Abstract Background To illustrate how (standardised) effect sizes (ES) vary based on calculation method and to provide considerations for improved reporting. Methods Data from three trials of tanezumab in subjects with osteoarthritis were analyzed. ES of tanezumab versus comparator for WOMAC Pain (outcome) was defined as least squares difference between means (mixed model for repeated measures analysis) divided by a pooled standard deviation (SD) of outcome scores. Three approaches to computing the SD were evaluated: Baseline (the pooled SD of WOMAC Pain values at baseline [pooled across treatments]); Endpoint (the pooled SD of these values at the time primary endpoints were assessed); and Median (the median pooled SD of these values based on the pooled SDs across available timepoints). Bootstrap analyses were used to compute 95% confidence intervals (CI). Results ES (95% CI) of tanezumab 2.5 mg based on Baseline, Endpoint, and Median SDs in one study were - 0.416 (- 0.796, - 0.060), - 0.195 (- 0.371, - 0.028), and - 0.196 (- 0.373, - 0.028), respectively; negative values indicate pain improvement. This pattern of ES differences (largest with Baseline SD, smallest with Endpoint SD, Median SD similar to Endpoint SD) was consistent across all studies and doses of tanezumab. Conclusion Differences in ES affect interpretation of treatment effect. Therefore, we advocate clearly reporting individual elements of ES in addition to its overall calculation. This is particularly important when ES estimates are used to determine sample sizes for clinical trials, as larger ES will lead to smaller sample sizes and potentially underpowered studies. Trial Registration Clinicaltrials.gov NCT02697773, NCT02709486, and NCT02528188. standardised (standardised (ES analyzed (outcome mixed analysis (SD scores evaluated treatments treatments]) assessed assessed) timepoints. timepoints . timepoints) 95 CI. CI (CI) (95 25 2 5 2. 0416 0 416 0.41 ( 0796 796 0.796 0.060, 0060 0.060 , 060 0.060) 0195 195 0.19 0371 371 0.371 0.028, 0028 0.028 028 0.028) 0196 196 0373 373 0.373 respectively improvement largest Therefore Clinicaltrialsgov Clinicaltrials gov NCT02697773 NCT NCT02709486 NCT02528188 treatments] 9 (CI (9 041 41 0.4 079 79 0.79 006 0.06 06 019 19 0.1 037 37 0.37 002 0.02 02 NCT0269777 NCT0270948 NCT0252818 04 4 0. 07 7 0.7 00 0.0 01 1 03 3 0.3 NCT026977 NCT027094 NCT025281 NCT02697 NCT02709 NCT02528 NCT0269 NCT0270 NCT0252 NCT026 NCT027 NCT025 NCT02 NCT0

BACKGROUND: Sensitisation training can reduce judgemental and discriminatory attitudes amongst healthcare workers. The 'Integrated Key Populations Sensitivity Training Programme for Healthcare Workers in South Africa' aimed to improve access to appropriate and non-judgemental health services for 'key populations', specifically men who have sex with men, sex workers and people who use drugs, through the sensitisation of healthcare workers OBJECTIVES: The aim of this study was to evaluate the effects of the integrated key population sensitisation training intervention for healthcare workers, conducted between 2013 and 2014 in South Africa METHODS: This study used a combination of qualitative and quantitative methods. Qualitative methods compared attitudes between healthcare workers who received the training intervention and those who did not. Quantitative methods were used to compare similar changes in awareness amongst healthcare workers before and after receiving the training. We explored shifts in attitudes towards key populations, changes in awareness of health issues related to stigma, discrimination, and changes in capacity to manage sexual health and HIV risk behaviours, including substance use and anal sex RESULTS: The findings indicate that the training intervention resulted in a shift in attitudes, increased empathy for key populations, a reduction in negative and discriminatory moral-based judgements towards key populations and their behaviours, and increased self-perceived capacity to provide appropriate health services to key populations. Over 70% of healthcare workers trained in this programme strongly agreed that this intervention helped to increase awareness of psychosocial vulnerabilities of key populations, and address stigmatising attitudes CONCLUSION: The findings suggest that sensitisation training increases healthcare workers' knowledge and awareness about specific HIV-related health needs and psychosocial vulnerabilities of key populations, reduces moralising and judgemental attitudes, and results in healthcare workers feeling more skilled to provide appropriate and sensitive services

