The development and implementation of an oxygen treatment solution for health facilities in low and middle-income countries.

BACKGROUND: Oxygen reduces mortality from severe pneumonia and is a vital part of case management, but achieving reliable access to oxygen is challenging in low and middle-income country (LMIC) settings. We developed and field tested two oxygen supply solutions suitable for the realities of LMIC health facilities. METHODS: A Health Needs Assessment identified a technology gap preventing reliable oxygen supplies in Gambian hospitals. We used simultaneous engineering to develop two solutions: a Mains-Power Storage (Mains-PS) system consisting of an oxygen concentrator and batteries connected to mains power, and a Solar-Power Storage (Solar-PS) system (with batteries charged by photovoltaic panels) and evaluated them in health facilities in The Gambia and Fiji to assess reliability, usability and costs. RESULTS: The Mains-PS system delivered the specified ≥85% (±3%) oxygen concentration in 100% of 1-2 weekly measurements over 12 months, which was available to 100% of hypoxaemic patients, and 100% of users rated ease-of-use as at least 'good' (90% very good or excellent). The Solar-PS system delivered ≥85% ± 3%) oxygen concentration in 100% of 1-2 weekly measurements, was available to 100% of patients needing oxygen, and 100% of users rated ease-of-use at least very good.Costs for the systems (in US dollars) were: PS$9519, Solar-PS standard version $20 718. The of oxygen for a standardised 30-bed health facility using 1.7 million litres of oxygen per year was: for cylinders 3.2 cents (c)/L in The Gambia and 6.8 c/L in Fiji, for the PS system 1.2 c/L in both countries, and for the Solar-PS system 1.5 c/L in both countries. CONCLUSIONS: The oxygen systems developed and tested delivered high-quality, reliable, cost-efficient oxygen in LMIC contexts, and were easy to operate. Reliable oxygen supplies are achievable in LMIC health facilities like those in The Gambia and Fiji.

A framework for the management of donated medical devices based on perspectives of frontline public health care staff in Ghana.

Background: Transnational funders provide up to 80% of funds for medical devices in resource-limited settings, yet sustained access to medical devices remains unachievable. The primary goal of this study was to identify what factors hinder access to medical devices through the perspectives of frontline public hospital staff in Ghana involved in the implementation of transnational funding initiatives. Methods: A case study was developed that involved an analysis of semi-structured interviews of 57 frontline technical, clinical and administrative public health care staff at 23 sites in Ghana between March and April 2017; a review of the national guidelines for donations; and images of abandoned medical devices. Results: Six key themes emerged, demonstrating how policy, collaboration, quality, lifetime operating costs, attitudes of health care workers and representational leadership influence access to medical devices. An in-depth assessment of these themes has led to the development of an enterprise-wide comprehensive acquisition and management framework for medical devices in the context of transnational funding initiatives. Conclusion: The findings in this study underscore the importance of incorporating frontline health care staff in developing solutions that are targeted at improving delivery of care. Sustained access to medical devices may be achieved in Ghana through the adoption of a rigorous and comprehensive approach to acquisition, management and technical leadership. Funders and public health policy makers may use the study's findings to inform policy reform and to ensure that the efforts of transnational funders truly help to facilitate sustainable access to medical devices in Ghana.

Cost comparison of centralized and decentralized wastewater management systems using optimization model.

