Frequência e significado clínico da expressão da glicoproteína P e da proteína relacionada a resistência a múltiplas drogas na leucemia mielóide aguda

Despite the advances in the cure rate for acute myeloid leukemia, a considerable number of patients die from their disease due to the occurrence of multidrug resistance (MDR). Overexpression of the transporter proteins P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) confer resistance to the treatment these leukemias. OBJECTIVE: To analyze the expression of the Gpp and MRP1 in patients with AML by flow cytometry (FC) and to determine the correlation between expression and demographic and also clinical and laboratorial variables. METHODS: Bone marrow and peripheral blood samples from 346 patients with a diagnosis of AML were assessed for the expression of Pgp and MRP1 by FC. RESULTS: The expression of Pgp and MRP1 was found in 111 (32.1%) and 133 (38.4%) patients, respectively, with greater prevalence in older patients and lower in adolescents, observing also a high incidence in patients with refractory disease, recurrence and secondary in comparison with the cases of de novo AML. Regarding the laboratory findings, we observed a higher correlation statistically significant between the expression of Pgp and MRP1 in AML CD34+ and FAB AML M7, M5A and M2 and lower the M3 subtype, not observed statistically significant correlation between the phenotype MDR and other laboratory data such with hemoglobin, leukocyte count, platelet count, aberrant expression of lymphoid antigens (CD2, CD7 and CD19) and clinical signs related to the disease. CONCLUSIONS: The results showed that the detection of MDR phenotype by flow cytometry can be a molecular marker for prognosis independent patients diagnosed with AML.

Challenges in the Management of Geriatric Obesity in High Risk Populations.

The global prevalence of obesity in the older adult population is growing, an increasing concern in both the developed and developing countries of the world. The study of geriatric obesity and its management is a relatively new area of research, especially pertaining to those with elevated health risks. This review characterizes the state of science for this "fat and frail" population and identifies the many gaps in knowledge where future study is urgently needed. In community dwelling older adults, opportunities to improve both body weight and nutritional status are hampered by inadequate programs to identify and treat obesity, but where support programs exist, there are proven benefits. Nutritional status of the hospitalized older adult should be optimized to overcome the stressors of chronic disease, acute illness, and/or surgery. The least restrictive diets tailored to individual preferences while meeting each patient's nutritional needs will facilitate the energy required for mobility, respiratory sufficiency, immunocompentence, and wound healing. Complications of care due to obesity in the nursing home setting, especially in those with advanced physical and mental disabilities, are becoming more ubiquitous; in almost all of these situations, weight stability is advocated, as some evidence links weight loss with increased mortality. High quality interdisciplinary studies in a variety of settings are needed to identify standards of care and effective treatments for the most vulnerable obese older adults.

Perioperative cerebrospinal fluid and plasma inflammatory markers after orthopedic surgery.

BACKGROUND: Postoperative delirium is prevalent in older patients and associated with worse outcomes. Recent data in animal studies demonstrate increases in inflammatory markers in plasma and cerebrospinal fluid (CSF) even after aseptic surgery, suggesting that inflammation of the central nervous system may be part of the pathogenesis of postoperative cognitive changes. We investigated the hypothesis that neuroinflammation was an important cause for postoperative delirium and cognitive dysfunction after major non-cardiac surgery. METHODS: After Institutional Review Board approval and informed consent, we recruited patients undergoing major knee surgery who received spinal anesthesia and femoral nerve block with intravenous sedation. All patients had an indwelling spinal catheter placed at the time of spinal anesthesia that was left in place for up to 24 h. Plasma and CSF samples were collected preoperatively and at 3, 6, and 18 h postoperatively. Cytokine levels were measured using ELISA and Luminex. Postoperative delirium was determined using the confusion assessment method, and cognitive dysfunction was measured using validated cognitive tests (word list, verbal fluency test, digit symbol test). RESULTS: Ten patients with complete datasets were included. One patient developed postoperative delirium, and six patients developed postoperative cognitive dysfunction. Postoperatively, at different time points, statistically significant changes compared to baseline were present in IL-5, IL-6, I-8, IL-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, IL-6/IL-10, and receptor for advanced glycation end products in plasma and in IFN-γ, IL-6, IL-8, IL-10, MCP-1, MIP-1α, MIP-1β, IL-8/IL-10, and TNF-α in CSF. CONCLUSIONS: Substantial pro- and anti-inflammatory activity in the central neural system after surgery was found. If confirmed by larger studies, persistent changes in cytokine levels may serve as biomarkers for novel clinical trials.

Tooth replacement for partially dentate elders: a willingness-to-pay analysis

Objectives: The primary aim of this study was to investigate partially dentate elders' willingness-to-pay (WTP) for two different tooth replacement strategies: Removable Partial Dentures (RPDs) and, functionally orientated treatment according to the principles of the Shortened Dental Arch (SDA). The secondary aim was to measure the same patient groups' WTP for dental implant treatment.Methods: 55 patients who had completed a previous RCT comparing two tooth replacement strategies (RPDs (n=27) and SDA (n=28)) were recruited (Trial Registration no. ISRCTN26302774). Patients were asked to indicate their WTP for treatment to replace missing teeth in a number of hypothetical scenarios using the payment card method of contingency evaluation coupled to different costs. Data were collected on patients' social class, income levels and other social circumstances. A Mann-Whitney U Test was used to compare differences in WTP between the two treatment groups. To investigate predictive factors for WTP, multiple linear regression analyses were conducted.Results: The median age for the patient sample was 72.0 years (IQR: 71-75 years). Patients who had been provided with RPDs indicated that their WTP for this treatment strategy was significantly higher (€550; IQR: 500-650) than those patients who had received SDA treatment (€500; IQR: 450-550) (p=0.003). However patients provided with RPDs indicated that their WTP for SDA treatment (€650; IQR: 600-650) was also significantly higher than those patients who had actually received functionally orientated treatment (€550; IQR: 500-600) (p<0.001). The results indicated that both current income levels and previous treatment allocation were significantly correlated to WTP for both the RPD and the SDA groups. Patients in both treatment groups exhibited little WTP for dental implant treatment with a median value recorded which was half the market value for this treatment (€1000; IQR: 500-1000).Conclusions: Amongst this patient cohort previous treatment experience had a strong influence on WTP as did current income levels. Both treatment groups indicated a very strong WTP for simpler, functionally orientated care using adhesive fixed prostheses (SDA) over conventional RPDs. Clinical significance: Partially dentate older patients expressed a strong preference for functionally orientated tooth replacement as an alternative to conventional RPDs.

