Embolization Techniques for Arteriovenous Malformations in Parkes-Weber Syndrome.

BACKGROUND: Multiple high-flow arteriovenous malformations (AVMs) are the hallmark of Parkes-Weber syndrome (PWS). Surgical resection has historically shown poor outcomes with PWS. The aim of this study was to assess the management of PWS in the current era. METHODS: A retrospective review was performed from 2004 to 2017 on all patients presenting to a single institution for the management of PWS. Presentation, techniques, complications, and outcomes were reviewed. RESULTS: Fourteen patients (50% male) with PWS were seen at our institution, and mean age was 19.9 years (range, 4.7-68.8). The lower extremity was affected in 12 (86%) and the upper extremity in 2 (14%) patients. All patients presented with pain and swelling in the affected limb. Seven (50%) patients presented with ulcers, of which 3 (43%) had extensive wounds. Five (36%) patients had echocardiographic evidence of high-output cardiac failure. All patients underwent angiography with the intention to treat. Three (21%) patients were found to have diffuse arteriovenous communication with no discrete AVM nidus and thus did not undergo intervention. The remaining 11 (79%) patients underwent transcatheter embolization of the AVM's arterial inflow. Six (55%) patients required multiple or staged inflow embolization procedures, with a mean of 3.3 (range, 1-10) interventions. Thirty-two arterial embolization procedures were performed in total. n-Butyl-2-cyanoacrylate (nBCA) adhesive was used in 22 (69%), microspheres in 8 (25%), and a combination of coils and nBCA adhesive in 2 (6%) cases. Technical angiographic success was seen in all patients. Six (55%) patients also had interventions to treat the venous component of the malformation, either concomitantly or during a separate procedure. This included radiofrequency ablation in 1 (17%), coil embolization in 1 (17%), sodium tetradecyl sulfate (STS) sclerotherapy in 2 (33%), and a combination of STS, coil embolization, and vein stripping in 2 (33%) patients. Ten (91%) patients experienced a partial response and 1 (9%) patient experienced no response to treatment. No patients had a complete response, as expected with the diffuse nature of this disease. There were no periprocedural complications. Two of 3 patients with complex wounds required major amputations for gangrene, including one above-knee and one below-knee amputation at 128 months and 66 months after the index procedure, respectively. CONCLUSIONS: AVMs in PWS can be successfully treated by a transcatheter approach. Multiple interventions are usually required. Patients with extensive wounds remain at risk for loss of limb.

Major Limb Amputations in Patients with Congenital Vascular Malformations.

BACKGROUND: The need for major amputations in patients with vascular malformations is rare. This study reviews our contemporary experience with major amputations in patients with vascular malformations. METHODS: A retrospective review from April 2014 to November 2018 identified 993 patients undergoing management of a vascular malformation involving the upper or lower extremity at a tertiary center. This population was analyzed to identify those requiring either a transfemoral or transhumeral amputation. This cohort was investigated for clinical course, surgical procedures, and outcomes. RESULTS: Five patients (0.5%) underwent major amputation, including 3 transhumeral and 2 above-knee amputations. The median age was 37.8 years (interquartile range (IQR): 25.4-40.2), and 2 (40%) were male. Four (80%) patients had high-flow arteriovenous malformations, including 1 (20%) with Parkes-Weber syndrome. One (20%) patient had a low-flow venous malformation associated with Klippel-Trénaunay syndrome. All patients had malformation extending into the chest or pelvis, with the amputation being at the level of residual malformation. As such, amputation had been initially felt to be high risk because of the proximal extent of the lesions. Before amputation, a median of 11 procedures (IQR: 4-39) were performed per patient. This included 29 transarterial embolizations, 4 transvenous embolizations, 20 direct stick embolizations, 3 debulking procedures, 38 debridements, 6 skin grafts or muscle flaps, and 4 minor amputations. The median time course of treatment before amputation was 117 months (IQR: 44-171). Indications for major amputation included chronic pain and recurrent bleeding in all 5 (100%) patients, loss of function in 2 (40%), nonhealing wounds in 2 (40%), and sepsis in 1 (20%) patient. There were no perioperative deaths. The median blood loss was 1,000 mL (IQR: 650-2,750). All patients required transfusion of packed red blood cells with a mean of 1.6 units (standard deviation: 0.54). Transhumeral amputation was facilitated by transcatheter embolization in 1 (33%) and an occlusion balloon within the subclavian artery in 2 (66%) patients. The median length of stay was 6 days (IQR: 5-13). The median length of follow-up was 132 months (IQR: 68-186) from initial intervention and 12 months (IQR: 8-31) from amputation. Two patients (40%) who had undergone transhumeral amputation required revision of the amputation site for recurrent ulceration at 2 and 38 months. Of these, 1 patient underwent 3 transcatheter embolization procedures before revision and 1 underwent 1 embolization after revision. CONCLUSIONS: Although rare, successful amputation at the level of residual malformation can be performed in select patients with refractory complications of vascular malformations including intractable pain, bleeding, or nonhealing wounds. Specific preoperative and intraoperative measures may be critical to achieve satisfactory outcomes, and endovascular techniques continue to play a role after amputation.

