Development of Multisector Alliances (MSAs): Organization and Leadership. ACES Working Papers, 2012

The research team reviewed numerous several multi- sectoral entities and identified nine GGNs that became the subject of our case studies. The research team conducted semi-structured interviews with executives and staff from each of these GNNs and prepared a profile, including a description of the unique evolution of the organization, goals and objectives, organizational structure and governance arrangements for each GGN. The following list provides an overview of the nine GGNs profiled: 1. Every Woman Every Child is an unprecedented global effort that mobilizes and amplifies action by governments, multilaterals, the private sector, research centers, academia and civil society to address life-threatening health challenges facing women and children globally. 2. HERproject catalyzes global partnerships and local Networks to improve female workers’ general and reproductive health in eight emerging economies. 3. R4 Rural Resilience Initiative is a cutting-edge, strategic, large-scale partnership between the public and private sectors to innovate and develop better tools to help the world’s most vulnerable people build resilient livelihoods. 4. Extractive Industry Transparency Initiative is a coalition of governments, companies, civil society groups, investors and international organizations that aims to improve transparency and accountability in the extractives sector. 5. Global Network for Neglected Tropical Diseases works with international partners at the highest level of government, business and society to break down the logistical and financial barriers to delivering existing treatments for the seven most common neglected tropical diseases. 6. Global Alliance for Improved Nutrition is an alliance that supports public-private partnerships to increase access to the missing nutrients in diets necessary for people, communities and economies to be stronger and healthier. 7. Inter-Agency Network For Education in Emergencies is a global Network of individuals and representatives from NGOs, United Nations and donor agencies, governments, academic institutions, schools and affected populations working to ensure all persons have the right to a quality and safe education in emergencies and post- crisis recovery. 8. mHealth Alliance works with diverse partners to advance mobile-based or mobile-enhanced solutions that deliver health through research, advocacy, support for the development of interoperable solutions and sustainable deployment models. 9. The Rainforest Alliance is a global non-profit that focuses on environmental conservation and sustainable development and works through collaborative partnerships with various stakeholders.

The curious absence of inter-municipal co-operation in England

In Europe local authorities often work with their neighbouring municipalities, whether to address a specific task or goal or through the course of regular policy making and implementation. In England, however, inter-municipal co-operation (IMC) is less common. Councils may work with service providers from the private and non-profit sectors but less often with neighbouring local authorities. Why this is the case may be explained by a number of historical and policy factors that often encourage councils to compete, rather than to work collaboratively with each other. The present government has encouraged councils to work in partnership with other organizations but there are few examples of increased horizontal cooperation between local authorities. Instead the prevailing model remains fixed on vertical co-working predicated on a principal-agent relationship between higher and lower tiers of government.