There is a growing interest in decentralized wastewater management (DWWM) as a potential alternative to centralized wastewater management (CWWM) in developing countries. However, the comparative cost of CWWM and DWWM is not well understood. In this study, the cost of cluster-type DWWM is simulated and compared to the cost of CWWM in Alibag, India. A three-step model is built to simulate a broad range of potential DWWM configurations with varying number and layout of cluster subsystems. The considered DWWM scheme consists of cluster subsystems, that each uses simplified sewer and DEWATS (Decentralized Wastewater Treatment Systems). We consider CWWM that uses conventional sewer and an activated sludge plant. The results show that the cost of DWWM can vary significantly with the number and layout of the comprising cluster subsystems. The cost of DWWM increased nonlinearly with increasing number of comprising clusters, mainly due to the loss in the economies of scale for DEWATS. For configurations with the same number of comprising cluster subsystems, the cost of DWWM varied by ±5% around the mean, depending on the layout of the cluster subsystems. In comparison to CWWM, DWWM was of lower cost than CWWM when configured with fewer than 16 clusters in Alibag, with significantly less operation and maintenance requirement, but with higher capital and land requirement for construction. The study demonstrates that cluster-type DWWM using simplified sewer and DEWATS may be a cost-competitive alternative to CWWM, when carefully configured to lower the cost.

Exposure-response relationship of neighbourhood sanitation and children's diarrhoea.

OBJECTIVES: To assess the association of neighbourhood sanitation coverage with under-five children's diarrhoeal morbidity and to evaluate its exposure-response relationship. METHODS: We used the Demographic and Health Surveys (DHS) of 29 developing countries in sub-Saharan Africa and South Asia, conducted between 2010 and 2014. The primary outcome was two-week incidence of diarrhoea in children under 5 years of age (N = 269014). We conducted three-level logistic regression analyses and applied cubic splines to assess the trend between neighbourhood-level coverage of improved household sanitation and diarrhoeal morbidity. RESULTS: A significant association between neighbourhood-level coverage of improved household sanitation and diarrhoeal morbidity (OR [95% CI] = 0.68 [0.62-0.76]) was found. Exposure-relationship analyses results showed improved sanitation coverage threshold at 0.6. We found marginal degree of association (OR [95% CI] = 0.82 [0.77-0.87]) below the threshold, which, beyond the threshold, sharply increased to OR of 0.44 (95% CI: 0.29-0.67) at sanitation coverage of 1 (i.e. neighbourhood-wide use of improved household sanitation). Similar exposure-response trends were identified for urban and rural subgroups. CONCLUSIONS: Our findings suggest that neighbourhood sanitation plays a key role in reducing diarrhoeal diseases and that increase in sanitation coverage may only have minimal impact on diarrhoeal illness, unless sufficiently high coverage is achieved.

Operations research in global health: a scoping review with a focus on the themes of health equity and impact.

BACKGROUND: Operations research (OR) is a discipline that uses advanced analytical methods (e.g. simulation, optimisation, decision analysis) to better understand complex systems and aid in decision-making. Herein, we present a scoping review of the use of OR to analyse issues in global health, with an emphasis on health equity and research impact. A systematic search of five databases was designed to identify relevant published literature. A global overview of 1099 studies highlights the geographic distribution of OR and common OR methods used. From this collection of literature, a narrative description of the use of OR across four main application areas of global health - health systems and operations, clinical medicine, public health and health innovation - is also presented. The theme of health equity is then explored in detail through a subset of 44 studies. Health equity is a critical element of global health that cuts across all four application areas, and is an issue particularly amenable to analysis through OR. Finally, we present seven select cases of OR analyses that have been implemented or have influenced decision-making in global health policy or practice. Based on these cases, we identify three key drivers for success in bridging the gap between OR and global health policy, namely international collaboration with stakeholders, use of contextually appropriate data, and varied communication outlets for research findings. Such cases, however, represent a very small proportion of the literature found. CONCLUSION: Poor availability of representative and quality data, and a lack of collaboration between those who develop OR models and stakeholders in the contexts where OR analyses are intended to serve, were found to be common challenges for effective OR modelling in global health.

Effects of neighbourhood and household sanitation conditions on diarrhea morbidity: Systematic review and meta-analysis.