Complexity of Aortic Arch Anatomy Affects the Outcomes of Transcarotid Artery Revascularization Versus Transfemoral Carotid Artery Stenting.

BACKGROUND: Transcarotid artery revascularization (TCAR) has been shown to have half the rates of transient ischemic attack (TIA), stroke, and death compared with transfemoral carotid artery stenting (TFCAS). Successful outcomes of TFCAS require careful patient selection. The aim of this study was to determine the outcomes of TFCAS versus TCAR in both simple (type I) and complex (type II and III) aortic arches. METHODS: A retrospective cohort study was performed comparing the outcomes of patients undergoing TFCAS versus TCAR with simple and complex aortic arches using the Vascular Quality Initiative registry from August 2011 to May 2019. The primary outcome was a composite of in-hospital TIA/stroke/death. RESULTS: About 6,108 carotid artery interventions were analyzed, including 3,536 (57.9%) patients with type I, 2,013 (33.0%) with type II, and 559 (9.2%) with type III aortic arch. In 3,535 patients with a simple arch, 1,917 underwent TFCAS and 1,619 had TCAR. Mean age was 70.6 (±9.5) years, and 2,382 (67.4%) patients were males. The primary outcome of postoperative TIA/stroke/death was seen significantly less frequently in those undergoing TCAR compared with TFCAS in simple arches (odds ratio [OR], 0.63; 95% confidence interval [95% CI], 0.43-0.94; P = 0.0236). Although the individual outcome of death occurred less often in TCAR (P = 0.0025), there was no difference in the occurrence of in-hospital stroke (P = 0.8836) or TIA (P = 0.4608). On multivariable analysis, TCAR was associated with improved outcomes (P = 0.0062). A worse outcome was associated with increasing age (P < 0.001), a prior stroke (P < 0.0001), and increasing number of stents (P = 0.0483). In 2,572 patients with a complex arch, 1,416 underwent TFCAS and 1,156 had TCAR. Mean age was 73.0 (±9.1) years, and 1,655 (64.4%) were males. In complex arch anatomy, the primary outcome of in-hospital TIA/stroke/death was seen significantly less frequently in TCAR compared with TFCAS (OR, 0.49; 95% CI, 0.31-0.77; P = 0.0022). Again noted was a significant difference in death, with better outcomes in TCAR (P = 0.0133). Although the occurrence of in-hospital TIA was no different between the 2 approaches (P = 0.6158), there were significantly fewer strokes in those treated with TCAR (P = 0.0132). TCAR (P = 0.0146) was associated with improved outcomes. A worse outcome was seen with advancing age (P = 0.0003), prior strokes (P = 0.01), and a left-sided lesion (P = 0.0176). CONCLUSIONS: TCAR has improved outcomes of TIA/stroke/death compared with TFCAS in both simple and complex aortic arch anatomy. In simple aortic arches, there is no difference in neurologic outcomes between both approaches. In complex arch anatomy, TCAR has fewer strokes.

Cross-clamp location affects short-term survival in patients undergoing open abdominal aortic aneurysm repair.

INTRODUCTION: Open abdominal aortic aneurysm (oAAA) repair in the era of advanced endovascular aortic techniques is used in challenging anatomy. The impact of the location of the proximal aortic cross-clamp (suprarenal [SR] vs infrarenal [IR]) on outcomes remains to be determined. The aim of this study was to analyze the effect of proximal aortic cross-clamp location on short-term and overall survival after oAAA repair in a contemporary series. METHODS: A retrospective cohort study was performed comparing the outcomes of patients undergoing oAAA repair with SR and IR aortic cross-clamping using the Vascular Quality Initiative registry from January 2003 to September 2018. Our primary end point was short-term mortality. RESULTS: There were 7601 patients who underwent oAAA repair. Their mean age was 69.3 ± 8.5 years and 5555 patients (73.1%) were male. The aortic cross-clamp location was IR in 4044 patients (53.2%). The SR group had increased maximum AAA diameter (58 mm vs 56 mm; P < .0001), hypertension (85.5% vs 82.0%; P < .0001), preoperative creatinine (1.11 vs 1.08; P = .001), and were more likely to be in American Society of Anesthesiologists class IV (37.4% vs 30.6%; P < .0001). Postoperative renal failure occurred significantly more often in the SR group (24.4 vs 11.4%; P < .0001). Short-term mortality was 2.7% in the IR group and 4.7% in the SR group (P < .0001). Kaplan-Meier survival estimates were 93.7% and 83.8% in the IR group and 90.9% and 81.2% in the SR group at 1 and 5 years, respectively (P = .007). Multivariable analysis demonstrated that SR cross-clamping was significantly associated with short-term mortality (hazard ratio, 1.38; 95% confidence interval, 1.07-1.78; P = .01); however, it did not affect overall survival (hazard ratio, 1.13; 95% confidence interval, 1.00-1.28; P = .06). CONCLUSIONS: A SR cross-clamp location is associated with an increased short-term mortality in patients undergoing oAAA repair. Overall survival is not affected by a SR cross-clamp location.

