reduce the severity of a crash such as the Roll Stability Control (RSC) systems for commercial vehicles. In RSC, several critical variables to consider such as sideslip or roll angle can only be directly measured using expensive equipment. These kind of devices would increase the price of commercial vehicles. Nevertheless, sideslip or roll angle or values can be estimated using MEMS sensors in combination with data fusion algorithms. The objectives stated for this research work consist of integrating roll angle estimators based on Linear and Unscented Kalman filters to evaluate the precision of the results obtained and determining the fulfillment of the hard real-time processing constraints to embed this kind of estimators in IoT architectures based on low-cost equipment able to be deployed in commercial vehicles. An experimental testbed composed of a van with two sets of low-cost kits was set up, the first one including a Raspberry Pi 3 Model B, and the other having an Intel Edison System on Chip. This experimental environment was tested under different conditions for comparison. The results obtained from low-cost experimental kits, based on IoT architectures and including estimators based on Kalman filters, provide accurate roll angle estimation. Also, these results show that the processing time to get the data and execute the estimations based on Kalman Filters fulfill hard real time constraints.

Real-Time Vehicle Roll Angle Estimation Based on Neural Networks in IoT Low-Cost Devices.

The high rate of vehicle-crash victims has a fatal economic and social impact in today’s societies. In particular, road crashes where heavy vehicles are involved cause more severe damage because they are prone to rollover. For this reason, many researches are focused on developing RSC Roll Stability Control (RSC) systems. Concerning the design of RSC systems with an adequate performance, it is mandatory to know the dynamics of the vehicle. The main problem arises from the lack of ability to directly capture several required dynamic vehicle variables, such as roll angle, from low-cost sensors. Previous studies demonstrate that low-cost sensors can provide data in real-time with the required precision and reliability. Even more, other research works indicate that neural networks are efficient mechanisms to estimate roll angle. Nevertheless, it is necessary to assess that the fusion of data coming from low-cost devices and estimations provided by neural networks can fulfill hard real-time processing constraints, achieving high level of accuracy during circulation of a vehicle in real situations. In order to address this issue, this study has two main goals: (1) Design and develop an IoT based architecture, integrating ANN in low cost kits with different hardware architectures in order to estimate under real-time constraints the vehicle roll angle. This architecture is able to work under high dynamic conditions, by following specific best practices and considerations during its design; (2) assess that the IoT architecture deployed in low-cost experimental kits achieve the hard real-time performance constraints estimating the roll angle with the required calculation accuracy. To fulfil these objectives, an experimental environment was set up, composed of a van with two set of low-cost kits, one including a Raspberry Pi 3 Model Band the other having an Intel Edison System on Chip linked to a SparkFun 9 Degrees of Freedom module. This experimental environment be tested in different maneuvers for comparison purposes. Neural networks embedded in low-cost sensor kits provide roll angle estimations highly approximated to real values. Even more, Intel Edison and Raspberry Pi 3 Model B have enough computing capabilities to successfully run roll angle estimation based on neural networks to determine rollover risk situations, fulfilling real-time operation restrictions stated for this problem.

[Exercise and oxidative stress in type 2 diabetes mellitus]. / Efecto del ejercicio físico sobre marcadores de estrés oxidativo en pacientes con diabetes mellitus tipo 2.

Sedentarism, overweight and malnutrition generate an increase in the production of reactive oxygen species leading to a state of chronic oxidative stress. In patients with type 2 diabetes mellitus, oxidative stress alters pancreatic insulin secretion and the actions of the hormone on target cells, contributing to the development of micro and macrovascular complications. During physical exertion a state of transient oxidative stress occurs. As a consequence, the organism generates multiple physiological adaptations to these repetitive stimuli. Physical exercise is beneficial for type 2 diabetes mellitus but there is a paucity of information about the effects of physical exercise on biomarkers of oxidative stress in patients with the disease. We herein try to elucidate if the effects of exercise on oxidative stress can help in the prevention and treatment of type 2 diabetes mellitus and which is the most effective modality of physical exercise to reduce oxidative stress markers.