A versenyképesség társadalmi környezete

Kutatásunk alapvetése, hogy egy ország versenyképessége az értékteremtő munkamegosztást támogató teljes közösségi intézményrendszer sikeres működésén múlik. Munkánkkal arra kerestük a választ, milyen értékek és motivációk alakítják a magyar gazdaság intézményrendszerét. Nem a hivatalos magatartási szabályok statikus elemzésére koncentráltunk, hanem a normák, konvenciók és innovációk világára, az intézményrendszer jövőjét befolyásoló dinamikus elemekre. Elemzésünk fókuszában a társadalmi és vállalkozói értékek, a gazdaságpolitika formálók versenyképességi narratívái, a helyi gazdaságok versenyképességi tényezői, a versenyképesség javítását szolgáló magánkezdeményezések és a nonprofit szektor működése álltak. Fő eredményünk, hogy a Magyarország jövőbeli versenyképességét befolyásoló tudati elemek - a gazdasági döntéshozók motivációi és normái – megfelelő alapot teremtenek a gazdaságunk versenyképességét megerősítő üzleti, civil és kormányzati kezdeményezések számára. Magas közösségi és morális elvárások jellemzik a lakosság és a vállalkozók értékrendjét. A gazdaságpolitika-alkotók nyitottak az intézményi problémákra, a magyar véleményformálók körében egyetértés van a fő versenyképességi kihívásokat illetően. Jól azonosíthatóak a szervezők erőfeszítéseit kompenzálni képes versenyképességi összefogások keretei. A helyi gazdaságfejlesztés intézményei alakulóban vannak. A nonprofit szektor működési viszonyainak bizonytalansága ellenére a közcélúság és a versenyképesség közös területein (mint az atipikus foglalkoztatás) jól teljesít. Ezek az eredmények egyszerre nyitnak perspektívát a tudományos vizsgálódás és a gyakorlati cselekvés számára. Az önérdek és a közösségi értékteremtő képesség javításának motivációja közötti kapcsolat tudományos vizsgálata, a társadalmi innovációk kutatása a versenyképesség javíthatóságának kereteit tárhatja fel. Az üzleti, civil vagy kormányzati szereplők pedig akkor tudják a fogyasztói, közösségi elvárásokat sikeresen összeegyeztetni stratégiai céljaikkal, ha a gazdasági és társadalmi szereplők normáihoz, konvencióihoz igazítva alakítják ki intézményformáló stratégiáikat. __________ The competitiveness of nations is based on the successful function of the institutions that support the division of labor on value creation – this is the basic principle of this research. Our project investigates what values and motivations shape the institutional setting of Hungarian economy. We study the world of norms, conventions and innovations – the elements that shape the institutions. The static analysis of official rules has only a minor role in this approach. Research focuses (1) on the value system of entrepreneurs (2), on the mind setting of public managers and executives of economic policy (3) on the factors of local economic competitiveness, (4) on the actions of private and non-profit sector in order to enhance competitiveness. The main finding of this research is that the cognitive factors that shape the competitiveness of Hungary – the norms and motivations of decision makers in the economy – give a positive support for the competitiveness strengthening initiatives of business, non-profit and public sectors. The studies on the values system of entrepreneurs and citizens show that expectations and moral values connected to competitiveness are strong. The public managers of economic policy are open-minded and there is a general consensus of experts, business and politics on the key competitiveness challenges of Hungary. There are well defined frameworks to conceptualize the schemes that make organizers’ efforts affordable in private initiatives for competitiveness. There are various developments on the field of institutions for local economic development. The nonprofit sector has good results on the common fields of competiveness and equity (like atypical forms of employment) despite the uncertainties in the background of the sector. These results open perspectives both for scientific research and practical applications. The research on connection between individual goals and motivation to improve value creating ability of the society and the study of social innovation reveal new aspects of competitiveness. Business, non-profit or public leaders can better synchronize their strategies with the expectation of consumers, communities and constituencies if their intentions to shape institutional settings fit better to the norms and conventions of the social and economic stakeholders.

Performance in Private Clubs: Criteria Utilized by Managers

As the first step toward developing performance benchmarks for non profit private clubs, the authors identify the criteria that club managers use to evaluate club performance. Responses from 254 club managers across the US. indicate that all 16 performance criteria included in the survey were utilized to some extent, but the top three were membership satisfaction, quality of services offered, and quality of staff.

O processo de formulação do Programa Universidade para Todos: atores, coalizões e interesses

This thesis aims to analyze how the performance of the coalitions affected the formulation process of the Programa Universidade para Todos ─ Prouni. This is a program in which students from public high school, or who have been integral stock in private colleges and universities receive scholarships in private institutions, which receive tax incentives in federal taxes. As analytical framework, was used the advocacy coalition framework (ACF) framework developed by Sabatier and Jenkins-Smith (1993) that conceives the process of formulation of policies as a result of competition between groups of actors called coalitions, which are involved or interested in an issue of public policy. The actors coalesce into coalitions from beliefs, values, technical postures and positions on operational matters of public policy and act coordinately to defend their interests, interfering in the formulation of policies. With regard to methodological aspects, it is a qualitative study that used a narrative structure to present the development of Brazilian higher education and Prouni, analyzing official documents, shorthand notes of public congressional hearings and interviews with servers who worked in Ministry of Education (Brazil) time of program formulation, legislative counsel of the brazilian congress, plus the former deputy rapporteur of the Bill 3.582 / 2004, which led to Prouni. Two coalitions were identified: statist, which stood contrary to the program, and privatized, which defended its formulation. The clashes, which occurred mainly in Congress, highlight the strategies to operationalize beliefs. The two coalitions heavily used technical information and mobilization, through militancy (mobilizate troops). However, privatizing coalition acted more strongly in this case and was able to turn their beliefs into more effective action strategies. The final configuration of the Prouni was beneficial for private institutions, and showed a change in public policies related to higher education, since government support through tax breaks, before granted only to non-profit IES, became extensive also the IES with lucrative purpose.