Sanitation in neighbourhood and household domains can provide primary protection against diarrhea morbidity, yet their distinct health benefits have not been succinctly distinguished and reviewed. We present here the first systematic review and meta-analysis of the distinct effect of neighbourhood and household sanitation conditions on diarrhea morbidity. We identified studies reporting the effect of neighbourhood-level exposure to wastewater or household sanitation facilities on diarrhea, by performing comprehensive search on five databases, namely the Cochrane library, PubMed, Embase, Scopus and Web of Science, from the earliest date available to February 2015. Twenty-one non-randomized studies and one randomized controlled trial met the pre-determined inclusion criteria, consisting of six datasets on neighbourhood sanitation conditions (total 8271 subjects) and 20 datasets on household sanitation (total 20021 subjects). We calculated the pooled effect estimates of neighbourhood and household sanitation conditions on diarrhea morbidity using the inverse variance random-effects model. The pooled effect estimates showed that both neighbourhood sanitation conditions (odds ratio = 0.56, 95%CI: 0.40-0.79) and household sanitation (odds ratio = 0.64, 95%CI: 0.55-0.75) are associated with reduced diarrheal illness, and that the magnitudes of the associations are comparable. Evidence of risk of bias and heterogeneity were found in the included studies. Our findings confirm that both neighbourhood sanitation conditions and household sanitation are associated with considerable reduction in diarrhea morbidity, in spite of a number of methodological shortcomings in the included studies. Furthermore, we find evidence that neighbourhood sanitation conditions is associated with similar magnitude of reduction in diarrhea morbidity as household sanitation. The findings suggest that, in addition to household sanitation provision, dual emphasis on neighbourhood sanitation through public sanitation infrastructure provision and community-wide sanitation adoption is advisable for effective reduction of diarrheal disease burden.

Continuous, self-sustaining smouldering destruction of simulated faeces.

A new approach for the rapid destruction of human waste using smouldering combustion is presented. Recently, self-sustaining smouldering combustion was shown to destroy the organic component of simulated human solid waste and dog faeces resulting in the sanitization of all pathogens using a batch process (Yermán et al., 2015). Here, a continuous smouldering process is demonstrated for the first time, allowing for a much smaller reactor size and much less energy input per mass of waste treated. The self-sustained smouldering of simulated human faeces mixed with sand is evaluated over long periods (more than 16 h) based on a single ignition. The key process of intermittent self-sustained smouldering, in which the reaction is terminated and restarted by only turning the air off and on, is demonstrated. Experiments examine the influence of two key operator controls: airflow rate and set elevation of the quasi-steady-state smouldering front in a 37 cm high reactor. Quasi-steady-state fuel destruction rates from 93 g/h to 12 g/h were achieved by varying the superficial flow velocity from 7.4 cm/s to 0.11 cm/s, the latter with a velocity approximately an order of magnitude lower than possible for a self-sustaining reaction in an equivalent batch system. Excess energy of up to 140 J/g of sand was recovered from the clean sand produced in each cycle, which could be used to further increase the energy efficiency of this novel waste treatment system.

Criteria to assess potential reverse innovations: opportunities for shared learning between high- and low-income countries.

BACKGROUND: Low- and middle-income countries (LMICs) are developing novel approaches to healthcare that may be relevant to high-income countries (HICs). These include products, services, organizational processes, or policies that improve access, cost, or efficiency of healthcare. However, given the challenge of replication, it is difficult to identify innovations that could be successfully adapted to high-income settings. We present a set of criteria for evaluating the potential impact of LMIC innovations in HIC settings. METHODS: An initial framework was drafted based on a literature review, and revised iteratively by applying it to LMIC examples from the Center for Health Market Innovations (CHMI) program database. The resulting criteria were then reviewed using a modified Delphi process by the Reverse Innovation Working Group, consisting of 31 experts in medicine, engineering, management and political science, as well as representatives from industry and government, all with an expressed interest in reverse innovation. RESULTS: The resulting 8 criteria are divided into two steps with a simple scoring system. First, innovations are assessed according to their success within the LMIC context according to metrics of improving accessibility, cost-effectiveness, scalability, and overall effectiveness. Next, they are scored for their potential for spread to HICs, according to their ability to address an HIC healthcare challenge, compatibility with infrastructure and regulatory requirements, degree of novelty, and degree of current collaboration with HICs. We use examples to illustrate where programs which appear initially promising may be unlikely to succeed in a HIC setting due to feasibility concerns. CONCLUSIONS: This study presents a framework for identifying reverse innovations that may be useful to policymakers and funding agencies interested in identifying novel approaches to addressing cost and access to care in HICs. We solicited expert feedback and consensus on an empirically-derived set of criteria to create a practical tool for funders that can be used directly and tested prospectively using current databases of LMIC programs.