[Model for a risk-focused approach to health inspection, surveillance, and control in Colombia]. / Modelo para la inspección, vigilancia y control sanitario con enfoque de riesgos en Colombia.

Colombian Ministry of Health Resolution 1229 of 2013 established that health inspection, surveillance, and control (IVC, Spanish acronym) should be based on a risk-focused approach. In 2014 Colombia´s National Food and Drugs Surveillance Institute (INVIMA) designed and implemented a risk-based health surveillance model called IVC-SOA. This model measures the risks of drugs, medical devices, food, and cosmetics by taking into account three factors: severity of the product (S), occurrence of product failure (O), and the potentially affected population (A) - hence its name, SOA. The model incorporates 40 variables and statistical methods that make it possible to create a risk profile for each entity surveyed, and thus to generate a ranking to determine which should be inspected. The objective of this report is to describe the methodology and results obtained following the design and implementation of the IVC-SOA model created by the regulatory agency in Colombia, and its impact on health surveillance effectiveness.

[Use of Leersia hexandra (Poaceae) for soil phytoremediation in soils contaminated with fresh and weathered oil]. / Uso de Leersia hecandra (Poaceae) en la fitorremediación de suelos contaminados con petróleo fresco e intemperizado.

The oil industry has generated chronic oil spills and their accumulation in wetlands of the state of Tabasco, in Southeastern Mexico. Waterlogging is a factor that limits the use of remediation technologies because of its high cost and low levels of oil degradation. However, Leersia hexandra is a grass that grows in these contaminated areas with weathered oil. The aim of the study was to evaluate the bacteria density, plant biomass production and phytoremediation of L. hexandra in contaminated soil. For this, two experiments in plastic tunnel were performed with fresh (E1) and weathered petroleum (E2) under waterlogging experimental conditions. The E1 was based on eight doses: 6 000, 10 000, 30 000, 60 000, 90 000, 120 000, 150 000 and 180 000 mg.kg-1 dry basis (d. b.) of total petroleum hydrocarbons fresh (TPH-F), and the E2, that evaluated five doses: 14 173, 28 400, 50 598, 75 492 and 112 142 mg. kg-1 d. b. of total petroleum hydrocarbons weathered (TPH-W); a control treatment with 2 607 mg.kg-1 d. b. was used. Each experiment, with eight replicates per treatment, evaluated after three and six months: a) microbial density of total free-living nitrogen-fixing bacteria (NFB) of Azospirillum (AZP) and Azotobacter group (AZT), for viable count in serial plate; b) dry matter production (DMP), quantified gravimetrically as dry weight of L. hexandra; and c) the decontamination percentage of hydrocarbons (PDH) by Soxhlet extraction. In soil with TPH-F, the NFB, AZP y AZT populations were stimulated five times more than the control both at the three and six months; however, concentrations of 150 000 and 180 000 mg.kg-1 d. b. inhibited the bacterial density between 70 and 89 %. Likewise, in soil with TPH-W, the FNB, AZP and AZT inhibitions were 90 %, with the exception of the 14 173 mg.kg-1 d. b. treatment, which stimulated the NFB and AZT in 2 and 0.10 times more than the control, respectively. The DMP was continued at the six months in the experiments, with values of 63 and 89 g in fresh and weathered petroleum, respectively; had no significant differences with the control (p≤0.05). The PDH reached values of 66 to 87 % both TPH-F and TPH-W at six months, respectively. These results demonstrated the ability the L. hexandra rhizosphere to stimulate the high NFB density, vegetal biomass production and phytoremediation of contaminated soils (with fresh and weathered petroleum), in a tropical waterlogging environment.

Reversible Transformation of Pt Nanoparticles into Single Atoms inside High-Silica Chabazite Zeolite.