A holistic environmental flows (EFlows) assessment, undertaken as part of Ecological Reserve determination studies for selected surface water, groundwater, estuaries and wetlands in the Usuthu/Mhlatuze Water Management Area, South Africa, led to recommendations for modified releases from the Jozini Dam to support the socially, economically and ecologically important Pongola Floodplain situated downstream of the dam. The EFlows study analysed various permutations of flow releases from the dam based on the recommendations of pre-dam studies, and augmented by more recent observations, inputs from farmers and fishermen who live adjacent to the floodplain and discussion with the operators of Jozini Dam. The EFlows method used, DRIFT, allowed for the incorporation of detailed information, data and recommendations from a decades-old research project on the Pongola Floodplain that was undertaken prior to the construction of the Jozini Dam into a modern-day decision-making framework. This was used to assess the impact of a series of different flow releases on nature and society downstream of the dam. It was concluded that, within historic volumetric allocations to the floodplain, a release regime could be designed that considerably aided traditional fishing and grazing without necessarily prejudicing other uses, such as agriculture.

BACKGROUND: Men who have sex with men (MSM), sex workers (SW) and people who use drugs (PWUD) are at increased risk for HIV because of multiple socio-structural barriers and do not have adequate access to appropriate HIV prevention, diagnosis and treatment services. OBJECTIVE: To examine the context of access to healthcare experienced by these three 'Key Populations', we conducted a qualitative study in two South African cities: Bloemfontein in the Free State province and Mafikeng in the North West province. METHOD: We carried out in-depth interviews to explore healthcare workers' perceptions, beliefs and attitudes towards Key Populations. Focus group discussions were also conducted with members of Key Populations exploring their experiences of accessing healthcare. RESULTS: Healthcare workers described their own attitudes towards Key Populations and demonstrated a lack of relevant knowledge, skills and training to manage the particular health needs and vulnerabilities facing Key Populations. Female SW, MSM and PWUD described their experiences of stigmatisation, and of being made to feel guilt, shame and a loss of dignity as a result of the discrimination by healthcare providers and other community. members. Our findings suggest that the uptake and effectiveness of health services amongst Key Populations in South Africa is limited by internalised stigma, reluctance to seek care, unwillingness to disclose risk behaviours to healthcare workers, combined with a lack of knowledge and understanding on the part of the broader community members, including healthcare workers. CONCLUSION: This research highlights the need to address the broader healthcare provision environment, improving alignment of policies and programming in order to strengthen provision of effective health services that people from Key Populations will be able to access.

BACKGROUND: Men who have sex with men (MSM) in South Africa experience discrimination from healthcare workers (HCWs), impeding health service access. OBJECTIVES: To evaluate the outcomes of an MSM sensitisation training programme for HCWs implemented in the Western Cape province (South Africa). METHODS: A training programme was developed to equip HCWs with the knowledge, awareness and skills required to provide non-discriminatory, non-judgemental and appropriate services to MSM. Overall, 592 HCWs were trained between February 2010 and May 2012. Trainees completed self-administered pre- and post-training questionnaires assessing changes in knowledge. Two-sample t-tests for proportion were used to assess changes in specific answers and the Wilcoxon rank-sum test for overall knowledge scores. Qualitative data came from anonymous post-training evaluation forms completed by all trainees, in combination with four focus group discussions (n = 28) conducted six months after their training. RESULTS: Fourteen per cent of trainees had received previous training to counsel clients around penile-anal intercourse, and 16% had previously received training around sexual health issues affecting MSM. There was a statistically significant improvement in overall knowledge scores (80% - 87%, p < 0.0001), specifically around penile-anal intercourse, substance use and depression after the training. Reductions in negative attitudes towards MSM and increased ability for HCWs to provide non-discriminatory care were reported as a result of the training. CONCLUSION: MSM sensitisation training for HCWs is an effective intervention to increase awareness on issues pertaining to MSM and how to engage around them, reduce discriminatory attitudes and enable the provision of non-judgemental and appropriate services by HCWs.

Los trabajadores de salud de nivel intermedio (TSNI) son trabajadores capacitados en una institución de educación superior durante al menos dos a tres años, quienes son autorizados y regulados para trabajar de forma autónoma para el diagnóstico, control y tratamiento de dolencias, enfermedades y discapacidades, así como participar en la prevención y promoción de la salud. Su papel se ha ampliado progresivamente y ha recibido atención en particular en países de ingresos bajos y medios, como parte de una estrategia para superar los desafíos del personal sanitario, mejorar el acceso a servicios básicos de salud y lograr objetivos relacionados con los Objetivos del Desarrollo del Milenio. La evidencia, aunque limitada e imperfecta, muestra que donde los TSNI están debidamente capacitados, apoyados y coherentemente integrados en el sistema de salud, tienen el potencial para mejorar la distribución de los trabajadores de la salud y el acceso equitativo a los servicios de salud, manteniendo -si no sobrepasando- los estándares de calidad comparables a los servicios prestados por el personal médico. Sin embargo, existen desafíos importantes en términos de la marginación y el limitado apoyo a la gestión de los TSNI en los sistemas de salud. La expansión de los TSNI debe tener prioridad entre las opciones de política consideradas por países que enfrentan problemas de escasez y desigualdad en la distribución de recursos humanos. Una mejor educación, supervisión, administración y regulación de las prácticas y la integración en el sistema de salud tienen el potencial de maximizar los beneficios de la utilización de este personal.