Are global and regional improvements in life expectancy and in child, adult and senior survival slowing?

Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year2. Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health-primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest.

Immunochromatographic strip assay development for avian influenza antibody detection.

To detect antibody on pen-side is a rapid way to know the avian influenza (AI) infectious status in a chicken flock. The purpose of this study was to develop an immunochromatographic strip (ICS) assay to detect the antibody against the AI virus (AIV) for field applications. The ICS was constructed by fixing an AIV strain A/chicken/Taiwan/2838V/2000 (H6N1) onto a nitrocellulose membrane as the antigen at the test line and goat anti-rabbit IgG antibody at the control line. The colloidal gold conjugated with rabbit anti-chicken IgG was used as the tracer. The present ICS was used to detect antibodies against avian influenza virus in 326 chicken serum samples from the field. Compared with HI, this ICS could detect antibodies against H5 and H6 AIVs. The hemagglutination inhibition (HI) test was used as the standard to evaluate the ICS accuracy. The results showed that the sensitivity and specificity of this ICS reached 95.2% (159/167) and 94.3% (150/159), respectively. The Kappa value of the HI and ICS was 0.896 (P < 0.001). In conclusion, this ICS could be used as a rapid test to detect antibodies against AIVs in the field.

Visualization of subunit interactions and ternary complexes of protein phosphatase 2A in mammalian cells.

Protein phosphatase 2A (PP2A) is a ubiquitous phospho-serine/threonine phosphatase that controls many diverse cellular functions. The predominant form of PP2A is a heterotrimeric holoenzyme consisting of a scaffolding A subunit, a variable regulatory B subunit, and a catalytic C subunit. The C subunit also associates with other interacting partners, such as α4, to form non-canonical PP2A complexes. We report visualization of PP2A complexes in mammalian cells. Bimolecular fluorescence complementation (BiFC) analysis of PP2A subunit interactions demonstrates that the B subunit plays a key role in directing the subcellular localization of PP2A, and confirms that the A subunit functions as a scaffold in recruiting the B and C subunits to form a heterotrimeric holoenzyme. BiFC analysis also reveals that α4 promotes formation of the AC core dimer. Furthermore, we demonstrate visualization of specific ABC holoenzymes in cells by combining BiFC and fluorescence resonance energy transfer (BiFC-FRET). Our studies not only provide direct imaging data to support previous biochemical observations on PP2A complexes, but also offer a promising approach for studying the spatiotemporal distribution of individual PP2A complexes in cells.

Computational modeling of drug distribution in the posterior segment of the eye: effects of device variables and positions.

A computational model was developed to simulate drug distribution in the posterior segment of the eye after intravitreal injection and ocular implantation. The effects of important factors in intravitreal injection such as injection time, needle gauge and needle angle on the ocular drug distribution were studied. Also, the influences of the position and the type of implant on the concentration profile in the posterior segment were investigated. Computational Fluid Dynamics (CFD) calculations were conducted to describe the 3D convective-diffusive transport. The geometrical model was constructed based on the human eye dimensions. To simulate intravitreal injection, unlike previous studies which considered the initial shape of the injected drug solution as a sphere or cylinder, the more accurate shape was obtained by level-set method in COMSOL. The results showed that in intravitreal injection the drug concentration profile and its maximum value depended on the injection time, needle gauge and penetration angle of the needle. Considering the actual shape of the injected solution was found necessary to obtain the real concentration profile. In implant insertion, the vitreous cavity received more drugs after intraocular implantation, but this method was more invasive compared to the periocular delivery. Locating the implant in posterior or anterior regions had a significant effect on local drug concentrations. Also, the shape of implant influenced on concentration profile inside the eye. The presented model is useful for optimizing the administration variables to ensure optimum therapeutic benefits. Predicting and quantifying different factors help to reduce the possibility of tissue toxicity and to improve the treatment efficiency.

