A prosztatarák gazdasági terhe nagy betegregiszterek alapján (The economic burden of prostate cancer. A systematic literature overview of registry-based studies)

INTRODUCTION: Prostate cancer, the most frequent malignant disease in males in Europe, accounts for a great proportion of health expenditures. AIM: A systematic review of registry-based studies about the cost-of-illness and related factors of prostate cancer, published in the last 10 years. METHOD: A MEDLINE-based literature review was carried out between January 1, 2003 and October 1, 2013. RESULTS: Fifteen peer-reviewed articles met the criteria of interest. In developed countries radiotherapy, surgical treatment and hormone therapy account for the greatest per capita costs. In Europe early stage tumours (4-7000 €, 2006), while in the USA metastatic prostate cancer (19 900-25 500 $, 2004) was associated with highest per capita expenses. In Europe the greatest costs incurred within the initial treatment (6400 €/6 months, 2008), while in the USA within the end-of-life care (depending on age: 62 200-93 400 $, 2010). CONCLUSIONS: Despite public health importance of prostate cancer, the cost-of-illness literature from Europe is relatively small.

Alcohol use and sexual victimization among Hispanic college women

Sexual victimization of young women typically occurs within a context of alcohol use, such that women are more likely to be victimized on days on which they consume alcohol compared to days on which no alcohol is consumed. Additionally, most research on sexual victimization of women has focused on forced sexual acts; consequently, little is known about forms sexual victimization that college women typically experience, such as brief (e.g., unwanted touching) or verbally coerced experiences (e.g., doing sexual things to prevent a partner from leaving). Finally, there is a need for more research on the processes underlying college women's drinking and the specific mechanisms through which drinking increases risk for sexual victimization. This dissertation sought to replicate recent findings of a temporal association between alcohol use and sexual victimization, and to investigate whether or not binge use increased risk for victimization, within a sample of young Hispanic college women, using repeated-measures logistic regression. This study also aimed to identify and explore typologies of victimization experiences in order to better understand types of sexual victimization common among young college women. Finally, the validity of a model of alcohol use and sexual victimization was investigated using structural equation modeling techniques. The results confirmed and extended previous research by demonstrating an increase in the conditional probability of sexual victimization on days of alcohol consumption compared with days of no alcohol consumption, and on days of binge alcohol consumption compared with days of moderate alcohol consumption. Sexual victimization experiences reported in this study were diverse, and cluster analysis was used to identify and explore specific typologies of victimization experiences, including intimate relationship victimization, brief victimization with stranger, prolonged victimization with acquaintance, and workplace victimization. The results from structural equation modeling (SEM) analyses were complex and helped to illuminate the relationships between reasons for drinking, alcohol use, childhood sexual abuse, sexual victimization, psychopathology, and acculturation-related factors among Hispanic college women. These findings have implications for the design of university-based prevention and intervention efforts aimed at reducing rates of alcohol-related sexual victimization within Hispanic populations.

What makes online grocers work? A case study analysis of factors contributing to online grocery store profitability

This research examined the factors contributing to the performance of online grocers prior to, and following, the 2000 dot.com collapse. The primary goals were to assess the relationship between a company’s business model(s) and its performance in the online grocery channel and to determine if there were other company and/or market related factors that could account for company performance. ^ To assess the primary goals, a case based theory building process was utilized. A three-way cross-case analysis comprising Peapod, GroceryWorks, and Tesco examined the common profit components, the structural category (e.g., pure-play, partnership, and hybrid) profit components, and the idiosyncratic profit components related to each specific company. ^ Based on the analysis, it was determined that online grocery store business models could be represented at three distinct, but hierarchically, related levels. The first level was termed the core model and represented the basic profit structure that all online grocers needed in order to conduct operations. The next model level was termed the structural model and represented the profit structure associated with the specific business model configuration (i.e., pure-play, partnership, hybrid). The last model level was termed the augmented model and represented the company’s business model when idiosyncratic profit components were included. In relation to the five company related factors, scalability, rate of expansion, and the automation level were potential candidates for helping to explain online grocer performance. In addition, all the market structure related factors were deemed possible candidates for helping to explain online grocer performance. ^ The study concluded by positing an alternative hypothesis concerning the performance of online grocers. Prior to this study, the prevailing wisdom was that the business models were the primary cause of online grocer performance. However, based on the core model analysis, it was hypothesized that the customer relationship activities (i.e., advertising, promotions, and loyalty program tie-ins) were the real drivers of online grocer performance. ^

Relationships among dietary intake, dietary patterns, dietary quality and nutrient adequacy and substance use in Latina mother/daughter dyads