Making it real of sustaining a fantasy? Personal budgets for older people

The restructuring of English social care services in the last three decades, as services are provided through a shifting collage of state, for-profit and non-profit organisations, exemplifies many of the themes of governance (Bevir, 2013). As well as institutional changes, there have been a new set of elite narratives about citizen behaviours and contributions, undergirded by modernist social science insights into the wellbeing benefits of ‘self-management’ (Mol, 2008). In this article, we particularly focus on the ways in which a narrative of personalisation has been deployed in older people’s social care services. Personalisation is based on an espoused aspiration of empowerment and autonomy through universal implementation to all users of social care (encapsulated in the Making it Real campaign [Think Local, Act Personal (TLAP), no date)], which leaves unproblematised the ever increasing residualisation of older adult social care and the abjection of the frail (Higgs and Gilleard, 2015). In this narrative of universal personalisation, older people are paradoxically positioned as ‘the unexceptional exception’; ‘unexceptional’ in the sense that, as the majority user group, they are rhetorically included in this promised transformation of adult social care; but ‘the exception’ in the sense that frail older adults are persistently placed beyond its reach. It is this paradoxical positioning of older adult social care users as the unexceptional exception and its ideological function that we seek to explain in this article.

Modelos de acompanhamento e controlo de natureza estratégica e o relato financeiro

Mestrado em Contabilidade Internacional

Estratégias de comunicação interna

Dissertação apresentada ao Instituto Superior de Contabilidade e Administração do Porto para obtenção do Grau de Mestre em Assessoria de Administração Orientada pela professora Arminda Sá Sequeira

Avaliação económica em transplantação renal : abordagem estratégica do processo de doação e análise de custo-utilidade do programa de transplantação renal versus hemodiálise