Lecithin-linker formulations for self-emulsifying delivery of nutraceuticals.

Lecithin-linker microemulsions are formulations produced with soybean lecithin in combination with a highly lipophilic (lipophilic linker) and highly hydrophilic (hydrophilic linkers) surfactant-like additives. In this work, lecithin-linker systems were formulated to produce self-emulsifying delivery systems for ß-carotene and ß-sitosterol. The concentration of the lipophilic linker, sorbitan monooleate, was adjusted to minimize the formation of liquid crystals. The concentration of hydrophilic linkers, decaglyceryl caprylate/caprate and PEG-6-caprylic/capric glycerides, was gradually increased (scanned) until single phase clear microemulsions were obtained. For these scans, the oil (ethyl caprate) to water ratio was set to 1. The single phase, clear microemulsions were diluted with fed-state simulated intestinal fluid (FeSSIF) and produced stable emulsions, with drop sizes close to 200 nm. Using pseudo-ternary phase diagrams to evaluate the process of dilution of microemulsion preconcentrates (mixtures of oil, lecithin and linkers with little or no water) with FeSSIF, it was determined that self-emulsifying systems are obtained when the early stages of the dilution produce single phase microemulsions. If liquid crystals or multiple phase systems are obtained during those early stages, then the emulsification yields unstable emulsions with large drop sizes. An in vitro permeability study conducted using a Flow-Thru Dialyzer revealed that stable emulsions with drop sizes of 150-300 nm produce large and irreversible permeation of ß-carotene to sheep intestine. On the other hand, unstable emulsions produced without the linker combination separated in the dialyzer chamber.

Estimating oxygen needs for childhood pneumonia in developing country health systems: a new model for expecting the unexpected.

BACKGROUND: Planning for the reliable and cost-effective supply of a health service commodity such as medical oxygen requires an understanding of the dynamic need or 'demand' for the commodity over time. In developing country health systems, however, collecting longitudinal clinical data for forecasting purposes is very difficult. Furthermore, approaches to estimating demand for supplies based on annual averages can underestimate demand some of the time by missing temporal variability. METHODS: A discrete event simulation model was developed to estimate variable demand for a health service commodity using the important example of medical oxygen for childhood pneumonia. The model is based on five key factors affecting oxygen demand: annual pneumonia admission rate, hypoxaemia prevalence, degree of seasonality, treatment duration, and oxygen flow rate. These parameters were varied over a wide range of values to generate simulation results for different settings. Total oxygen volume, peak patient load, and hours spent above average-based demand estimates were computed for both low and high seasons. FINDINGS: Oxygen demand estimates based on annual average values of demand factors can often severely underestimate actual demand. For scenarios with high hypoxaemia prevalence and degree of seasonality, demand can exceed average levels up to 68% of the time. Even for typical scenarios, demand may exceed three times the average level for several hours per day. Peak patient load is sensitive to hypoxaemia prevalence, whereas time spent at such peak loads is strongly influenced by degree of seasonality. CONCLUSION: A theoretical study is presented whereby a simulation approach to estimating oxygen demand is used to better capture temporal variability compared to standard average-based approaches. This approach provides better grounds for health service planning, including decision-making around technologies for oxygen delivery. Beyond oxygen, this approach is widely applicable to other areas of resource and technology planning in developing country health systems.

Removal of trichloroethylene by zerovalent iron/activated carbon derived from agricultural wastes.