Mid-level health providers (MLP) are health workers trained at a higher education institution for at least a total of 2-3 years, and authorized and regulated to work autonomously to diagnose, manage and treat illness, disease and impairments, as well as engage in preventive and promotive care. Their role has been progressively expanding and receiving attention, in particular in low- and middle-income countries, as a strategy to overcome health workforce challenges and improve access to essential health services and achieve the health related targets of the Millennium Development Goals. Evidence, although limited and imperfect, shows that, where MLP are adequately trained, supported and integrated coherently in the health system, they have the potential to improve distribution of health workers and enhance equitable access to health services, while retaining quality standards comparable to, if not exceeding, those of services provided by physicians. Significant challenges however exist in terms of the marginalization and more limited management support of MLP in health systems. The expansion of MLP should have priority among the policy options considered by countries facing shortage and maldistribution challenges. Improved education, supervision, management and regulation practices and integration in the health system have the potential to maximize the benefits from the use of these cadres.

Mid-level health providers (MLP) are health workers trained at a higher education institution for at least a total of 2-3 years, and authorized and regulated to work autonomously to diagnose, manage and treat illness, disease and impairments, as well as engage in preventive and promotive care. Their role has been progressively expanding and receiving attention, in particular in low- and middle-income countries, as a strategy to overcome health workforce challenges and improve access to essential health services and achieve the health related targets of the Millennium Development Goals. Evidence, although limited and imperfect, shows that, where MLP are adequately trained, supported and integrated coherently in the health system, they have the potential to improve distribution of health workers and enhance equitable access to health services, while retaining quality standards comparable to, if not exceeding, those of services provided by physicians. Significant challenges however exist in terms of the marginalization and more limited management support of MLP in health systems. The expansion of MLP should have priority among the policy options considered by countries facing shortage and maldistribution challenges. Improved education, supervision, management and regulation practices and integration in the health system have the potential to maximize the benefits from the use of these cadres.

Los trabajadores de salud de nivel intermedio (TSNI) son trabajadores capacitados en una institución de educación superior durante al menos dos a tres años, quienes son autorizados y regulados para trabajar de forma autónoma para el diagnóstico, control y tratamiento de dolencias, enfermedades y discapacidades, así como participar en la prevención y promoción de la salud. Su papel se ha ampliado progresivamente y ha recibido atención en particular en países de ingresos bajos y medios, como parte de una estrategia para superar los desafíos del personal sanitario, mejorar el acceso a servicios básicos de salud y lograr objetivos relacionados con los Objetivos del Desarrollo del Milenio. La evidencia, aunque limitada e imperfecta, muestra que donde los TSNI están debidamente capacitados, apoyados y coherentemente integrados en el sistema de salud, tienen el potencial para mejorar la distribución de los trabajadores de la salud y el acceso equitativo a los servicios de salud, manteniendo -si no sobrepasando- los estándares de calidad comparables a los servicios prestados por el personal médico. Sin embargo, existen desafíos importantes en términos de la marginación y el limitado apoyo a la gestión de los TSNI en los sistemas de salud. La expansión de los TSNI debe tener prioridad entre las opciones de política consideradas por países que enfrentan problemas de escasez y desigualdad en la distribución de recursos humanos. Una mejor educación, supervisión, administración y regulación de las prácticas y la integración en el sistema de salud tienen el potencial de maximizar los beneficios de la utilización de este personal.

Mid-level health providers (MLP) are health workers trained at a higher education institution for at least a total of 2-3 years, and authorized and regulated to work autonomously to diagnose, manage and treat illness, disease and impairments, as well as engage in preventive and promotive care. Their role has been progressively expanding and receiving attention, in particular in low- and middle-income countries, as a strategy to overcome health workforce challenges and improve access to essential health services and achieve the health related targets of the Millennium Development Goals. Evidence, although limited and imperfect, shows that, where MLP are adequately trained, supported and integrated coherently in the health system, they have the potential to improve distribution of health workers and enhance equitable access to health services, while retaining quality standards comparable to, if not exceeding, those of services provided by physicians. Significant challenges however exist in terms of the marginalization and more limited management support of MLP in health systems. The expansion of MLP should have priority among the policy options considered by countries facing shortage and maldistribution challenges. Improved education, supervision, management and regulation practices and integration in the health system have the potential to maximize the benefits from the use of these cadres.