This study examined the relationships among dietary intake, substance use, socioeconomic and acculturation-related factors among Latinas in Miami-Dade County. Substance abuse is rising among Latinas. A fuller understanding of this problem is needed given the rise of the Hispanic population and the role of women in Latin society. A better understanding between substance use and dietary intake can guide nutrition interventions to reduce negative substance-related health consequences. A purposeful sample of 320 Latina mother/daughter dyads were recruited and interviewed face-to-face as part of the Latino Women's Study. Dietary intake was collected via a 24-hour recall and examined by (1) nutrient intake, (2) dietary patterns using cluster analysis, (3) quality of diet using the Healthy Eating Index (HEI) and (4) the Dietary Reference Intakes to determine nutrient adequacy. Substance use was measured with the Drug Use Frequency and the Healthy and Daily Living Form. Acculturation was measured with the Cultural Identity Scale. Three dietary patterns emerged based on the number of servings from the food groups established in MyPyramid. None were associated with substance use. Latinas who reported using cannabis, cocaine, sedatives without prescription and/or more than five alcoholic drinks on an occasion at least once a month during the previous twelve months had significantly lower HEI scores (64 vs. 60; F = 7.8, p = .005) and consumed fewer fruits (F = 16, p < .001) than non-users. Latinas classified as mothers whom reported consuming cannabis at least 1-7 times a week had significantly lower HEI scores (F = 4.23, p = .015, η2 = .027) than daughters with the same frequency of substance use. One dimension of acculturation, greater familiarity with Latin culture, was associated with good dietary quality (β = .142, p = .012) regardless of any type of substance used or income level. There was a high prevalence of inadequacy of folic acid intake (50-75%) regardless of substance use. Substance users consumed significantly more energy (1,798 vs. 1,615; p = .027) than non-users. Although effect sizes were small, associations between dietary intake and substance use among Latinas deserve further exploration while acknowledging the combined association with acculturation. ^

Glycemic control: Risk factors, quality of life, workforce participation, and mortality among US adults with type 2 diabetes

Despite research showing the benefits of glycemic control, it remains suboptimal among adults with diabetes in the United States. Possible reasons include unaddressed risk factors as well as lack of awareness of its immediate and long term consequences. The objectives of this study were to, using cross-sectional data, (1) ascertain the association between suboptimal (Hemoglobin A1c (HbA1c) .7%), borderline (HbA1c 7-8.9%), and poor (HbA1c .9%) glycemic control and potentially new risk factors (e.g. work characteristics), and (2) assess whether aspects of poor health and well-being such as poor health related quality of life (HRQOL), unemployment, and missed-work are associated with glycemic control; and (3) using prospective data, assess the relationship between mortality risk and glycemic control in US adults with type 2 diabetes. Data from the 1988-1994 and 1999-2004 National Health and Nutrition Examination Surveys were used. HbA1c values were used to create dichotomous glycemic control indicators. Binary logistic regression models were used to assess relationships between risk factors, employment status and glycemic control. Multinomial logistic regression analyses were conducted to assess relationships between glycemic control and HRQOL variables. Zero-inflated Poisson regression models were used to assess relationships between missed work days and glycemic control. Cox-proportional hazard models were used to assess effects of glycemic control on mortality risk. Using STATA software, analyses were weighted to account for complex survey design and non-response. Multivariable models adjusted for socio-demographics, body mass index, among other variables. Results revealed that being a farm worker and working over 40 hours/week were risk factors for suboptimal glycemic control. Having greater days of poor mental was associated with suboptimal, borderline, and poor glycemic control. Having greater days of inactivity was associated with poor glycemic control while having greater days of poor physical health was associated with borderline glycemic control. There were no statistically significant relationships between glycemic control, self-reported general health, employment, and missed work. Finally, having an HbA1c value less than 6.5% was protective against mortality. The findings suggest that work-related factors are important in a person’s ability to reach optimal diabetes management levels. Poor glycemic control appears to have significant detrimental effects on HRQOL.^

Glycemic Control: Risk Factors, Quality of Life, Workforce Participation, and Mortality Among US Adults with Type 2 Diabetes