Activated carbon (AC) and zerovalent iron (ZVI) have been widely used in the adsorption and dehalogenation process, respectively, for the removal of organic compounds in environmental treatments. This study aims to prepare ZVI/AC derived from an agricultural waste, coir pith, through simple one-step pyrolysis. The effect of activation temperature and time on the surface area, iron content, and zerovalent iron ratio of ZVI/AC was systemically investigated. The results indicated that the activation of AC by FeSO4 significantly increased surface area of AC and distributed elemental iron over the AC. The X-ray diffraction (XRD), electron spectroscopy for chemical analysis (ESCA), and X-ray absorption near edge structure (XANES) spectra of ZVI/AC revealed that zerovalent iron was present. As compared to AC without FeSO4 activation, ZVI/AC increased the trichloroethylene removal rate constant by 7 times. The dechlorination ability of ZVI/AC was dominated by the zerovalent iron content. We have shown that lab-made ZVI/AC from coir pith can effectively adsorb and dehalogenate the chlorinated compounds in water.

Retina-choroid-sclera permeability for ophthalmic drugs in the vitreous to blood direction: quantitative assessment.

PURPOSE: To determine the outward permeability of retina-choroid-sclera (RCS) layer for different ophthalmic drugs and to develop correlations between drug physicochemical properties and RCS permeability. METHODS: A finite volume model was developed to simulate pharmacokinetics in the eye following drug administration by intravitreal injection. The RCS permeability was determined for 32 compounds by best fitting the drug concentration-time profile obtained by simulation with previously reported experimental data. Multiple linear regression was then used to develop correlations between best fit RCS permeability and drugs physicochemical properties. RESULTS: The RCS drug permeabilities had values that ranged over 3 × 10(-6) m/s. Regression analysis for hydrophilic compounds showed that more than 92% of the variation in permeability values can be explained by correlative models of drug properties that include logarithm of the octanol-water partition coefficient (LogP), protein binding (PB), number of hydrogen bond acceptors (HBA), hydrogen bond donors (HBD), polar surface area (PSA) and dissociation constant (pKa) as independent variables. Regression analysis for lipophilic compounds showed that no significant correlation can be found between just physicochemical properties and RCS permeability. CONCLUSION: Using the RCS permeability obtained from this study for different drugs, one can predict pharmacokinetics of intravitreal drug delivery systems such as solid implants or colloidal systems. Furthermore, the developed correlations between RCS permeability and physicochemical properties of drugs are useful in early drug development by predicting RCS permeability and drug concentration in the vitreous without experimental data.

Global divergence in critical income for adult and childhood survival: analyses of mortality using Michaelis-Menten.

Life expectancy has risen sharply in the last 50 years. We applied the classic Michaelis-Menten enzyme kinetics to demonstrate a novel mathematical relationship of income to childhood (aged 0-5 years) and adult (aged 15-60 years) survival. We treat income as a substrate that is catalyzed to increase survival (from technologies that income buys) for 180 countries from 1970 and 2007. Michaelis-Menten kinetics permit estimates of maximal survival and, uniquely, the critical income needed to achieve half of the period-specific maximum. Maximum child and adult survival rose by about 1% per year. Critical incomes fell by half for children, but doubled for men. HIV infection and smoking account for some, but not all, of the rising critical incomes for adult survival. Altering the future cost curve for adult survival will require more widespread use of current interventions, most notably tobacco control, but also research to identify practicable low-cost drugs, diagnostics, and strategies.DOI:http://dx.doi.org/10.7554/eLife.00051.001.

Effect analysis of chemoradiotherapy after operation in patients with stage III A non-small cell lung cancer.