Determination of optimal loading and maintenance doses for continuous infusion of vancomycin in critically ill patients: Population pharmacokinetic modelling and simulations for improved dosing schemes.

OBJECTIVES: Despite extensive clinical use, limited data are available on optimal loading and maintenance doses of vancomycin in critically ill patients. This study aimed to develop a rational approach for optimised dosage of vancomycin given in a continuous infusion in critically ill patients. METHODS: Vancomycin pharmacokinetic (PK) data (total serum concentrations) were obtained from 55 intensive care unit (ICU) patients (Bach Mai Hospital, Hanoi, Vietnam) receiving a 20 mg/kg loading dose followed by continuous infusion stratified by creatinine clearance (CLCr). Population PK modelling and Monte Carlo simulations were performed using a nonlinear mixed-effects modelling (NONMEM) program for a target of 20-30 mg/L to optimise efficacy and minimise nephrotoxicity. RESULTS: A two-compartment model with first-order elimination best fitted the PK data with central and peripheral volumes of distribution of 1.01 and 2.39 L/kg, respectively (allometric scaling to a 70 kg standard subject). The population total clearance of 3.63 L/h was only explained by renal function in the covariate and final model. The simulations showed that a 25-mg/kg loading dose infused over 90 minutes was optimal to reach the target range. The optimal maintenance dose for low renal function (CLCr < 45 mL/min) was 1000-1500 mg/day. For augmented renal clearance (CLCr > 130 mL/min) the dose should be up to 3500 mg/day or even 4500 mg/day to achieve adequate exposure. These simulated maintenance doses were larger than previously proposed for non-ICU patients. CONCLUSION: Large loading and maintenance doses of vancomycin are generally needed in critically ill patients. Because of high interindividual variability in vancomycin PK, drug monitoring may still be necessary.

Health policy and systems research: towards a better understanding and review of ethical issues.

Given the focus on health systems in the post-millennium development goal era and moving towards the sustainable development goals, there is a compelling need for a common framework for health policy and systems research ethics to guide researchers and facilitate review by research ethics committees. A consultation of global health policy and systems research and ethics experts was convened to identify ethical considerations relevant to health policy and systems research based on existing knowledge and to identify knowledge gaps through a scoping review and further expert deliberation. Health policy and systems research is highly complex and, in the absence of guidance documents, there is significant variability in ethics review. Although fundamental ethical principles pertain to both traditional clinical research and health policy and systems research, the application of these principles requires a comprehensive understanding of the nature of health policy and systems research with its distinct challenges. Such awareness must be raised among researchers and research ethics committees. Current research ethics committees lack familiarity with health policy and systems research and because health policy and systems research is conducted in real-world contexts, committees often have difficulties in determining whether a project is indeed research and/or requires ethical review. Given the strong current focus on health policy and systems research to rapidly improve health and health systems functioning globally, greater engagement and dialogue around the ethical concerns is required to optimise research review and research conduct in this rapidly evolving field.