SUMÁRIO - O desafio atual da Saúde Pública é assegurar a sustentabilidade financeira do sistema de saúde. Em ambiente de recursos escassos, as análises económicas aplicadas à prestação dos cuidados de saúde são um contributo para a tomada de decisão que visa a maximização do bem-estar social sujeita a restrição orçamental. Portugal é um país com 10,6 milhões de habitantes (2011) com uma incidência e prevalência elevadas de doença renal crónica estadio 5 (DRC5), respetivamente, 234 doentes por milhão de habitantes (pmh) e 1.600 doentes/pmh. O crescimento de doenças associadas às causas de DRC, nomeadamente, diabetes Mellitus e hipertensão arterial, antecipam uma tendência para o aumento do número de doentes. Em 2011, dos 17.553 doentes em tratamento substitutivo renal, 59% encontrava-se em programa de hemodiálise (Hd) em centros de diálise extra-hospitalares, 37% viviam com um enxerto renal funcionante e 4% estavam em diálise peritoneal (SPN, 2011). A lista ativa para transplante (Tx) renal registava 2.500 doentes (SPN 2009). O Tx renal é a melhor modalidade terapêutica pela melhoria da sobrevida, qualidade de vida e relação custo-efetividade, mas a elegibilidade para Tx e a oferta de órgãos condicionam esta opção. Esta investigação desenvolveu-se em duas vertentes: i) determinar o rácio custo-utilidade incremental do Tx renal comparado com a Hd; ii) avaliar a capacidade máxima de dadores de cadáver em Portugal, as características e as causas de morte dos dadores potenciais a nível nacional, por hospital e por Gabinete Coordenador de Colheita e Transplantação (GCCT), e analisar o desempenho da rede de colheita de órgãos para Tx. Realizou-se um estudo observacional/não interventivo, prospetivo e analítico que incidiu sobre uma coorte de doentes em Hd que foi submetida a Tx renal. O tempo de seguimento mínimo foi de um ano e máximo de três anos. No início do estudo, colheram-se dados sociodemográficos e clínicos em 386 doentes em Hd, elegíveis para Tx renal. A qualidade de vida relacionada com a saúde (QVRS) foi avaliada nos doentes em Hd (tempo 0) e nos transplantados, aos três, seis, 12 meses, e depois, anualmente. Incluíram-se os doentes que por falência do enxerto renal transitaram para Hd. Na sua medição, utilizou-se um instrumento baseado em preferências da população, o EuroQol-5D, que permite o posterior cálculo dos QALY. Num grupo de 82 doentes, a QVRS em Hd foi avaliada em dois tempos de resposta o que permitiu a análise da sua evolução. Realizou-se uma análise custo-utilidade do Tx renal comparado com a Hd na perspetiva da sociedade. Identificaram-se os custos diretos, médicos e não médicos, e as alterações de produtividade em Hd e Tx renal. Incluíram-se os custos da colheita de órgãos, seleção dos candidatos a Tx renal e follow-up dos dadores vivos. Cada doente transplantado foi utilizado como controle de si próprio em diálise. Avaliou-se o custo médio anual em programa de Hd crónica relativo ao ano anterior à Tx renal. Os custos do Tx foram avaliados prospetivamente. Considerou-se como horizonte temporal o ciclo de vida nas duas modalidades. Usaram-se taxas de atualização de 0%, 3% e 5% na atualização dos custos e QALY e efetuaram-se análises de sensibilidade one way. Entre 2008 e 2010, 65 doentes foram submetidos a Tx renal. Registaram-se, prospetivamente, os resultados em saúde incluíndo os internamentos e os efeitos adversos da imunossupressão, e o consumo dos recursos em saúde. Utilizaram-se modelos de medidas repetidas na avaliação da evolução da QVRS e modelos de regressão múltipla na análise da associação da QVRS e dos custos do transplante com as características basais dos doentes e os eventos clínicos. Comparativamente à Hd, observou-se melhoria da utilidade ao 3º mês de Tx e a qualidade de vida aferida pela escala EQ-VAS melhorou em todos os tempos de observação após o Tx renal. O custo médio da Hd foi de 32.567,57€, considerado uniforme ao longo do tempo. O custo médio do Tx renal foi de 60.210,09€ no 1º ano e 12.956,77€ nos anos seguintes. O rácio custo-utilidade do Tx renal vs Hd crónica foi de 2.004,75€/QALY. A partir de uma sobrevivência do enxerto de dois anos e cinco meses, o Tx associou-se a poupança dos custos. Utilizaram-se os dados nacionais dos Grupos de Diagnóstico Homogéneos e realizou-se um estudo retrospectivo que abrangeu as mortes ocorridas em 34 hospitais com colheita de órgãos, em 2006. Considerou-se como dador potencial o indivíduo com idade entre 1-70 anos cuja morte ocorrera a nível hospitalar, e que apresentasse critérios de adequação à doação de rim. Analisou-se a associação dos dadores potenciais com características populacionais e hospitalares. O desempenho das organizações de colheita de órgãos foi avaliado pela taxa de conversão (rácio entre os dadores potenciais e efetivos) e pelo número de dadores potenciais por milhão de habitantes a nível nacional, regional e por Gabinete Coordenador de Colheita e Transplantação (GCCT). Identificaram-se 3.838 dadores potenciais dos quais 608 apresentaram códigos da Classificação Internacional de Doenças, 9.ª Revisão, Modificações Clínicas (CID- 9-MC) que, com maior frequência, evoluem para a morte cerebral. O modelo logit para dados agrupados identificou a idade, o rácio da lotação em Unidades de Cuidados Intensivos e lotação de agudos, existência de GCCT e de Unidade de Transplantação, e mortalidade por acidente de trabalho como fatores preditivos da conversão dum dador potencial em efetivo e através das estimativas do modelo logit quantificou-se a probabilidade dessa conversão. A doação de órgãos deve ser assumida como uma prioridade e as autoridades em saúde devem assegurar o financiamento dos hospitais com programas de doação, evitando o desperdício de órgãos para transplantação, enquanto um bem público e escasso. A colheita de órgãos deve ser considerada uma opção estratégica da atividade hospitalar orientada para a organização e planeamento de serviços que maximizem a conversão de dadores potenciais em efetivos incluindo esse critério como medida de qualidade e efetividade do desempenho hospitalar. Os resultados deste estudo demonstram que: 1) o Tx renal proporciona ganhos em saúde, aumento da sobrevida e qualidade de vida, e poupança de custos; 2) em Portugal, a taxa máxima de eficácia da conversão dos dadores cadavéricos em dadores potenciais está longe de ser atingida. O investimento na rede de colheita de órgãos para Tx é essencial para assegurar a sustentabilidade financeira e promover a qualidade, eficiência e equidade dos cuidados em saúde prestados na DRC5.