Survenue des arythmies et troubles de conduction après un remplacement de la valve aortique par cathéter : incidence et impact

La sténose aortique est la cardiopathie valvulaire la plus fréquente retrouvée chez les patients agés. Suite à l’apparition des symptômes, la survie des patients diminue de façon drastique en l’absence d’un remplacement valvulaire aortique. Cependant, une proportion considérable de ces patients n’est pas opérée en raison d’un risque chirurgical élevé, l’âge étant l’une des principales raisons de refus d’un remplacement valvulaire aortique chirurgical. Ce défaut dans la prise en charge des ces patients a favorisé le développement du remplacement valvulaire aortique par cathéter où implantation valvulaire aortique par cathèter (TAVR ou TAVI), qui a représenté une révolution dans le traitement de la sténose aortique. Cette intervention est actuellement un traitement de routine chez les patients à haut risque chirurgical atteints d’une sténose aortique, même si la chirurgie cardiaque n’est pas contre-indiquée. Ces dernières années ont vu un changement de profil des candidats potentiels vers une population à plus faible risque. Cependant, plusieurs préoccupations demeurent. L’une des plus importantes est la survenue des arythmies et de troubles de conduction, notamment le bloc de branche gauche et le bloc auriculo-ventriculaire, qui sont des complications fréquemment associées au TAVR. Malgré l’évolution de la technologie et le développement de nouveaux dispositifs réduisant le taux global de complications, aucune amélioration n’a pas été intégrée pour prévenir l’apparition de telles complications. De plus, l’utilisation de certains dispositifs de nouvelle génération semble être associée à un risque accru de troubles de conduction, et par conséquent, l’incidence de ces complications pourrait augmenter dans le futur. Cependant, L’impact et l’évolution de ces complications sont inconnus. Ce travail de recherche évalue l’incidence et l’évolution des troubles de conduction suite au TAVR et l’impact des blocs de branche gauche de novo et de l’implantation d’un pacemaker sur les résultats cliniques et échocardiographiques.

Heart failure in young adults

Heart failure (HF) is a major health concern affecting 15 million people in Europe and around 900 000 people in the U.K. HF predominantly affects the elderly, with the mean age of patients with a diagnosis of HF between 70 and 80 years. Most previous HF studies have accordingly focused on older patients. Although HF is less common in younger adults (<65 years), 15% to 20% of patients hospitalised with HF are younger than 60 years of age. Very few studies have described the characteristics of younger adults with HF and its outcome. The aims of this thesis are to describe the clinical characteristics of younger adults with HF, explore the epidemiology of HF in younger adults and determine their short- and long-term outcomes. This was made possible by access multiple databases consisting of large patient cohorts with HF. The first chapter is a systematic literature review of younger adults with HF. Gaps in the current literature were identified and the thesis focused on some of these. The CHARM study allows detail characterisations of younger adults with HF. It recorded characteristics of patients with HF, including symptoms and signs of HF, electrocardiographic changes, chest radiographic findings, and also left ventricular ejection fraction. HF hospitalisations and its precipitating factors were also recorded systematically. Younger adults were more likely to have a third heart sound and hepatomegaly, but less likely to have pulmonary crackles and peripheral oedema. Similarly, radiological findings in younger adults were less likely to show interstitial pulmonary oedema or pleural effusion. Interestingly, younger adults aged <40 years not only have similar HF hospitalisation rate to older patients, however during their presentation with decompensated HF, they were less likely to have clinical pulmonary oedema and radiological signs of HF. Physicians managing younger adults with HF need to be aware of this. Younger adults were also less compliant with medications and lifestyle restriction resulting in hospitalisation with decompensated HF. Fortunately, despite these challenges, mortality rates in younger adults with HF were lower compared to older patients. To further substantiate the findings from the CHARM study, the MAGGIC study, a meta-analysis consists of over 40 000 patients with HF from large observational studies and randomised controlled trials, was examined. In both databases, the commonest aetiology of HF in younger adults was dilated cardiomyopathy. The ejection fraction was the lowest in younger adults. Similar to the CHARM study, mortality rates in younger adults were lower compared to older patients. However, in the MAGGIC study, by stratifying mortality into patients with preserved ejection fraction and with reduced ejection fraction, younger patients with preserved ejection fraction have a much lower mortality rate compared to patients with reduced ejection fraction. Findings from clinical trials are not always reflective of the real life clinical practice. The U.K. Clinical Practice Research Datalink (CPRD), a large and well-validated primary care database with 654 practices contributing information into the database representing approximated 8% of the U.K. population, is a rich dataset offering a unique opportunity to examine the characteristics, treatments, and outcomes of younger adults with HF in the community. In contrast to the CHARM and MAGGIC studies, younger adults aged <40 years were stratified into 20-29 and 30-39 years in the CPRD analysis. This is possible due to the larger number of younger adults with HF. Further stratifying the younger age groups demonstrated heterogeneity among younger adults with HF. In contrast to previous data showing younger adults have lower co-morbidities, the proportions of depression, chronic kidney disease, asthma, and any connective tissue disease were high among patients aged 20-29 years in the analysis from the CPRD. Surprisingly, the treatment rates for angiotensin converting enzyme (ACE) inhibitor, and aldosterone antagonist were the lowest in patients aged 20-29 years. With the exception of patients aged ≥80 years, treatment rate with beta-blocker was also the lowest in patients aged 20-29 years. With over two decades of follow up, long-term mortality rates in younger adults with HF can be determined. The mortality rates continued to decline from 1988 to 2011. Physicians managing younger adults with HF can now use this contemporary data to provide prognostic information to patients and their family. A hospital administrative database is the logical next platform to explore younger adults with HF. The Alberta Ministry of Health database links an outpatient database to a hospitalisation database providing ample data to examine the relationship between outpatient clinic visits and hospital admissions in younger adults with HF. Following a diagnosis of HF in the outpatient setting, younger adults were admitted to the hospital with decompensated HF much sooner than older patients. Younger adults also presented to emergency department more frequently following their first hospitalisation for HF. In conclusion, this thesis presented the characteristics and outcomes of younger adults with HF, and helped to extend our current understanding on this important topic. I hope the data presented here will benefit not only physicians looking after younger adults with HF, but also patients and their family.