Resumen: El Banco Central Europeo (BCE) emplea "dos pilares" estratégicos para lograr su objetivo de estabilidad de precios dentro la zona del euro. Aun en ausencia de un objetivo monetario explicito, la estabilidad de la relación entre el dinero y los precios mantiene los efectos del papel de los agregados monetarios en la conducción de la política monetaria. La estabilidad de la relación dinero-precios depende a la larga de las propiedades de la demanda por dinero. Este artículo se ocupa de las funciones de la demanda por dinero en los distintos países de la Unión Monetaria Europea, de si tales funciones de demanda pueden ser identificadas, y en caso de que lo sean, si las funciones serán similares en los diferentes países. Un cambio en la tasa de interés del BCE provocaría un cambio idéntico en la tasa de interés en el corto plazo para todos los países de la Unión. Como una consecuencia, el costo de prestar podría además cambiar, lo cual afectará la demanda de préstamos del banco. El tamafío del efecto resultante puede variar de país a país, dependiendo del marco institucional, y ello puede dar lugar a asimetrías en los mecanismos monetarios. Los autores encuentran diferencias significativas en la semi-elasticidad de la tasa de interés de país a país dentro de la Unión: los autores argumentan que esto puede ocasionar serios problemas en la conducción de la política monetaria común por parte del BCE.

Abstract: The European Central Bank (ECB) uses a "two pillar" strategy to achieve its objective of price stability within the euro area. Even in the absence of explicit monetary targeting, stability between money and prices still affects the role of monetary aggregates in the conduct of monetary policy. The stability of the money-price link depends ultimately on the properties of the demand-for-money relationship. This paper deals with the demand-for-money functions in individual EMU countries, whether such demand functions can be identified and, where identified, whether the functions are broadly similar in different countries. A change in the ECB interest rate should trigger the same change in the short-term interest rate in all EMU countries. As a consequence, the cost of borrowing would also change, which in turn would affect the demand for bank loans. The size of this resulting effect may vary from country to country, depending on the institutional setting, and could give rise to asymmetries in the monetary mechanism. The authors find significant differences in the interest rate semi-elasticities from country to country within the EMU, which, the authors argue, could pose serious problems in the conduct of the ECB' s common monetary policy.

OBJETIVO: Evaluar la idoneidad de las muestras de saliva para determinar la prevalencia de inmunidad a infecciones prevenibles mediante vacunación. MÉTODOS: Se obtuvieron muestras apareadas de sangre y saliva de 853 personas de todas las edades pertenecientes a una comunidad rural de Etiopía. Se cribó la saliva próxima a las encías para detectar anticuerpos específicos contra el sarampión y la rubéola, mediante técnicas de inmunosorción enzimática (ELISA) con captura potenciada de anticuerpos IgG (GAC), y anticuerpos anti-HBc, mediante un prototipo de GACELISA. Los anticuerpos IgG séricos contra el sarampión, la rubéola y HBc se determinaron mediante técnicas comerciales de ELISA. RESULTADOS: En comparación con el suero, la sensibilidad y especificidad de las pruebas realizadas con saliva fueron respectivamente las siguientes: 98% y 87% para el sarampión, 79% y 90% para la rubéola, y 43% y 87% para anti-HBc. Esas cifras arrojan unas estimaciones de la prevalencia poblacional a partir de la saliva de una precisión comparable a la conseguida con muestras de suero para el sarampión (todas las edades) y la rubéola (edad < 20 años). CONCLUSIÓN: Los resultados obtenidos parecen indicar que la saliva podría reemplazar al suero en los estudios de prevalencia de anticuerpos IgG. En futuras investigaciones deberá evaluarse la variación de los resultados de la prueba entre poblaciones, así como la disponibilidad de pruebas normalizadas de fácil uso.