The system-wide impacts of the external benefits to higher education on the Scottish economy: An exploratory “micro-to-macro” approach

The private market benefits of education, i.e. the wage premia of graduates, are widely studied at the micro level, although the magnitude of their macroeconomic impact is disputed. However, there are additional benefits of education, which are less well understood but could potentially drive significant macroeconomic impacts. Following the taxonomy of McMahon (2009) we identify four different types of benefits of education. These are: private market benefits (wage premia); private non market benefits (own health, happiness, etc.); external market benefits (productivity spillovers; and external non-market benefits (crime rates, civic society, democratisation, etc.). Drawing on available microeconometric evidence we use a micro-to-macro simulation approach (Hermannsson et al, 2010) to estimate the macroeconomic impacts of external benefits of higher education. We explore four cases: technology spillovers from HEIs; productivity spillovers from more skilled workers in the labour market; reduction in property crime; and the potential overall impact of external and private non-market benefits. Our results suggest that the external economic benefits of higher education could potentially be very large. However, given the dearth of microeconomic evidence this result should be seen as tentative. Our aim is to illustrate the links from education to the wider economy in principle and encourage further research in the field.

Health care supply, payment system and medical practice : evidence from obstetric practice

ABSTRACTA significant share of deliveries are performed by Cesarian section (C-section) in Europe and in many developed and developing countries. The aims of this thesis are to highlight the non medical, especially economic and financial, incentives that explain the use of C-section, as well as the medical consequences of C-section on women's health, in regard with other factors of ob¬stetrical care quality such as hospital concentration. Those diagnoses enable us to exhibit ways of improvement of obstetrical care quality in France. Our analysis focus on two countries, France and Switzerland. In the first part of the thesis, we show the influence of two non medical factors on the C-section use, namely the hospital payment system on the one hand and the obstetricians behaviour, especially their demand for leisure, on the other hand. With French data on the year 2003, we show firstly that the fee-for-service payment system of private for profit hospitals induces a higher probability of using C-section. Obstetricians play also a preeminent role in the decision to use a C-section, as the probability of a C-section rises with the number of obstetricians. We then focus on a French reform introduced in 2004, to investigate the impact of Prospective Payment System on obstetric practise. We show that the rise of C-section rate between 2003 and 2006 is mainly caused by changes in hospitals and patients features. Obstetricians practises do not vary a lot for patients with the same risk code. In the mean time however, the number of women coded with a high risk rises. This can be caused by improvements in the quality of coding, obstetricians chosing codes that match better the real health state of their patients. Yet, it can also show that obstetricians change their coding practises to justify the use of certain practises, such as C-section, with no regard to the health state of patients. Financial factors are not the only non medical fac¬tors that can influence the resort to C-section. Using Shelton Brown ΠΙ identification strategy, we focus on the potential impact of obstetricians leisure preference on the use of C-section. We use the distributions of days and hours of delivering and the types of C-section - planned or emergency C-sections - to show that the obstetricians demand for leisure has a significant impact on the resort to C-section, but only in emergency situations. The second part of the thesis deals with some ways to improve obstetric care quality. We use on the one hand swiss and french data to study the impact of C-section on the patients' probability of having an obstetric complication and on the other hand the influence of hospital concentration on the quality of obstetric care. We find the same results as former medical studies about the risks entailed by C-section on obstetric complications.These results prove women ought to be better informed of the medical consequences of C-section and that the slowing of C-section use should be a priority of public health policy. We finally focus on another way to improve obstetric care quality, that is hospital lmarket concentration. We investigate