Étude S.AGES : recueil et suivi de nouveaux cas de syndromes d’apnées obstructives au cours du sommeil (SAOS), chez des sujets âgés de plus de 70 ans, diagnostiqués dans les structures de pneumologie et de gériatrie

International audience

Programa Nacional de Vigilância da Gripe: relatório da época 2015/2016

O vírus da gripe é uma das maiores causas de morbilidade e mortalidade em todo o mundo, afetando um elevado número de indivíduos em cada ano. Em Portugal a vigilância epidemiológica da gripe é assegurada pelo Programa Nacional de Vigilância da Gripe (PNVG), através da integração da informação das componentes clínica e virológica, gerando informação detalhada relativamente à atividade gripal. A componente clínica é suportada pela Rede Médicos-Sentinela e tem um papel especialmente relevante por possibilitar o cálculo de taxas de incidência permitindo descrever a intensidade e evolução da epidemia de gripe. A componente virológica tem por base o diagnóstico laboratorial do vírus da gripe e tem como objetivos a deteção e caraterização dos vírus da gripe em circulação. Para o estudo mais completo da etiologia da síndrome gripal foi efectuado o diagnóstico diferencial de outros vírus respiratórios: vírus sincicial respiratório tipo A (RSV A) e B (RSV B), o rhinovírus humano (hRV), o vírus parainfluenza humano tipo 1 (PIV1), 2 (PIV2) e 3 (PIV3), o coronavírus humano (hCoV), o adenovírus (AdV) e o metapneumovirus humano (hMPV). Desde 2009 a vigilância da gripe conta também com a Rede Portuguesa de Laboratórios para o Diagnóstico da Gripe que atualmente é constituída por 15 hospitais onde se realiza o diagnóstico laboratorial da gripe. A informação obtida nesta Rede Laboratorial adiciona ao PNVG dados relativos a casos de doença respiratória mais severa com necessidade de internamento. Em 2011/2012, foi lançado um estudo piloto para vigiar os casos graves de gripe admitidos em Unidades de Cuidados Intensivos (UCI) que deu origem à atual Rede de vigilância da gripe em UCI constituída em 2015/2016 por 31 UCI (324 camas). Esta componente tem como objetivo a monitorização de novos casos de gripe confirmados laboratorialmente e admitidos em UCI, permitindo a avaliação da gravidade da doença associada à infeção pelo vírus da gripe. O Sistema da Vigilância Diária da Mortalidade constitui uma componente do PNVG que permite monitorizar a mortalidade semanal por “todas as causas” durante a época de gripe. É um sistema de vigilância epidemiológica que pretende detetar e estimar de forma rápida os impactos de eventos ambientais ou epidémicos relacionados com excessos de mortalidade. A notificação de casos de Síndrome Gripal (SG) e a colheita de amostras biológicas foi realizada em diferentes redes participantes do PNVG: Rede de Médicos-Sentinela, Rede de Serviços de Urgência/Obstetrícia, médicos do Projeto EuroEVA, Rede Portuguesa de Laboratórios para o Diagnóstico da Gripe e Rede vigilância da gripe em UCI. Na época de vigilância da gripe de 2015/2016 foram notificados 1.273 casos de SG, 87% dos quais acompanhados de um exsudado da nasofaringe para diagnóstico laboratorial. No inverno de 2015/2016 observou-se uma atividade gripal de baixa intensidade. O período epidémico ocorreu entre a semana 53/2015 e a semana 8/2016 e o valor mais elevado da taxa de incidência semanal de SG (72,0/100000) foi observado na semana 53/2015. De acordo com os casos notificados à Rede Médicos-Sentinela, o grupo etário dos 15 aos 64 anos foi o que apresentou uma incidência cumulativa mais elevada. O vírus da gripe foi detetado em 41,0% dos exsudados da nasofaringe recebidos tendo sido detetados outros vírus respiratórios em 24% destes. O vírus da gripe A(H1)pdm09 foi o predominantemente detetado em 90,4% dos casos de gripe. Foram também detetados outros vírus da gripe, o vírus B - linhagem Victoria (8%), o vírus A(H3) (1,3%) e o vírus B- linhagem Yamagata (0,5%). A análise antigénica dos vírus da gripe A(H1)pdm09 mostrou a sua semelhança com a estirpe vacinal 2015/2016 (A/California/7/2009), a maioria dos vírus pertencem ao novo grupo genético 6B.1, que foi o predominantemente detetado em circulação na Europa. Os vírus do tipo B apesar de detetados em número bastante mais reduzido comparativamente com o subtipo A(H1)pdm09, foram na sua maioria da linhagem Victoria que antigenicamente se distinguem da estirpe vacinal de 2015/2016 (B/Phuket/3073/2013). Esta situação foi igualmente verificada nos restantes países da Europa, Estados Unidos da América e Canadá. Os vírus do subtipo A(H3) assemelham-se antigenicamente à estirpe selecionada para a vacina de 2016/2017 (A/Hong Kong/4801/2014). Geneticamente a maioria dos vírus caraterizados pertencem ao grupo 3C.2a, e são semelhantes à estirpe vacinal para a época de 2016/2017. A avaliação da resistência aos antivirais inibidores da neuraminidase, não revelou a circulação de estirpes com diminuição da suscetibilidade aos inibidores da neuraminidase (oseltamivir e zanamivir). A situação verificada em Portugal é semelhante à observada a nível europeu. A percentagem mais elevada de casos de gripe foi verificada nos indivíduos com idade inferior a 45 anos. A febre, as cefaleias, o mal-estar geral, as mialgias, a tosse e os calafrios mostraram apresentar uma forte associação à confirmação laboratorial de um caso de gripe. Foi nos doentes com imunodeficiência congénita ou adquirida que a proporção de casos de gripe foi mais elevada, seguidos dos doentes com diabetes e obesidade. A percentagem total de casos de gripe em mulheres grávidas foi semelhante à observada nas mulheres em idade fértil não grávidas. No entanto, o vírus da gripe do tipo A(H1)pdm09 foi detetado em maior proporção nas mulheres grávidas quando comparado