OBJECTIF: Evaluer l’utilité des échantillons de sécrétions buccales pour déterminer la prévalence de l’immunité vis-à-vis d’infections évitables par la vaccination. MÉTHODS: Des échantillons appariés de sang et de sécrétions buccales ont été prélevés chez 853 personnes de tous âges dans une communauté rurale d’Ethiopie. Les échantillons de liquide gingival ont été soumis à une recherche des anticorps spécifiques de la rougeole et de la rubéole par titrage immuno-enzymatique (ELISA) avec capture d’IgG et amplification (GACELISA), et des anticorps anti-HBc au moyen d’un prototype de test GACELISA. Les IgG sériques vis-à-vis de la rougeole, de la rubéole et du HBc ont été déterminés à l’aide de tests ELISA du commerce. RÉSULTATS: Par rapport aux résultats obtenus avec le sérum, la sensibilité et la spécificité des titrages réalisés sur les sécrétions buccales étaient de 98% et 87% pour la rougeole, 79% et 90% pour la rubéole et 43% et 87% pour les anticorps anti-HBc. Ces caractéristiques ont permis d’obtenir avec les sécrétions buccales des estimations de la prévalence d’une précision égale à celle obtenue avec le sérum pour la rougeole (tous âges) et la rubéole (moins de 20 ans). CONCLUSION: Nos résultats indiquent que les sécrétions buccales pourraient remplacer le sérum dans les enquêtes sur la prévalence des IgG. Il faudra maintenant évaluer les différences de performance des titrages d’une population à l’autre et pouvoir disposer de tests normalisés faciles à utiliser.

OBJECTIVE: To assess the suitability of using oral-fluid samples for determining the prevalence of immunity to vaccine-preventable infections. METHODS: Paired blood and oral-fluid samples were obtained from 853 individuals of all ages from a rural Ethiopian community. Oral fluid around the gums was screened for measles- and rubella-specific antibodies using enhanced IgG antibody capture (GAC) enzyme-linked immunosorbent assays (ELISAs), and for anti-HBc antibodies using a prototype GACELISA. IgG antibodies in serum to measles, rubella and HBc were determined using commercial ELISAs. FINDINGS: Relative to serum, oral fluid assay sensitivity and specificity were as follows: 98% and 87% for measles, 79% and 90% for rubella, and 43% and 87% for anti-HBc. These assay characteristics yielded population prevalence estimates from oral fluid with a precision equal to that of serum for measles (all ages) and rubella (ages <20 years). CONCLUSION: Our results suggest that oral fluid could have the potential to replace serum in IgG antibody prevalence surveys. Further progress requires assessment of variation in assay performance between populations as well as the availability of standardized, easy to use assays.

OBJETIVO: investigar o transporte de alfa-tocoferol em lipoproteinas de coelhos sob dieta normal e durante sobrecarga de colesterol. DESENHO: Dois coelhos brancos da Nova Zelândia receberam 14C-alfa-tocoferol na forma de acetato em dose oral única e a recuperação de radioatividade nas lipoproteínas e plasma foi monitorizada. Lipoproteína de baixa densidade (LDL) destes animais foi obtida e marcada com [3H] ester de colesterol. Três outros coelhos receberam injeções desta LDL duplamente marcada na forma nativa, enquanto mais três animais receberam injeções desta LDL na forma acetilada. RESULTADOS: Queda dos níveis de 14C[3H] no plasma, captação hepática e níveis de radioatividade foram significativamente maior nos coelhos que receberam a forma acetilada de LDL. Partículas grandes de HDL, ricas em apolipoproteína E (apoE), continham níveis elevados de ambos os marcadores radioativos em coelhos que receberam injeção de acetil-LDL. CONCLUSÃO: Estes resultados sugerem a presença de mecanismos in vivo para o transporte reverso de alfa-tocoferol, análogo ao transporte reverso de colesterol.

OBJECTIVE: To investigate the transport of alpha-tocopherol in lipoproteins of rabbits under normal diet and under acute loading of cholesterol. DESIGN: Two New Zealand White rabbits were fed 14C-alpha-tocopherol acetate in a single oral dose and the recovery of radiolabel in lipoproteins and plasma was monitored. Low density lipoprotein (LDL) from these animals was obtained and labeled with [3H] cholesteryl ester. Three other rabbits were injected with this double-labeled LDL in the native form; while three other animals received this LDL in the acetylated form. RESULTS: Plasma clearance, liver uptake and levels of radiolabel in high density lipoprotein (HDL) of animals injected with 14C[3H]acetyl LDL were significantly higher than those in animals injected with 14C[3H]native LDL. Larger particles of HDL, rich in apolipoprotein E (apoE) carried significantly higher levels of both labels in rabbits injected with acetylated LDL. CONCLUSION: These results provide evidence for in vivo mechanisms of "reverse alpha-tocopherol transport", analogous to "reverse cholesterol transport".