the impact of hospital concentration by integrating the Herfindahl-Hirschman index in our model, on health care quality, measured by the HCUP indicator. We find that hospital concentration has a negative impact on obstetric care quality, which undermines today's policy of hospital closings in France.JEL classification: 112; 118Keywords: Hospital; C-section; Payment System; Counterfactual Estimation; Quality of Care.RÉSUMÉUne part importante des accouchements sont réalisés par césarienne en Europe et dans de nom¬breux pays développés ou en développement. Les objectifs de cette thèse sont de mettre en évidence les déterminants non médicaux, notamment économiques et financiers, expliquant le développe¬ment de cette pratique, ainsi que ses conséquences sur la santé des femmes après Γ accouchement, en lien avec d'autres facteurs comme la concentration locale des structures hospitalières. Les résul¬tats exposés dans cette thèse éclairent les perspectives et voies d'amélioration de la qualité des soins en obstétriques.Notre analyse se concentre sur deux pays : la France et la Suisse. Dans la première partie de la thèse, nous mettons en évidence l'influence de deux déterminants non médicaux sur l'emploi de la césarienne : le système de paiement des hôpitaux d'une part, et le comportement des médecins obstétriciens d'autre part. En étudiant des données françaises de 2003, nous montrons d'abord que le financement à l'acte des établissements privés engendre une hausse de la proba¬bilité de pratiquer une césarienne. Le rôle de l'obstrétricien paraît également déterminant dans la décision d'opérer une césarienne, la probabilité d'employer cette technique augmentant avec le nombre d'obstétriciens. Nous nous intéressons ensuite à l'impact de la mise en place en 2004 du système de paiement prospectif sur l'évolution des pratiques obstétricales entre 2003 et 2006 en France. La hausse du taux de recours à la césarienne entre 2004 et 2006 peut ainsi être principa¬lement imputée aux évolutions des caractéristiques des hôpitaux et des patients, les pratiques des obstétriciens, pour un même codage de la situation du patient, variant peu. Dans le même temps cependant, les pratiques de codage des patients parles obstétriciens évoluent fortement, les femmes étant de plus en plus nombreuses à porter des codes correspondant à des situations à risques. Cette évolution peut indiquer que la qualité du codage en 2006 s'est améliorée par rapport à 2004, le codage correspondant de plus en plus à la situation réelle des patientes. H peut aussi indiquer que les pratiques de codage évoluent pour justifier un recours accru à la césarienne, sans lien avec l'état réel des patientes. Les facteurs financiers ne sont pas les seuls facteurs non médicaux à pouvoir expliquer le recours à la césarienne : nous nous intéressons, en suivant la stratégie d'identifica¬tion de Shelton Brown m, à l'impact potentiel de la demande de loisir des médecins obstétriciens sur la pratique de la césarienne. En utilisant la distribution des jours et heures d'accouchement, et en distinguant les césariennes planifiées de celles effectuées en urgence, nous constatons que la demande de loisir des obstétriciens influence significativement le recours à la césarienne, mais uni¬quement pour les interventions d'urgence. La deuxième partie de la thèse est consacrée à l'étude de la qualité des soins en obstétriques. Nous utilisons des données suisses et françaises pour analyser d'une part l'impact de la césarienne sur la survenue de complications obstétricales et d'autre part l'impact de la concentration des soins sur la qualité des soins en obstétrique. Nons confirmons les résultats antérieurs de la littérature médicale sur la dangerosité de la césarienne comme facteur de complications obstétricales. Ces conclusions montrent que les femmes ont besoin d'être informées des conséquences de la césarienne sur leur santé et que le ralentissement de l'augmentation de la pratique de la césarienne devrait être un objectif de la politique publique de santé. Nous nous in¬téressons à un autre facteur d'amélioration des soins en obstrétique, l'organisation des hôpitaux et particulièrement leur concentration. Nous estimons ainsi l'effet de la concentration sur la qualité des soins obstétriques en intégrant l'indice de Herfindahl-Hirschman dans notre modèle, la qualité des soins étant mesurée à l'aide de l'indicateur HCUP. Nous constatons que la concentration des naissances a un impact négatif sur la qualité des soins en obstétrique, résultat qui va dans le sens contraire des politiques de fermeture d'hôpitaux menées actuellement en France. JEL classification : 112 ; 118Mots-clés : Hôpital ; Césarienne ; Système de paiement ; Contrefactuels ; Qualité des soins, sur la qualité des soins en obstétrique.