Investigación sobre la implementación de políticas de salud

Uno de los principales retos que afronta la comunidad global de salud consiste en identificar la manera de adoptar intervenciones de eficacia demostrada y aplicarlas en la práctica. Hay intervenciones probadas que permiten salvar vidas y hacer frente a muchos de los problemas de salud que afrontamos, pero no se conoce suficientemente la mejor manera de realizar esas intervenciones en toda la gama de sistemas de salud existentes y en la amplia diversidad de entornos posibles. Nuestro fracaso para aplicar efectivamente las intervenciones tiene un precio. Por ejemplo, cada año, más de 287.000 mujeres mueren por complicaciones relacionadas con el embarazo y el parto, y unos 7,6 millones de niños, entre ellos 3,1 millones de recién nacidos, mueren por enfermedades prevenibles o tratables mediante intervenciones existentes. COMPRENSIÓN DE LA IMPLEMENTACIÓN EN EL MUNDO REAL Las cuestiones relativas a la implementación surgen como resultado de diversos factores, incluidos elementos contextuales del “mundo real” que se han pasado por alto o no se han incluido en otras disciplinas de investigación. La investigación sobre la implementación de políticas arroja luz sobre esos factores y sienta las bases para la adopción de decisiones apropiadas al contexto y basadas en pruebas científicas, que es crucial para hacer realidad lo que en teoría es posible. Dado que la investigación sobre la implementación de políticas está integrada en la realidad, quienes trabajan en el mundo real (prácticos, en oposición a los “investigadores”) suelen plantear preguntas que son el punto de partida de nuevas ideas. Uno de los principales retos que afrontan los investigadores sobre la implementación consiste en velar por que esas preguntas sean escuchadas, y que la investigación realizada se oriente a darles respuesta, y no a los temas que los investigadores pudieran considerar interesantes. UNA HERRAMIENTA PRÁCTICA Integrada en el mundo real, la investigación sobre la implementación de políticas es también una herramienta poderosa para obtener y analizar información en tiempo real, lo que permite la evaluación del desempeño, por ejemplo, y facilita el fortalecimiento de los sistemas de salud. La investigación sobre la implementación de políticas es particularmente importante para apoyar la ampliación a escala de las intervenciones y su integración en los sistemas de salud a nivel nacional. Con demasiada frecuencia, algunas intervenciones que resultan eficaces en estudios piloto a pequeña escala no logran cumplir con las expectativas cuando se las aplica en estrategias nacionales, o no se pueden trasladar de un país a otro en razón de diferencias contextuales. La investigación sobre la implementación de políticas ayuda a aclarar por qué ocurre eso, y se puede utilizar en apoyo del proceso de perfeccionamiento constante necesario para la adecuada adaptación. Las mismas capacidades convierten a la investigación sobre la implementación de políticas en una herramienta útil para ayudar a las organizaciones a fortalecer su capacidad de aprendizaje con miras a asimilar y poner en práctica los conocimientos desarrollados regularmente. UN ESFUERZO DE COLABORACIÓN La investigación sobre la implementación de políticas es de máxima utilidad cuando los encargados de la ejecución toman parte en las fases de identificación, diseño y realización de la investigación llevada a cabo. Por eso es tan importante el fomento de los vínculos de colaboración entre las partes interesadas participantes en la formulación de políticas, la gestión de programas y la investigación. Una manera de apoyar la colaboración entre investigadores y encargados de la ejecución consiste en integrar la investigación sobre la implementación de políticas en los procesos de toma de decisiones políticas y programáticas desde el principio, en vez de considerarla cómo un esfuerzo separado del proceso de implementación. De esa manera, la investigación científica también se puede integrar de forma sistemática y constante en el proceso destinado a solucionar los problemas de la implementación. Además, la investigación sobre la implementación de políticas puede desempeñar un papel importante como una herramienta ue facilite a las comunidades de base la identificación de cuestiones desatendidas, la revelación de deficiencias en el desempeño y el fortalecimiento de la rendición de cuentas de las organizaciones de salud. En todos estos esfuerzos de colaboración se insta a los investigadores sobre la implementación de políticas a ser receptivos y flexibles en sus trabajos. De hecho, el conocimiento del contexto y los sistemas, así como la flexibilidad para identificar enfoques metodológicos apropiados, pueden ser tan importantes o más que el seguimiento riguroso de un diseño de investigación fijo. UNA GRAN DIVERSIDAD DE INVESTIGACIONES En general, el término “investigación sobre la implementación de políticas” describe el estudio científico de los procesos utilizados para aplicar iniciativas, así como los factores contextuales que afectan esos procesos. Ello puede abordar o examinar cualquier aspecto de la implementación, especialmente los factores que la afecten (tales como la pobreza, el aislamiento geográfico, las creencias tradicionales), los procesos de implementación en sí mismos (por ejemplo, la distribución gratuita de mosquiteros tratados con insecticidas a través de dispensarios de salud materna, o la vacunación masiva frente a medidas de vigilancia y confinamiento), y los resultados o productos finales de la implementación objeto de estudio. La investigación sobre la implementación de políticas es relevante y aplicable a muchos campos de investigación diferentes y en diversos grados, en función del tema que se estudie. Por ejemplo, generalmente, la investigación básica de nuevos medicamentos no abarca ninguna cuestión relativa a la implementación, mientras