OBJECTIVE: To investigate the effect of chemoradiotherapy after surgery on III A stage non-small cell lung cancer (NSCLC). METHODS: A total of 156 NSCLC patients undergoing total pneumonectomy or pulmonary lobectomy were included in this study. The chemotherapy group (n=75) received the protocol of cisplatin (DDP) + gemcitabine (GEM) / docetaxel (DOC) / vinorelbine (NVB); the radiotherapy + chemotherapy group (n=81) received sequential chemoradiotherapy. The response rate, local control rate in 1 to 2 years, overall survival (OS), progression-free survival (PFS) and adverse reactions were evaluated. RESULTS: The overall response rate was obviously higher in radiotherapy + chemotherapy group (79.4%) than in chemotherapy group (56.8%) (P<0.01). The 1 year local control rates for chemotherapy group and radiotherapy + chemotherapy group were (69.1±7.9)% and (77.8±8.2)% respectively and the difference reached statistical significance (P<0.001). The 2 year local control rates were (42.1±6.1)% and (61.5±6.9)% respectively (P<0.001). The difference in median follow-up time between the two groups did not reach statistical meaning (P>0.05), while the median PFS of two groups were 10.8 months and 16.9 months respectively (P<0.001). 1-year and 3-year survival rates were obviously higher in radiotherapy + chemotherapy group than in chemotherapy group, and the difference reached statistical significance (P<0.05 or P<0.01). The adverse reactions manifested as hematological toxicity and digestive tract reaction in the two groups. In the radiotherapy + chemotherapy group, incidences of radiation-induced esophagus injury and lung injury were 24.7% and 34.6% respectively, all occurring within 2 to 6 weeks after the start of radiation and both below grade 2. CONCLUSIONS: Chemoradiotherapy after surgery can improve local control rate and reduce or prevent distant metastasis, but there are still many controversies. In clinical work, we should carefully evaluate each patient's age, lung function, basic physical condition scoring and complications to choose a therapeutic schedule that is suitable for the patient.

Lecithin-linker microemulsion gelatin gels for extended drug delivery.

This article introduces the formulation of alcohol-free, lecithin microemulsion-based gels (MBGs) prepared with gelatin as gelling agent. The influence of oil, water, lecithin and hydrophilic and lipophilic additives (linkers) on the rheological properties and appearance of these gels was systematically explored using ternary phase diagrams. Clear MBGs were obtained in regions of single phase microemulsions (µEs) at room temperature. Increasing the water content in the formulation increased the elastic modulus of the gels, while increasing the oil content had the opposite effect. The hydrophilic additive (PEG-6-caprylic/capric glycerides) was shown to reduce the elastic modulus of gelatin gels, particularly at high temperatures. In contrast to anionic (AOT) µEs, the results suggest that in lecithin (nonionic) µEs, the introduction of gelatin "dehydrates" the µE. Finally, when the transdermal transport of lidocaine formulated in the parent µE and the resulting MBG were compared, only a minor retardation in the loading and release of lidocaine was observed.

The hydrophobicity of silicone-based oils and surfactants and their use in reactive microemulsions.

In this work, for the first time, the Hydrophilic-Lipophilic Difference (HLD) framework for microemulsion formulation has been applied to silicone oils and silicone alkyl polyether surfactants. Based on the HLD equations and recently introduced mixing rules, we have quantified the hydrophobicity of the oils according to the equivalent alkane carbon number (EACN). We have found that, in a reference system containing sodium dihexyl sulfosuccinate (SDHS) as the surfactant, 0.65 centistoke (cSt) and 3.0 cSt silicone oils behave like n-dodecane and n-pentadecane, respectively. Silicone alkyl polyether surfactants were found to have characteristic curvatures ranging 3.4-18.9, exceeding that of most non-ionic surfactants. The introduction of methacrylic acid (MAA) and hydroxyethyl methacrylate (HEMA) to the aqueous phase caused a significant negative shift in HLD, indicative of an aqueous phase that is less hydrophilic than pure water. The more hydrophobic surfactants (largest positive curvatures) were used in order to compensate for this effect. These findings have led to the formulation of bicontinuous microemulsions (µEs) containing silicone oil, silicone alkyl polyether and reactive monomers in aqueous solution. Ternary phase diagrams of these systems revealed the potential for silicone-containing polymer composites with bicontinuous morphologies. These findings have also helped to explain the phase behavior of formulations previously reported in literature, and could help in providing a systematic, consistent approach to future silicone oil based microemulsion formulation.