as mulheres não grávidas. A vacina como a principal forma de prevenção da gripe é especialmente recomendada em indivíduos com idade igual ou superior a 65 anos, doentes crónicos e imunodeprimidos, grávidas e profissionais de saúde. A vacinação antigripal foi referida em 13% dos casos notificados. A deteção do vírus da gripe ocorreu em 25% dos casos vacinados e sujeitos a diagnóstico laboratorial estando essencialmente associados ao vírus da gripe A(H1)pdm09, o predominante na época de 2015/2016. Esta situação foi mais frequentemente verificada em indivíduos com idade compreendida entre os 15 e 45 anos. A confirmação de gripe em indivíduos vacinados poderá estar relacionada com uma moderada efetividade da vacina antigripal na população em geral. A informação relativa à terapêutica antiviral foi indicada em 67% casos de SG notificados, proporção superior ao verificado em anos anteriores. Os antivirais foram prescritos a um número reduzido de doentes (9,0%) dos quais 45.0% referiam pelo menos a presença de uma doença crónica ou gravidez. O antiviral mais prescrito foi o oseltamivir. A pesquisa de outros vírus respiratórios nos casos de SG negativos para o vírus da gripe, veio revelar a circulação e o envolvimento de outros agentes virais respiratórios em casos de SG. Os vírus respiratórios foram detetados durante todo o período de vigilância da gripe, entre a semana 40/2015 e a semana 20/2016. O hRV, o hCoV e o RSV foram os agentes mais frequentemente detetados, para além do vírus da gripe, estando o RSV essencialmente associado a crianças com idade inferior a 4 anos de idade e o hRV e o hCoV aos adultos e população mais idosa (≥ 65 anos). A Rede Portuguesa de Laboratórios para o Diagnóstico da Gripe, efetuou o diagnóstico da gripe em 7443 casos de infeção respiratória sendo o vírus da gripe detetado em 1458 destes casos. Em 71% dos casos de gripe foi detetado o vírus da gripe A(H1)pdm09. Os vírus da gripe do tipo A(H3) foram detetados esporadicamente e em número muito reduzido (2%), e em 11% o vírus da gripe A (não subtipado). O vírus da gripe do tipo B foi detetado em 16% dos casos. A frequência de cada tipo e subtipo do vírus da gripe identificados na Rede Hospitalar assemelha-se ao observado nos cuidados de saúde primários (Rede Médicos-Sentinela e Serviços de Urgência). Foi nos indivíduos adultos, entre os 45-64 anos, que o vírus A(H1)pdm09 representou uma maior proporção dos casos de gripe incluindo igualmente a maior proporção de doentes que necessitaram de internamento hospitalar em unidades de cuidados intensivos. O vírus da gripe do tipo B esteve associado a casos de gripe confirmados nas crianças entre os 5 e 14 anos. Outros vírus respiratórios foram igualmente detetados sendo o RSV e os picornavírus (hRV, hEV e picornavírus) os mais frequentes e em co circulação com o vírus da gripe. Durante a época de vigilância da gripe, 2015/2016, não se observaram excessos de mortalidade semanais. Nas UCI verificou-se uma franca dominância do vírus da gripe A(H1)pdm09 (90%) e a circulação simultânea do vírus da gripe B (3%). A taxa de admissão em UCI oscilou entre 5,8% e 4,7% entre as semanas 53 e 12 tendo o valor máximo sido registado na semana 8 de 2016 (8,1%). Cerca de metade dos doentes tinha entre 45 e 64 anos. Os mais idosos (65+ anos) foram apenas 20% dos casos, o que não será de estranhar, considerando que o vírus da gripe A(H1)pdm09 circulou como vírus dominante. Aproximadamente 70% dos doentes tinham doença crónica subjacente, tendo a obesidade sido a mais frequente (37%). Comparativamente com a pandemia, em que circulou também o A(H1)pdm09, a obesidade, em 2015/2016, foi cerca de 4 vezes mais frequente (9,8%). Apenas 8% dos doentes tinha feito a vacina contra a gripe sazonal, apesar de mais de 70% ter doença crónica subjacente e de haver recomendações da DGS nesse sentido. A taxa de letalidade foi estimada em 29,3%, mais elevada do que na época anterior (23,7%). Cerca de 80% dos óbitos ocorreram em indivíduos com doença crónica subjacente que poderá ter agravado o quadro e contribuído para o óbito. Salienta-se a ausência de dados históricos publicados sobre letalidade em UCI, para comparação. Note-se que esta estimativa se refere a óbitos ocorridos apenas durante a hospitalização na UCI e que poderão ter ocorrido mais óbitos após a alta da UCI para outros serviços/enfermarias. Este sistema de vigilância da gripe sazonal em UCI poderá ser aperfeiçoado nas próximas épocas reduzindo a subnotificação e melhorando o preenchimento dos campos necessários ao estudo da doença. A época de vigilância da gripe 2015/2016 foi em muitas caraterísticas comparável ao descrito na maioria dos países europeus. A situação em Portugal destacou-se pela baixa intensidade da atividade gripal, pelo predomínio do vírus da gripe do subtipo A(H1)pdm09 acompanhada pela deteção de vírus do tipo B (linhagem Victoria) essencialmente no final da época gripal. A mortalidade por todas as causas durante a epidemia da gripe manteve-se dentro do esperado, não tendo sido observados excessos de mortalidade. Os vírus da gripe do subtipo predominante na época 2015/2016, A(H1)pdm09, revelaram-se antigénicamente semelhantes à estirpe vacinal. Os vírus da gripe do tipo B detetados distinguem-se da estirpe vacinal de 2015/2016. Este facto conduziu à atualização da composição da vacina antigripal para a época 2016/2017. A monitorização contínua da epidemia da gripe a nível nacional e mundial permite a cada inverno avaliar o impacto da gripe na saúde da população, monitorizar a evolução dos vírus da gripe e atuar de forma a prevenir e implementar medidas eficazes de tratamento da doença, especialmente quando esta se apresenta acompanhada de complicações graves.