que sí lo hacen las medidas orientadas a asegurar la disponibilidad de esos medicamentos para quienes los necesitan. La investigación sobre la implementación de políticas suele centrarse en las estrategias necesarias para realizar y poner en práctica nuevas intervenciones aquí llamadas “estrategias de implementación”, un término utilizado para distinguirlas de las intervenciones clínicas y de salud pública. Para estudiar los procesos de implementación se puede utilizar un marco que permita conceptualizar y medir los resultados de la implementación sobre la base de variables tales como la “aceptabilidad”, “idoneidad” y “viabilidad”, a fin de comprender en qué medida está funcionando efectivamente un determinado proceso de implementación. UNA AMPLIA GAMA DE ENFOQUES Habida cuenta de la gran diversidad de enfoques y disciplinas de investigación empleados, tiene poco sentido hablar de un conjunto de “métodos de investigación sobre la implementación de políticas”. Sin embargo, algunos enfoques y diseños de investigación, incluidos los ensayos pragmáticos, los ensayos híbridos de efectividad de la implementación, los estudios sobre mejoramiento de la calidad y la investigación acción participativa son particularmente útiles, por cuanto generan información práctica, son eficaces para detectar las sutilezas contextuales a lo largo del tiempo y ofrecen la flexibilidad iterativa necesaria para responder al cambio. Si bien esos instrumentos son vitales para el investigador de la implementación, es importante tener en cuenta que en la investigación sobre la implementación de políticas “la pregunta es rey”, es decir, el tipo de preguntas determina el método utilizado, y no viceversa. Las preguntas de la investigación sobre la implementación de políticas suelen ser complejas y reflejar la amplia gama de factores contextuales que pueden influir en la implementación, producir efectos impredecibles y exigir que los encargados de la ejecución realicen adaptaciones constantemente. Para abarcar esa complejidad se requiere una flexibilidad considerable por parte de los investigadores, especialmente en lo que respecta al carácter complejo y dinámico de la materia que se estudia. ARMONIZAR LA INVESTIGACIÓN CON LAS NECESIDADES Y ASEGURAR LA CALIDAD En circunstancias ideales, la investigación sobre implementación de políticas se debería armonizar con las necesidades, o sea, abordar las inquietudes de los destinatarios previstos y responder a las particularidades del tema que se analiza. En ese contexto, el grado de certeza exigido respecto de los resultados o proyecciones es una consideración fundamental. Por ejemplo, un encargado de formular políticas que tenga limitaciones en su trabajo podría buscar indicios sólidos de la posible eficacia de una intervención, pero no dispondrá necesariamente del tiempo requerido para realizar estudios multianuales que le darían un mayor grado de certeza. El objetivo de responder a las necesidades de diferentes audiencias podría tener importantes repercusiones en el diseño básico, el presupuesto y el calendario de la investigación. A fin de asegurar la armonización de la investigación sobre implementación de políticas con las necesidades y la buena calidad, es conveniente formular las siguientes preguntas clave: ¿Se aborda claramente en la investigación una cuestión concerniente a la implementación? ¿Se describe con claridad lo que se está implementando (por ejemplo, detalles de la práctica, el programa o la política)? ¿Se incluye en la investigación una estrategia de implementación? Si así fuera, ¿se describe y se examina apropiadamente? ¿Se realiza la investigación en un entorno del mundo real? Si así fuera, ¿se describen esas condiciones con detalle suficiente? ¿Se consideran debidamente en la investigación las variables de los resultados de la implementación? ¿Se examinan apropiadamente en la investigación el contexto y otros factores que influyen en la implementación? ¿Se examinan apropiadamente en la investigación los cambios a lo largo del tiempo y el nivel de complejidad del sistema? ¿Se identifican claramente en la investigación la audiencia destinataria de la investigación y la forma en que se la puede utilizar? APROVECHAR MEJOR LA INVESTIGACIÓN SOBRE LA IMPLEMENTACIÓN DE POLÍTICAS A pesar de su importancia, la investigación sobre la implementación de políticas sigue siendo un ámbito de estudio desatendido, en parte por falta de conocimiento respecto de lo que es y lo que ofrece, y en parte por la escasa inversión realizada en actividades de investigación sobre la implementación de políticas. Se gastan millones en innovaciones de la salud, pero muy poco en determinar la mejor manera de utilizarlas. Este problema nos afecta a todos, pero en particular a las poblaciones de los países de ingresos bajos y medianos en los que los desafíos de la implementación son los más grandes. La presente Guía procura corregir esa falta de conocimiento de la investigación sobre la implementación de políticas y alentar al personal de programas y los encargados de la ejecución a que asuman un mayor compromiso con el tema y reconozcan que la investigación sobre la implementación de políticas es, de hecho, una parte integral de la planificación y ejecución de programas, y no algo que ocurre una vez que los programas están en marcha, y se ejecutan en gran medida para beneficio de otros investigadores. Por su parte, los investigadores en materia de implementación pueden hacer mucho más para interactuar con los encargados de la ejecución y el personal de los programas en el proceso de investigación. Solo mediante la colaboración podrán los encargados de la ejecución con su comprensión minuciosa del contexto, y los investigadores con su conocimiento profundo de los métodos y técnicas de indagación, esperar que comprendamos mejor las cuestiones de la implementación que ponen en riesgo muchos de nuestros esfuerzos de salud pública.