Despite research showing the benefits of glycemic control, it remains suboptimal among adults with diabetes in the United States. Possible reasons include unaddressed risk factors as well as lack of awareness of its immediate and long term consequences. The objectives of this study were to, using cross-sectional data, 1) ascertain the association between suboptimal (Hemoglobin A1c (HbA1c) ≥7%), borderline (HbA1c 7-8.9%), and poor (HbA1c ≥9%) glycemic control and potentially new risk factors (e.g. work characteristics), and 2) assess whether aspects of poor health and well-being such as poor health related quality of life (HRQOL), unemployment, and missed-work are associated with glycemic control; and 3) using prospective data, assess the relationship between mortality risk and glycemic control in US adults with type 2 diabetes. Data from the 1988-1994 and 1999-2004 National Health and Nutrition Examination Surveys were used. HbA1c values were used to create dichotomous glycemic control indicators. Binary logistic regression models were used to assess relationships between risk factors, employment status and glycemic control. Multinomial logistic regression analyses were conducted to assess relationships between glycemic control and HRQOL variables. Zero-inflated Poisson regression models were used to assess relationships between missed work days and glycemic control. Cox-proportional hazard models were used to assess effects of glycemic control on mortality risk. Using STATA software, analyses were weighted to account for complex survey design and non-response. Multivariable models adjusted for socio-demographics, body mass index, among other variables. Results revealed that being a farm worker and working over 40 hours/week were risk factors for suboptimal glycemic control. Having greater days of poor mental was associated with suboptimal, borderline, and poor glycemic control. Having greater days of inactivity was associated with poor glycemic control while having greater days of poor physical health was associated with borderline glycemic control. There were no statistically significant relationships between glycemic control, self-reported general health, employment, and missed work. Finally, having an HbA1c value less than 6.5% was protective against mortality. The findings suggest that work-related factors are important in a person’s ability to reach optimal diabetes management levels. Poor glycemic control appears to have significant detrimental effects on HRQOL.

Diagnósticos de enfermagem do domínio nutrição em pacientes submetidos à hemodiálise

The study aimed to analyze the nursing diagnoses of the nutrition domain from NANDA International in patients undergoing hemodialysis. This is a transversal study conducted in a university hospital in northeastern Brazil, with 50 hemodialysis patients. The data collection instrument was an interview form and a physical examination, in digital format, applied between the months of December 2013 to May 2014. Data analysis was divided into two stages. In the first, defining characteristics, related factors and risk factors were judged as to their presence by the researcher, according to the data collected. In the second stage, based on data from the first, diagnostic inference by experts was held. The results were organized in tables and analyzed using descriptive and inferential statistics for the diagnoses that showed higher frequencies than 50%. The project was approved by the Ethics Committee responsible for the research institution (protocol number 392 535), with Certificate Presentation to Ethics Assessment 18710613.4.00005537 number. The results indicate a median of 7 (± 1.51) nursing diagnoses of the nutrition domain per patient. Six diagnoses with greater frequency than 50% were identified, namely: Risk for electrolyte imbalance, Risk for unstable blood glucose level, Excess fluid volume, Readiness for enhanced fluid balance, Readiness for enhanced nutrition and Risk for deficient fluid volume. The defining characteristics, related and risk factors presented an average of 34.78 (± 6.86), 15.50 (± 3.40) and a median of 4 (± 1.93), respectively, and 11 of these components had statistically significant association with the respective diagnoses. Were identified associations between adventitious breath sounds, edema and pulmonary congestion with the diagnosis Excess fluid volume; Expressed desire to increase fluid balance with the nursing diagnosis Readiness for enhanced fluid balance; It feeds regularly, Attitude to food consistent with the health goals, Consume adequate food, expresses knowledge about healthy food choices, expresses desire to improve nutrition, expresses knowledge about liquid healthier choices and following appropriate standard supply with diagnosis Readiness for enhanced nutrition. It is concluded that the diagnosis of the nutrition domain related to electrolyte problems are prevalent in customer submitted to hemodialysis. The identification of these diagnoses contributes to the development of a plan of care targeted to the needs of these clients, providing better quality of life and advance in the practice of care

Análise de conceito do diagnóstico de enfermagem autocontrole ineficaz da saúde em pacientes submetidos à hemodiálise

The concept analysis process carefully examines the description and uses of a word or term, enabling the standardization of language, in addition to providing representation to the profession, and facilitate the work of taxonomies. The aim of the study was to analyze the concept of nursing diagnosis ineffective self-health in patients undergoing hemodialysis. Study concept analysis, based on Walker and Avant model and operationalized through integrative literature review. The databases searched were: SCOPUS, CINAHL, PUBMED, LILACS and COCHRANE, with descriptors: Selfmanagement, Adherence and Hemodialysis. The inclusion criteria were: articles published in the last five years, complete articles are available free in selected databases; articles available in Portuguese, English or Spanish; and articles that address the self-concept of health, the antecedents and the consequent. And Exclusion: editorials, letters to the editor, theses and dissertations. The survey of the articles occurred in the months from January to March 2014. The initial sample of 16785 articles, with 11748 in PUBMED, 4767 in Scopus, 174 in CINAHL, the Cochrane 70 and 26 in LILACS. After applying the criteria, 76 articles were selected, 19 in CINAHL, 18 in PUBMED, 30 in Scopus, and 9 in LILACS. In analyzing the data, given that the concept was sought in the literature was self-health, was held interpretation to ineffective self-health diagnosis through the transposition in the denial of the attributes, antecedents and consequences identified. It is noteworthy that the terms identified in the literature as defining characteristics and related factors of the diagnosis under study were added to the survey, not even the transposition into opposite term is possible. The results show that the concept developed for the inefficient self-health diagnosis was: the patient's inability to control habits and achieve the negotiated with professionals therapeutic targets, resulting in health complications. 33 antecedents relating to social, psychological and therapeutic aspects and 16 consequential, involving physiological, social, psychological and therapeutic aspects were identified. Thus, it is concluded that the ineffective self-health concept is broad and involves individual patient factors and the therapeutic relationship between patient and professionals. It is believed that the study contributed to the improvement of diagnosis in renal clientele, besides being an important base for the growth of the scientific body of nursing, subsidizing the development of own technology area