Studies of antihypertensive drug persistence and adherence in the Glasgow Blood Pressure Clinic

Hypertension (HTN) is a major risk factor for cardiovascular diseases including stroke, coronary heart disease (CHD), chronic renal failure, peripheral vascular disease, myocardial infarction, congestive heart failure and premature death. The prevalence of HTN in Scotland is very high and although a high proportion of the patients receive antihypertensive medications, blood pressure (BP) control is very low. Recommendations for starting a specific antihypertensive class have been debated between various guidelines over the years. Some guidelines and HTN studies have preferred to start with a combination of an antihypertensive class instead of using a single therapy, and they have found greater BP reductions with combination therapies than with monotherapy. However, it has been shown in several clinical trials that 20% to 35% of hypertensive patients could not achieve the target BP, even though they received more than three antihypertensive medications. Several factors were found to affect BP control. Adherence and persistence were considered as the factors contributing the most to uncontrolled hypertension. Other factors such as age, sex, body mass index (BMI), alcohol intake, baseline systolic BP (SBP), and the communication between physicians and patients have been shown to be associated with uncontrolled BP and resistant hypertension. Persistence, adherence and compliance are interchangeable terms and have been used in the literature to describe a patient’s behaviour with their antihypertensive drugs and prescriptions. The methods used to determine persistence and adherence, as well as the inclusion and exclusion criteria, vary between persistence and adherence studies. The prevalence of persistence and adherence have varied between these studies, and were determined to be high in some studies and low in others. The initiation of a specific antihypertensive class has frequently been associated with an increase or decrease in adherence and persistence. The tolerability and efficacy of the initial antihypertensive class have been the most common methods of explaining this association. There are also many factors that suggest a relationship with adherence and persistence. Some factors in previous studies, such as age, were frequently associated with adherence and persistence. On the other hand, relationships with certain factors have varied between the studies. The associations of age, sex, alcohol use, smoking, baseline systolic blood pressure (SBP) and diastolic BP (DBP), the presence of comorbidities, an increase in the number of pills and the relationship between patients and physicians with adherence and persistence have been the most commonly investigated factors. Most studies have defined persistence in terms of a patient still taking medication after a period of time. A medication possession ratio (MPR) ≥ 80 has been used to define compliance. Either of these terminologies, or both, have been used to estimate adherence. In this study, I used the same definition for persistence to identify patients who have continued with their initial treatment, and used persistence and MPR to define patients who adhered to their initial treatment. The aim of this study was to estimate the prevalence of persistence and adherence in Scotland. Also, factors that could have had an effect on persistence and adherence were studied. The number of antihypertensive drugs taken by patients during the study and factors that led to an increase in patients being on a combination therapy were also evaluated. The prevalence of resistance and BP control were determined by taking the BP after the last drug had been taken by persistent patients during five follow-up studies. The relationship of factors such as age, sex, BMI, alcohol use, smoking, estimated glomerular filtration rate (eGFR), and albumin levels with BP reductions for each antihypertensive class were determined. Information Services Division (ISD) data, which includes all antihypertensive drugs, were collected from pharmacies in Scotland and linked to the Glasgow Blood Pressure Clinic (GBPC) database. This database also includes demographic characteristics, BP readings and clinical results for all patients attending the GBPC. The case notes for patients who attended the GBPC were reviewed and all new antihypertensive drugs that were prescribed between visits, BP before and after taking drugs, and any changes in the hypertensive drugs were recorded. A total of 4,232 hypertensive patients were included in the first study. The first study showed that angiotensin converting enzyme inhibitor (ACEI) and beta-blockers (BB) were the most prescribed antihypertensive classes between 2004 and 2013. Calcium channel blockers (CCB), thiazide diuretics and angiotensin receptor blockers (ARB) followed ACEI and BB as the most prescribed drugs during the same period. The prescription trend of the antihypertensive class has changed over the years with an increase in prescriptions for ACEI and ARB and a decrease in prescriptions for BB and diuretics. I observed a difference in antihypertensive class prescriptions by age, sex, SBP and BMI. For example, CCB, thiazide diuretics and alpha-blockers were more likely to be prescribed to older patients, while ACEI, ARB or BB were more commonly prescribed for younger patients. In a second study, 4,232 and 3,149 hypertensive patients were included to investigate the prevalence of persistence in the Scottish population in 1- and 5-year studies, respectively. The prevalence of persistence in the 1-year study was 