We report the encapsulation of platinum species in highly siliceous chabazite (CHA) crystallized in the presence of N,N,N-trimethyl-1-adamantammonium and a thiol-stabilized Pt complex. When compared to Pt/SiO2 or Pt-containing Al-rich zeolites, the materials in this work show enhanced stability toward metal sintering in a variety of industrial conditions, including H2, O2, and H2O. Remarkably, temperatures in the range 650-750 °C can be reached without significant sintering of the noble metal. Detailed structural determinations by X-ray absorption spectroscopy and aberration-corrected high-angle annular dark-field scanning transmission electron microscopy demonstrate subtle control of the supported metal structures from ∼1 nm nanoparticles to site-isolated single Pt atoms via reversible interconversion of one species into another in reducing and oxidizing atmospheres. The combined used of microscopy and spectroscopy is critical to understand these surface-mediated transformations. When tested in hydrogenation reactions, Pt/CHA converts ethylene (∼80%) but not propylene under identical conditions, in contrast to Pt/SiO2, which converts both at similar rates. These differences are attributed to the negligible diffusivity of propylene through the small-pore zeolite and provide final evidence of the metal encapsulation.

[Proposed model for managing drugs used for unregistered indications in Colombia]. / Propuesta de un modelo de gestión de medicamentos en indicaciones no registradas en Colombia.

The use of drugs for unregistered indications, known as "off-label" use, is a practice that creates problems of rational use and access when other options are not available. Health systems should address this situation, particularly in connection with decisions concerning coverage, while trying to minimize health risks and clearly define the roles and responsibilities of the parties involved. Colombia's Ministry of Health and Social Protection (MinSalud), together with the National University of Colombia and national experts, developed a proposal for a model for managing drugs being used for unregistered indications (off-label) and their potential reimbursement with public resources, taking into account international practices and country characteristics. The management model is non-punitive and is geared toward promoting the rational use of these drugs so that barriers to access are reduced whenever their use is supported by solid scientific evidence. The model addresses patient safeguards in the bioethical domain and the roles and responsibilities of the prescriber and government entities.

Mental health predicts better academic outcomes: a longitudinal study of elementary school students in Chile.

The world's largest school-based mental health program, Habilidades para la Vida [Skills for Life (SFL)], has been operating on a national scale in Chile for 15 years. SFL's activities include using standardized measures to screen elementary school students and providing preventive workshops to students at risk for mental health problems. This paper used SFL's data on 37,397 students who were in first grade in 2009 and third grade in 2011 to ascertain whether first grade mental health predicted subsequent academic achievement and whether remission of mental health problems predicted improved academic outcomes. Results showed that mental health was a significant predictor of future academic performance and that, overall, students whose mental health improved between first and third grade made better academic progress than students whose mental health did not improve or worsened. Our findings suggest that school-based mental health programs like SFL may help improve students' academic outcomes.

Mapping of available health research and development data: what's there, what's missing, and what role is there for a global observatory?

The need to align investments in health research and development (R&D) with public health demands is one of the most pressing global public health challenges. We aim to provide a comprehensive description of available data sources, propose a set of indicators for monitoring the global landscape of health R&D, and present a sample of country indicators on research inputs (investments), processes (clinical trials), and outputs (publications), based on data from international databases. Total global investments in health R&D (both public and private sector) in 2009 reached US$240 billion. Of the US$214 billion invested in high-income countries, 60% of health R&D investments came from the business sector, 30% from the public sector, and about 10% from other sources (including private non-profit organisations). Only about 1% of all health R&D investments were allocated to neglected diseases in 2010. Diseases of relevance to high-income countries were investigated in clinical trials seven-to-eight-times more often than were diseases whose burden lies mainly in low-income and middle-income countries. This report confirms that substantial gaps in the global landscape of health R&D remain, especially for and in low-income and middle-income countries. Too few investments are targeted towards the health needs of these countries. Better data are needed to improve priority setting and coordination for health R&D, ultimately to ensure that resources are allocated to diseases and regions where they are needed the most. The establishment of a global observatory on health R&D, which is being discussed at WHO, could address the absence of a comprehensive and sustainable mechanism for regular global monitoring of health R&D.