The role of NGOs in child injury prevention: an organizational assessment of one network of NGOs.

Unintentional injuries are estimated to claim the lives of more than 875,000 children each year; millions more live with long-term consequences and permanent disabilities. The epidemiology of injuries has become clearer in the past decade. NGOs need to work in concert with each other to address the global burden of injuries by sharing information. Several NGOs have heeded this call, and the field has seen the emergence of global organizations aimed at highlighting the burden of injuries and streamlining injury prevention activities worldwide. Safe Kids Worldwide Inc. (SKWW) is a global network in 16 countries whose mission is to address the burden of injuries in children under 15 by harnessing the potential of local NGOs. An organizational assessment was conducted of SKWW which included structured organizational assessment, functional organizational mapping and contextual analysis that allowed for an in-depth examination of the strengths and challenges of SKWW's injury prevention approach. Over one year, primary and secondary data were collected and analyzed from headquarters and individual country offices. SKWW appears to be an effective model and has experienced a strong momentum and growth over the last two decades. Global NGOs that address the burden of injuries should start by defining a clear and universal strategic goal, build on local successes, maximize their strengths, and create avenues for stronger country engagement.

Goal setting and knowledge generation through health policy and systems research in low- and middle-income countries.

The importance of health policy and systems research (HPSR) and its role in aiding health system reforms has been increasingly recognized in recent years within the World Health Organization (WHO). An assessment of the 71 WHO Country Cooperation Strategies (CCS) that are publicly available and were published in English in 2012 was completed to determine the extent to which HPSR goals are incorporated at the global level. A review was then conducted using a Medline database search to determine the number of articles published by countries with HPSR goals. Sixty-six out of the 71 (93%) available CCS describe HPSR as an objective or strategy for achieving health system priorities. However, only 52 out of the 66 countries (79%) have any publications involving HPSR during their most recent CCS cycle. This suggests that although health systems strengthening through HPSR is increasingly emphasized by the WHO and country health ministries, actual HPSR progress may still be lacking. There is a need and an opportunity for the WHO and other global health agencies to focus on providing the necessary tools and building HPSR capacity in low- and middle-income countries.

Ethical review of health systems research in low- and middle-income countries: a conceptual exploration.

Given that health systems research (HSR) involves different aims, approaches, and methodologies as compared to more traditional clinical trials, the ethical issues present in HSR may be unique or particularly nuanced. This article outlines eight pertinent ethical issues that are particularly salient in HSR and argues that the ethical review process should be better tailored to ensure more efficient and appropriate oversight of HSR with adequate human protections, especially in low- and middle-income countries. The eight ethical areas we discuss include the nature of intervention, types of research subjects, units of intervention and observation, informed consent, controls and comparisons, risk assessment, inclusion of vulnerable groups, and benefits of research. HSR involving human participants is necessary to ensure health systems strengthening and quality of care and to guide public policy intelligently. Health systems researchers must carefully define their intent and goals and openly clarify the values that may influence the premises and design of protocols. As new types of population-level research activities become more commonplace, it is critical that institutional review board (IRB) and research ethics committee (REC) review processes evolve to evaluate these research protocols in ways that address the nuanced features of these studies.

Embedding health policy and systems research into decision-making processes in low- and middle-income countries.

Attention is increasingly directed to bridging the gap between the production of knowledge and its use for health decision-making in low- and middle-income countries (LMICs). An important and underdeveloped area of health policy and systems research (HPSR) is the organization of this process. Drawing from an interdisciplinary conception of embeddedness, a literature review was conducted to identify examples of embedded HPSR used to inform decision-making in LMICs. The results of the literature review were organized according to the World Health Organization's Building Blocks Framework. Next, a conceptual model was created to illustrate the arrangement of organizations that produce embedded HPSR and the characteristics that facilitate its uptake into the arena of decision-making. We found that multiple forces converge to create context-specific pathways through which evidence enters into decision-making. Depending on the decision under consideration, the literature indicates that decision-makers may call upon an intricate combination of actors for sourcing HPSR. While proximity to decision-making does have advantages, it is not the position of the organization within the network, but rather the qualities the organization possesses, that enable it to be embedded. Our findings suggest that four qualities influence embeddedness: reputation, capacity, quality of connections to decision-makers, and quantity of connections to decision-makers and others. In addition to this, the policy environment (e.g. the presence of legislation governing the use of HPSR, presence of strong civil society, etc.) strongly influences uptake. Through this conceptual model, we can understand which conditions are likely to enhance uptake of HPSR in LMIC health systems. This raises several important considerations for decision-makers and researchers about the arrangement and interaction of evidence-generating organizations in health systems.

Analyzing the sources and nature of influence: how the Avahan program used evidence to influence HIV/AIDS prevention policy in India.

BACKGROUND: Major investments by development partners in low- and middle-income countries (LMICs) often seek to develop a supportive policy environment. There is limited knowledge about the mechanisms that development partners use to influence government policy, or which mechanisms are effective. This study assessed the influence of Avahan, a large HIV/AIDS prevention program in India supported by the Bill and Melinda Gates Foundation, on the development of HIV/AIDS policies in India, particularly the National AIDS Control Program III (NACP III). METHODS: A retrospective assessment of the contributions of Avahan to the development of NACP III was conducted based upon document review and in-depth interviews with key informants, including Avahan staff and staff of implementing partners. This assessment was carried out within a framework centered on three domains: evidence considered by policy and decision-makers; the channel through which influence is exerted; and the target audience for influence. RESULTS: Respondents identified a number of respects in which Avahan influenced NACP III policy, notably, Avahan influenced perception of the feasibility of scaling up services (through a demonstration effect) and Avahan, along with others, helped ensure a strong focus on targeted interventions. Overall Avahan's influence was greatest during policy implementation. While the extent to which research evidence generated by Avahan influenced NACP III was limited, best practice evidence generated by Avahan, including the lessons learned from routine implementation and management, contributed significantly to NACP III. This was largely due to the credibility Avahan had established and strategic 'inside track' communications. CONCLUSION: While studies of knowledge translation typically focus primarily on scientific evidence, this study suggests that other forms of evidence, notably best practice evidence derived from program experience, and disseminated through personal communication, were particularly influential. The framework developed for the paper provides a useful tool to analyze how evidence-based influence is exerted.

Preventing maternal and newborn deaths globally: using innovation and science to address challenges in implementing life-saving interventions.