72.9%, while it was only 62.8% in the 5-year study. Those patients taking ARB and ACEI showed high rates of persistence and those taking diuretics and alpha blockers had low rates of persistence. The association of persistence with clinical characteristics was also investigated. Younger patients were more likely to totally stop their treatment before restarting their treatment with other antihypertensive drugs. Furthermore, patients who had high SBP tended to be non-persistent. In a third study, 3,085 and 1,979 patients who persisted with their treatment were included. In the first part of the study, MPR was calculated, and patients with an MPR ≥ 80 were considered as adherent. Adherence rates were 29.9% and 23.4% in the 1- and 5-year studies, respectively. Patients who initiated the study with ACEI were more likely to adhere to their treatments. However, patients who initiated the study with thiazide diuretics were less likely to adhere to their treatments. Sex, age and BMI were different between the adherence and non-adherence groups. Age was an independent factor affecting adherence rates during both the 1- and 5-year studies with older patients being more likely to be adherent. In the second part of the study, pharmacy databases were checked with patients' case notes to compare antihypertensive drugs that were collected from the pharmacy with the antihypertensive prescription given during the patient’s clinical visit. While 78.6% of the antihypertensive drugs were collected between clinical visits, 21.4% were not collected. Patients who had more days to see the doctor in the subsequent visit were more likely to not collect their prescriptions. In a fourth study, 3,085 and 1,979 persistent patients were included to calculate the number of antihypertensive classes that were added to the initial drug during the 1-year and 5-year studies, respectively. Patients who continued with treatment as a monotherapy and who needed a combination therapy were investigated during the 1- and 5-year studies. In all, 55.8% used antihypertensive drugs as a monotherapy and 44.2% used them as a combination therapy during the 1-year study. While 28.2% of patients continued with treatment without the required additional therapy, 71.8% of the patients needed additional therapy. In all, 20.8% and 46.5% of patients required three different antihypertensive classes or more during the 1-year and 5-year studies, respectively. Patients who started with ACEI, ARB and BB were more likely to continue as monotherapy and less likely to need two more antihypertensive drugs compared with those who started with alpha-blockers, non-thiazide diuretics and CCB. Older ages, high BMI levels, high SBP and high alcohol intake were independent factors that led to an increase in the probability of patients taking combination therapies. In the first part of the final study, BPs were recorded after the last drug had been taken during the 5 year study. There were 815 persistent patients who were assigned for this purpose. Of these, 39% had taken one, two or three antihypertensive classes and had controlled BP (controlled hypertension [HTN]), 29% of them took one or two antihypertensive classes and had uncontrolled BP (uncontrolled HTN), and 32% of the patients took three antihypertensive classes or more and had uncontrolled BP (resistant HTN). The initiation of an antihypertensive drug and the factors affecting BP pressure were compared between the resistant and controlled HTN groups. Patients who initiated the study with ACEI were less likely to be resistant compared with those who started with alpha blockers and non-thiazide diuretics. Older patients, and high BMI tended to result in resistant HTN. In the second part of study, BP responses for patients who initiated the study with ACEI, ARB, BB, CCB and thiazide diuretics were compared. After adjusting for risk factors, patients who initiated the study with ACEI and ARB were more respondent than those who took CCB and thiazide diuretics. In the last part of this study, the association between BP reductions and factors affecting BP were tested for each antihypertensive drug. Older patients responded better to alpha blockers. Younger patients responded better to ACEI and ARB. An increase in BMI led to a decreased reduction in patients on ACEI and diuretics (thiazide and non-thiazide). An increase in albumin levels and a decrease in eGFR led to decreases in BP reductions in patients on thiazide diuretics. An increase in eGFR decreased the BP response with ACEI. In conclusion, although a high percentage of hypertensive patients in Scotland persisted with their initial drug prescription, low adherence rates were found with these patients. Approximately half of these patients required three different antihypertensive classes during the 5 years, and 32% of them had resistant HTN. Although this study was observational in nature, the large sample size in this study represented a real HTN population, and the large pharmacy data represented a real antihypertensive population, which were collected through the support of prescription data from the GBPC database. My findings suggest that ACEI, ARB and BB are less likely to require additional therapy. However, ACEI and ARB were better tolerated than BB in that they were more likely to be persistent than BB. In addition, users of ACEI, and ARB have good BP response and low resistant HTN. Linkage patients who participated in these studies with their morbidity and mortality will provide valuable information concerning the effect of adherence on morbidity and mortality and the potential benefits of using ACEI or ARB over other drugs.