Variation in novel exons (RACEfrags) of the MECP2 gene in Rett syndrome patients and controls.

The study of transcription using genomic tiling arrays has lead to the identification of numerous additional exons. One example is the MECP2 gene on the X chromosome; using 5'RACE and RT-PCR in human tissues and cell lines, we have found more than 70 novel exons (RACEfrags) connecting to at least one annotated exon.. We sequenced all MECP2-connected exons and flanking sequences in 3 groups: 46 patients with the Rett syndrome and without mutations in the currently annotated exons of the MECP2 and CDKL5 genes; 32 patients with the Rett syndrome and identified mutations in the MECP2 gene; 100 control individuals from the same geoethnic group. Approximately 13 kb were sequenced per sample, (2.4 Mb of DNA resequencing). A total of 75 individuals had novel rare variants (mostly private variants) but no statistically significant difference was found among the 3 groups. These results suggest that variants in the newly discovered exons may not contribute to Rett syndrome. Interestingly however, there are about twice more variants in the novel exons than in the flanking sequences (44 vs. 21 for approximately 1.3 Mb sequenced for each class of sequences, p=0.0025). Thus the evolutionary forces that shape these novel exons may be different than those of neighboring sequences.

Guidelines for the clinical management of atrial fibrillation: a practical perspective.

Since the management of atrial fibrillation may be difficult in the individual patient, our purpose was to develop simple clinical recommendations to help the general internist manage this common clinical problem. Systematic review of the literature with evaluation of data-related evidence and framing of graded recommendations. Atrial fibrillation affects some 1% of the population in Western countries and is linked to a significant increase in morbidity and mortality. The management of atrial fibrillation requires individualised evaluation of the risks and benefits of therapeutic modalities, relying whenever possible on simple and validated tools. The two main points requiring a decision in clinical management are 1) whether or not to implement thromboembolic prevention therapy, and 2) whether preference should be given to a "rate control" or "rhythm control" strategy. Thromboembolic prophylaxis should be prescribed after individualised risk assessment: for patients at risk, oral anticoagulation with warfarin decreases the rate of embolic complications by 60% and aspirin by 20%, at the expense of an increased incidence of haemorrhagic complications. "Rate control" and "rhythm control" strategies are probably equivalent, and the choice should also be made on an individualised basis. To assist the physician in making his choices for the care of an atrial fibrillation patient we propose specific tables and algorithms, with graded recommendations. On the evidence of data from the literature we propose simple algorithms and tables for the clinical management of atrial fibrillation in the individual patient.

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials.

Impact of international consensus guidelines on antiviral therapy of chronic hepatitis C patients in Switzerland.

To assess the impact of international consensus conference guidelines on the attitude of Swiss specialists when facing the decision to treat chronic hepatitis C patients. Questionnaires focusing on the personal situation and treatment decisions were mailed to 165 patients who were newly diagnosed with hepatitis C virus (HCV) infection and enrolled into the Swiss Hepatitis C Cohort Study during the years 2002-2004. Survey respondents (n = 86, 52.1%) were comparable to non-respondents with respect to severity of liver disease, history of substance abuse and psychiatric co-morbidities. Seventy percent of survey respondents reported having been offered antiviral treatment. Patients deferred from treatment had less advanced liver fibrosis, were more frequently infected with HCV genotypes 1 or 4 and presented more often with a history of depression. There were no differences regarding age, socio-economic background, alcohol abuse, intravenous drug abuse or methadone treatment when compared with patients to whom treatment was proposed. Ninety percent of eligible patients agreed to undergo treatment. Overall, 54.6% of respondents and 78.3% of those considered eligible had actually received antiviral therapy by 2007. Ninety-five percent of patients reported high satisfaction with their own hepatitis C management. Consistent with latest international consensus guidelines, patients enrolled in the Swiss Hepatitis C Cohort with a history of substance abuse were not withheld antiviral treatment. A multidisciplinary approach is warranted to provide antiviral treatment to patients suffering from depression.