We have made important progress toward achieving Millennium Development Goals 4 and 5, with an estimated 47% decrease in maternal deaths and 28% decrease in newborn deaths globally since 1990. However, rapidly accelerating this progress is vital because far too many maternal and newborn deaths still occur each day. Fortunately, there are major initiatives underway to enhance global efforts in preventing these deaths, including the United Nations Secretary General's Global Strategy for Women's and Children's Health. We know why maternal and newborn deaths occur, where they occur, and how they occur, and we have highly effective interventions for preventing them. Nearly all (99%) maternal and newborn deaths occur in developing countries where the implementation of life-saving interventions has been a major challenge. Determining how best to meet this challenge will require more intensive interrelated efforts that include not only science-driven guidance on effective interventions, but also strategies and plans for implementing these interventions. Implementation science, defined as "the study of methods to promote the integration of research findings and evidence into healthcare policy and practice," will be key as will innovations in both technologies and implementation processes. We will need to develop conceptual and operational frameworks that link innovation and implementation science to implementation challenges for the Global Strategy. Likewise, we will need to expand and strengthen close cooperation between those with responsibilities for implementation and those with responsibilities for developing and supporting science-driven interventions. Realizing the potential for the Global Strategy will require commitment, coordination, collaboration, and communication-and the women and newborns we serve deserve no less.

Igniting interest in prevention: using firefighter focus groups to inform implementation and enhancement of an urban canvassing program.

CONTEXT: Smoke alarm canvassing is recognized as an empirically based, effective intervention for increasing access to and the presence of smoke alarms in homes. OBJECTIVES: We sought to inform the implementation of an intervention designed to enhance an existing fire department smoke alarm canvassing program through an empirically grounded, participatory process. DESIGN: We conducted a series of focus groups with fire union leaders and firefighters involved with the canvassing program in 1 US city, shared the results with the participants, and presented the resulting recommendations to fire department leadership. SETTING: This research occurred in Baltimore, Maryland. PARTICIPANTS: Focus group participants included firefighters who participate in the Fire Department's smoke alarm canvassing program and representatives from the local firefighters' union. MAIN OUTCOME MEASURES: The focus groups sought to capture firefighters' experiences with and opinions about the canvassing program and how to improve it as well as challenges to canvassing work. RESULTS: We conducted 10 focus groups with 65 participants. Firefighters' perspectives on the canvassing program and their recommendations for improving it were expressed through 3 categories of themes concerning program management, canvassing challenges, and attitudes about the program and the community. We also discuss the process of presenting these findings and recommendations to the participants and the fire department leadership, and describe how implementation of some of the recommendations has progressed. CONCLUSIONS: Both the process and outcomes of this formative work inform how to develop and implement community-based public health interventions in real-world settings through academic-community partnerships. The findings also have implications for how canvassing programs are being implemented.

Drinking and driving in Vietnam: public knowledge, attitudes, and practices.

OBJECTIVE: Injuries are among the 10 leading causes of death for all ages in Vietnam, and road traffic fatalities account for approximately half of those deaths. Despite having what is considered to be one of the most stringent alcohol legislations in the region, alcohol involvement in road traffic crashes remains high. This study aims to illustrate the knowledge, attitudes, and practices around alcohol use and drinking and driving by age and sex in 3 provinces in Vietnam. METHODS: This study was conducted between January and February 2011, surveying randomly selected road users over the age of 17 years at gas stations in 3 provinces: Ha Nam, Ninh Binh, and Bac Giang, Vietnam. Data were collected for one week at each gas station. A knowledge, attitudes, and practices (KAPs) survey was administered in 7 time blocks of 90 min throughout the day, from 07:30 am to 9:30 pm. RESULTS: There were a total of 633 respondents almost evenly divided among the 3 provinces. Males accounted for 69.1 percent of respondents; the majority were 36 years of age or younger. Despite the belief that drinking and driving will increase the risk of a crash, a significant proportion of respondents (44.9%) reported drinking and driving; 56.7 percent admitted to drinking and driving within the last month. Drinking and driving was more common among males, with approximately 60.2 percent indicating a history of drinking and driving. This proportion was particularly high among males aged 17 to 26 (71.4%). It was found that preferred alternatives to drinking and driving when available were leaving with a nondrinker (42%), resting until "feeling conscious" (23%), and drinking less (20%). CONCLUSIONS: This study shows that, in general, alcohol use and drinking and driving remain a problem in Vietnam, a major concern given that the country is rapidly motorizing and likewise increasing the likelihood of road traffic crashes in the absence of effective interventions. To target drinking and driving in Vietnam we call for a multifaceted approach, including social marketing and public education campaigns, enhanced enforcement, and programs that either limit the number of drinks to drivers or young individuals or those that provide alternatives to drinking and driving.

Helmet use among motorcyclists in Cambodia: a survey of use, knowledge, attitudes, and practices.