Eficacia del aceite de oliva en la prevención de úlceras por presión en pacientes inmovilizados en atención primaria. Ensayo clínico aleatorizado, multicéntrico, paralelo, triple ciego, de no inferioridad

Las úlceras por presión representan un importante problema de salud pública y tienen un importante impacto económico en los sistemas de salud. La mayoría de los estudios para prevenir las úlceras por presión se han llevado a cabo en contextos hospitalarios, usando ácidos grasos hiperoxigenados (AGHO) y hasta la fecha, no se ha realizado ningún estudio específico con aceite de oliva virgen extra (AOVE) en el entorno domiciliario. Material y método Objetivo principal: evaluar si la utilización de AOVE no es inferior a los AGHO en la prevención de úlceras por presión (UPP) en pacientes inmovilizados en el entorno domiciliario. Diseño: Ensayo clínico aleatorizado multicéntrico, paralelo, a triple ciego, de no inferioridad. Ámbito: Población consultante de centros de salud andaluces. Muestra: 831 pacientes inmovilizados en riesgo de padecer UPP. Resultados El período de seguimiento fue de 16 semanas. En el análisis por protocolo, ninguna de las zonas evaluadas presentó diferencias de riesgo de incidencia de las úlceras por presión que superasen el valor delta establecido (10%). Sacro: AOVE 8 (2,55%) vs AGHO 8 (3,08%), RAR 0,53 (-2,2 a 3,26). Talón derecho: AOVE 4 (1,27%) vs AGHO 5 (1,92)%, RAR 0,65 (-1,43 a 2,73). Talón izquierdo: AOVE 3 (0,96%) vs AGHO 3 (1,15%), RAR 0.2 (-1,49 a 1,88). Trocánter Derecho: AOVE 0 (0%) vs AGHO 4 (1,54%), RAR 1,54 (0,04-3,03). Trocánter izquierdo: AOVE 1 (0,32%) vs AGHO 1 (0,38%), RAR 0.07 (-0,91 a 1,04). Discusión Este ensayo clínico pretendía evaluar si la prevención de las UPP usando una fórmula de AOVE no era inferior a la prevención de UPP con el uso AGHO, en el entorno domiciliario y con pacientes inmovilizados de alto riesgo. Los resultados han mostrado esta no inferioridad al no observarse diferencias que hayan superado el límite inferior del intervalo de confianza y convierte al aceite de oliva en un producto eficaz para la prevención de UPP en este tipo de pacientes. Se necesitan más estudios para investigar el mecanismo de acción del AOVE en la prevención de las UPP y relacionarlo con la etiopatogenia de éstas. Bibliografía 1. Gorecki C, Brown JM, Nelson EA, Briggs M, Schoonhoven L, Dealey C, et al. Impact of pressure ulcers on quality of life in older patients: a systematic review. J Am Geriatr Soc. 2009 Jul;57(7):1175–83. 2. Yamamoto Y, Hayashino Y, Higashi T, Matsui M, Yamazaki S, Takegami M, et al. Keeping vulnerable elderly patients free from pressure ulcer is associated with high caregiver burden in informal caregivers. J Eval Clin Pract. 2010 Jun;16(3):585–9. 3. Hanson D, Langemo DK, Anderson J, Thompson P, Hunter S. Friction and shear considerations in pressure ulcer development. Adv Skin Wound Care. 2010 Jan;23(1):21–4. 4. Soldevilla Agreda JJ, Torra i Bou J-E, Verdú Soriano J, López Casanova P. 3.er Estudio Nacional de Prevalencia de Úlceras por Presión en España, 2009: Epidemiología y variables definitorias de las lesiones y pacientes. Gerokomos. 2011 Jun;22(2):77–90. 5. Kottner J, Lahmann N, Dassen T. [Pressure ulcer prevalence: comparison between nursing homes and hospitals]. Pflege Z. 2010 Apr;63(4):228–31. 6. Wilborn D, Halfens R, Dassen T, Tannen A. [Pressure ulcer prevalence in German nursing homes and hospitals: what role does the National Nursing Expert Standard Prevention of Pressure Ulcer play?]. Gesundheitswesen Bundesverb Ärzte Öffentl Gesundheitsdienstes Ger. 2010 Apr;72(4):240–5. 7. Tubaishat A, Anthony D, Saleh M. Pressure ulcers in Jordan: a point prevalence study. J Tissue Viability. 2011 Feb;20(1):14–9. 8. James J, Evans JA, Young T, Clark M. Pressure ulcer prevalence across Welsh orthopaedic units and community hospitals: surveys based on the European Pressure Ulcer Advisory Panel minimum data set. Int Wound J. 2010 Jun;7(3):147–52. 9. Defloor T, Schoonhoven L, Katrien V, Weststrate J, Myny D. Reliability of the European Pressure Ulcer Advisory Panel classification system. J Adv Nurs. 2006 Apr;54(2):189–98

Are we teaching our students what they need to know about ageing? Results from the National Survey of Undergraduate Teaching in Ageing and Geriatric Medicine

Introduction - Learning about ageing and the appropriate management of older patients is important for all doctors. This survey set out to evaluate what medical undergraduates in the UK are taught about ageing and geriatric medicine and how this teaching is delivered. Methods – An electronic questionnaire was developed and sent to the 28/31 UK medical schools which agreed to participate. Results – Full responses were received from 17 schools. 8/21 learning objectives were recorded as taught, and none were examined, across every school surveyed. Elder abuse and terminology and classification of health were taught in only 8/17 and 2/17 schools respectively. Pressure ulcers were taught about in 14/17 schools but taught formally in only 7 of these and examined in only 9. With regard to bio- and socio- gerontology, only 9/17 schools reported teaching in social ageing, 7/17 in cellular ageing and 9/17 in the physiology of ageing. Discussion – Even allowing for the suboptimal response rate, this study presents significant cause for concern with UK undergraduate education related to ageing. The failure to teach comprehensively on elder abuse and pressure sores, in particular, may be significantly to the detriment of older patients.

Brachycephalic obstructive airway syndrome : a review with six clinical cases

Dissertação de Mestrado Integrado em Medicina Veterinária

L'activité tonique diaphragmatique chez les enfants avec et sans support respiratoire