OBJECTIVE: Road traffic injuries (RTIs) are a leading cause of disability and fatality globally. Motorcycle-related injuries, mainly head injuries, and related deaths and disabilities are a significant contributor to the burden of disease in low- and middle-income countries (LMICs). Helmets have been proven to be an effective way to reduce the risk of head injury. As motorcycle use continually increases in Cambodia, head injuries and related deaths and disabilities are expected to rise. This article aims to assess the current status of helmet use in Cambodia, as well as the knowledge, attitudes, and practices among motorcyclists, in order to assist with better planning and implementation of injury prevention strategies. METHODS: Two separate methodologies were employed for this study. Helmet observations were conducted in Phnom Penh, Kandal, Kampong Speu, Siem Reap, and Kampong Cham to assess the current status of helmet use during the day and at night. Roadside knowledge, attitudes, and practice (KAP) interviews were also conducted in Phnom Penh, Kandal, and Kampong Speu to determine the prevailing beliefs around helmet use in Cambodia. RESULTS: Based on observations, the proportion of helmet wearing across all study sites was 25 percent at night and 43 percent during the day among all motorcyclists. The observed proportion was up to 10 times higher among drivers compared to passengers. The top 3 reasons for always wearing a helmet were lifesaving potential, legal duty, and police fines. Almost 60 percent of respondents said that their use or nonuse of a helmet depended on where they were driving. Helmet quality, price, style, and color were important factors influencing the decision to purchase a helmet. CONCLUSIONS: A paradox appears to exist in Cambodia; though awareness of the benefits of wearing a helmet is high, actual helmet use remains low in the country. Daytime usage is higher than nighttime, and these proportions are significantly higher among drivers compared to passengers. There is a continuing need to improve the proportion of all-day helmet wearing, especially at night and among motorcycle passengers in Cambodia.

Cost effectiveness of strategies to combat road traffic injuries in sub-Saharan Africa and South East Asia: mathematical modelling study.

OBJECTIVE: To identify and estimate the population costs and effects of a selected set of enforcement strategies for reducing the burden of road traffic injuries in developing countries. DESIGN: Cost effectiveness analysis based on an epidemiological model. SETTING: Two epidemiologically defined World Health Organization sub-regions of the world: countries in sub-Saharan Africa with very high adult and high child mortality (AfrE); and countries in South East Asia with high adult and high child mortality (SearD). INTERVENTIONS: Enforcement of speed limits via mobile speed cameras; drink-drive legislation and enforcement via breath testing campaigns; legislation and primary enforcement of seatbelt use in cars; legislation and enforcement of helmet use by motorcyclists; legislation and enforcement of helmet use by bicyclists. MAIN OUTCOME MEASURES: Patterns of injury were fitted to a state transition model to determine the expected population level effects of intervention over a 10 year period, which were expressed in disability adjusted life years (DALYs) averted. Costs were expressed in international dollars ($Int) for the year 2005. RESULTS: The single most cost effective strategy varies by sub-region, but a combined intervention strategy that simultaneously enforces multiple road safety laws produces the most health gain for a given amount of investment. For example, the combined enforcement of speed limits, drink-driving laws, and motorcycle helmet use saves one DALY for a cost of $Int1000-3000 in the two sub-regions considered. CONCLUSIONS: The potential impact of available road safety measures is inextricably bound by the underlying distribution of road traffic injuries across different road user groups and risk factors. Combined enforcement strategies are expected to represent the most efficient way to reduce the burden of road traffic injuries, because they benefit from considerable synergies on the cost side while generating greater overall health gains.

Voluntary medical male circumcision: a framework analysis of policy and program implementation in eastern and southern Africa.

BACKGROUND: Following confirmation of the effectiveness of voluntary medical male circumcision (VMMC) for HIV prevention, the World Health Organization and the Joint United Nations Programme on HIV/AIDS issued recommendations in 2007. Less than 5 y later, priority countries are at different stages of program scale-up. This paper analyzes the progress towards the scale-up of VMMC programs. It analyzes the adoption of VMMC as an additional HIV prevention strategy and explores the factors may have expedited or hindered the adoption of policies and initial program implementation in priority countries to date. METHODS AND FINDINGS: VMMCs performed in priority countries between 2008 and 2010 were recorded and used to classify countries into five adopter categories according to the Diffusion of Innovations framework. The main predictors of VMMC program adoption were determined and factors influencing subsequent scale-up explored. By the end of 2010, over 550,000 VMMCs had been performed, representing approximately 3% of the target coverage level in priority countries. The "early adopter" countries developed national VMMC policies and initiated VMMC program implementation soon after the release of the WHO recommendations. However, based on modeling using the Decision Makers' Program Planning Tool (DMPPT), only Kenya appears to be on track towards achievement of the DMPPT-estimated 80% coverage goal by 2015, having already achieved 61.5% of the DMPPT target. None of the other countries appear to be on track to achieve their targets. Potential predicators of early adoption of male circumcision programs include having a VMMC focal person, establishing a national policy, having an operational strategy, and the establishment of a pilot program. CONCLUSIONS: Early adoption of VMMC policies did not necessarily result in rapid program scale-up. A key lesson is the importance of not only being ready to adopt a new intervention but also ensuring that factors critical to supporting and accelerating scale-up are incorporated into the program. The most successful program had country ownership and sustained leadership to translate research into a national policy and program. Please see later in the article for the Editors' Summary.