Introduction : Les nourrissons, vu la grande compliance de leur cage thoracique, doivent maintenir activement leur volume pulmonaire de fin d’expiration (VPFE). Ceci se fait par interruption précoce de l’expiration, et par le freinage expiratoire au niveau laryngé et par la persistance de la contraction des muscles inspiratoires. Chez les nourrissons ventilés mécaniquement, notre équipe a montré que le diaphragme est activé jusqu’à la fin de l’expiration (activité tonique). Il n’est pas clair si cette activité tonique diaphragmatique compense pour l’absence de freinage laryngé liée à l’intubation endotrachéale. Objectif : Notre objectif est de déterminer si l’activité tonique diaphragmatique persiste après l’extubation chez les nourrissons et si elle peut être observée chez les enfants plus âgés. Méthode : Ceci est une étude observationnelle longitudinale prospective de patients âgés de 1 semaine à 18 ans admis aux soins intensifs pédiatriques (SIP), ventilés mécaniquement pour >24 heures et avec consentement parental. L’activité électrique du diaphragme (AEdi) a été enregistrée à l’aide d’une sonde nasogastrique spécifique à 4 moments durant le séjour aux SIP : en phase aigüe, pré et post-extubation et au congé. L’AEdi a été analysée de façon semi-automatique. L’AEdi tonique a été définie comme l’AEdi durant le dernier quartile de l’expiration. Résultats : 55 patients avec un âge médian de 10 mois (écart interquartile: 1-48) ont été étudiés. Chez les nourrissons (<1an, n=28), l’AEdi tonique en pourcentage de l’activité inspiratoire était de 48% (30-56) en phase aigüe, 38% (25-44) pré-extubation, 28% (17-42) post-extubation et 33% (22-43) au congé des SIP (p<0.05, ANOVA, avec différence significative entre enregistrements 1 et 3-4). Aucun changement significatif n’a été observé pré et post-extubation. L’AEdi tonique chez les patients plus âgés (>1an, n=27) était négligeable en phases de respiration normale (0.6mcv). Par contre, une AEdi tonique significative (>1mcv et >10%) a été observée à au moins un moment durant le séjour de 10 (37%) patients. La bronchiolite est le seul facteur indépendant associé à l’activité tonique diaphragmatique. Conclusion : Chez les nourrissons, l’AEdi tonique persiste après l’extubation et elle peut être réactivée dans certaines situations pathologiques chez les enfants plus âgés. Elle semble être un indicateur de l’effort du patient pour maintenir son VPFE. D’autres études devraient être menées afin de déterminer si la surveillance de l’AEdi tonique pourrait faciliter la détection de situations de ventilation inappropriée.

L'activité tonique diaphragmatique chez les enfants avec et sans support respiratoire

Introduction : Les nourrissons, vu la grande compliance de leur cage thoracique, doivent maintenir activement leur volume pulmonaire de fin d’expiration (VPFE). Ceci se fait par interruption précoce de l’expiration, et par le freinage expiratoire au niveau laryngé et par la persistance de la contraction des muscles inspiratoires. Chez les nourrissons ventilés mécaniquement, notre équipe a montré que le diaphragme est activé jusqu’à la fin de l’expiration (activité tonique). Il n’est pas clair si cette activité tonique diaphragmatique compense pour l’absence de freinage laryngé liée à l’intubation endotrachéale. Objectif : Notre objectif est de déterminer si l’activité tonique diaphragmatique persiste après l’extubation chez les nourrissons et si elle peut être observée chez les enfants plus âgés. Méthode : Ceci est une étude observationnelle longitudinale prospective de patients âgés de 1 semaine à 18 ans admis aux soins intensifs pédiatriques (SIP), ventilés mécaniquement pour >24 heures et avec consentement parental. L’activité électrique du diaphragme (AEdi) a été enregistrée à l’aide d’une sonde nasogastrique spécifique à 4 moments durant le séjour aux SIP : en phase aigüe, pré et post-extubation et au congé. L’AEdi a été analysée de façon semi-automatique. L’AEdi tonique a été définie comme l’AEdi durant le dernier quartile de l’expiration. Résultats : 55 patients avec un âge médian de 10 mois (écart interquartile: 1-48) ont été étudiés. Chez les nourrissons (<1an, n=28), l’AEdi tonique en pourcentage de l’activité inspiratoire était de 48% (30-56) en phase aigüe, 38% (25-44) pré-extubation, 28% (17-42) post-extubation et 33% (22-43) au congé des SIP (p<0.05, ANOVA, avec différence significative entre enregistrements 1 et 3-4). Aucun changement significatif n’a été observé pré et post-extubation. L’AEdi tonique chez les patients plus âgés (>1an, n=27) était négligeable en phases de respiration normale (0.6mcv). Par contre, une AEdi tonique significative (>1mcv et >10%) a été observée à au moins un moment durant le séjour de 10 (37%) patients. La bronchiolite est le seul facteur indépendant associé à l’activité tonique diaphragmatique. Conclusion : Chez les nourrissons, l’AEdi tonique persiste après l’extubation et elle peut être réactivée dans certaines situations pathologiques chez les enfants plus âgés. Elle semble être un indicateur de l’effort du patient pour maintenir son VPFE. D’autres études devraient être menées afin de déterminer si la surveillance de l’AEdi tonique pourrait faciliter la détection de situations de ventilation inappropriée.

Äldre invandrares från före detta Jugoslaviens förväntningar i mötet med sjuksköterskor i Sverige : -En kvalitativ intervjustudie

Dagens samhälle blir allt mer mångkulturellt. Det ställer högre krav på både omvårdnaden och sjuksköterskan. Sjuksköterskans eventuella brist på kompetens om kulturskillnader kan skapa kulturkrockar, missförstånd och felaktig omvårdnad. Syftet med studien var att undersöka vilka förväntningar äldre invandrare från förre detta Jugoslavien har i möten med sjuksköterskan i Sverige samt hur sjuksköterskans kompetens kan skiljas från undersköterskor, sjukgymnaster och arbetsterapeuter. Metod: Studien är kvalitativ med en induktiv ansats och baseras på sex intervjuer med äldre invandrare som ursprungligen kom från fd. Jugoslavien. Personlig kontakt togs med informanterna om deltagande i undersökningen genom serbiska/bosniska/kroatiska/makedoniska. Författaren informerade om studien och att de som ville delta kontaktade författaren. Insamlat material analyserades systematiskt med innehållsanalys. Resultat: Det som framkom att de äldre invandrarna förväntade sig i mötet med sjuksköterskan presenteras i följande fem kategorier; Att få bekräftelse för uttalade behov; Empatisk kontakt; Kommunikation och dialog i mötet; Respekt för sina värderingar och syn på hälsa och Trygghet. Slutsatsen: omvårdnad av äldre patienter med en annan kulturell bakgrund kräver båda kulturell kompetens och professionellt förhållningssätt. Sjuksköterskan behöver kunna identifiera patientens vårdbehov och i detta fallet även övergå de språkliga barriärer och nå patienten och förstå deras behov.