Validação do conteúdo do diagnóstico de enfermagem proteção ineficaz para pacientes submetidos à hemodiálise

Methodological study, in order to validate the content of the nursing diagnosis protection ineffective in patients undergoing hemodialysis. The research took place in two stages, namely: concept analysis and content analysis of the instrument by experts. T he first step was operationalized through an integrative review of the databaes LILACS, CINAHL, PubMed, Scopus and Cochrane, with the key words protection and hemodialysis, in October and November 2013. The sample consisted of 32 articles, which were analyz ed by a c areful reading to identify the sections that correspond ed to the defining attributes , antecedents and consequences of protection in patients undergoing hemodialysis. T he interpretation for the diagnosis of effective protection was made by transpos ing the components of the diagnosis (definition, defining characteristics and related factors) to the denial form . In the second stage, we elaborated an instrument with the components of the nursing diagnostic s studied and proceeded to the analysis conduct ed in April 2014 by 22 specialists in nephrology and in the terminology of the NANDA International, selected by means of th e Lattes Platform . We used the binomial test to assess the proportion of experts who rated each item as appropriate, considering a si gnificance level of 5%. The project was approved by the Ethics Committee of the institution responsible for the research, an opinion on num b er 387 837 and CAAE 18486413.0.0000.5537. The results show that the proposal for the nursing diagnosis of ineffectiv e protection in patients undergoing hemodialysis is: definition - the same as that presented in the NANDA International Taxonomy II, location - domain safety / protection and class injury. Related factors are: Absence of routine vaccines; Non - adherence to care related to vascular access; Non - adherence to infection control measures; Non - adherence to prescribed diet; Non - adherence to drug therapy; Presence of comorbidities; Drug abuse; Immune disorders; Extremes of age; Abnormal blood profiles; Drugs that red uce immunity; and side effects and adverse treatment - related. The defining characteristics are: Presence of invading the bloodstream; Nutritional disorders; Increase in the number of hospitalizations; Uncontrolled dry weight; Infected vascular access; Vasc ular inadequate access; Increased blood pressure; fever; Bleeding disorder; Disability immunity; fatigue; weakness; itching; and maladaptive response to stress. It follows that the identification of the defining attributes, antecedents and consequences inc reased the wealth of vocabulary, allowing the construction of theoretical and empirical definitions for a broader understanding of the concept protection. Furthermore, the study contributed to the enrichment of nursing specific body of knowledge, as well a s in the direction of nursing care for patients undergoing hemodialysis.

Estudo do domínio segurança/proteção da NANDA internacional em pacientes de unidade de terapia intensiva

The study aimed to analyze the field of nursing diagnoses safety / protection of NANDA International present in patients in the Intensive Care Unit. This is a crosssectional study in intensive care complex of a university hospital in northeastern Brazil. The research took place in two stages. The first step was to collect data through an interview form and physical examination, with 86 patients admitted to the unit, during the months of December 2013 to May 2014. Spreadsheets were built in Microsoft Office Excel 2010 Software in which were marked by the researcher of this study, the presence or absence of defining characteristics, related factors and risk factors of the 31 studied diagnoses. In the second stage, held between July and August 2014, the sheets were sent to three diagnosticians, previously trained to perform the diagnostic inference. Data were analyzed using descriptive and inferential statistics for the diagnoses that showed higher frequencies than 50%, using IBM SPSS version 20.0 for Statistic Windows.O project was approved by the 440/414 and Presentation Certificate for Ethics Assessment number 22955113 .2.0000.5292. The results indicated the presence of 29 field of nursing diagnoses safety / protection in hospital clientele in the Intensive Care Unit, of which five were present in 100% of patients, namely: Risk of contamination, injury risk, falls risk,risk of allergic response and risk of trauma. Diagnoses that presented more frequently than 50% were: Risk of infection, dry eye risk, poisoning risk, vascular trauma risk, impaired skin integrity, impaired dentition, bleeding risk, risk imbalance in body temperature, Risk perioperative positioning injury, impaired tissue integrity, peripheral neurovascular dysfunction Risk, Risk adverse response to contrast media with iodine, shock Hazard and Risk of aspiration. For these analyzes, we identified 35 risk factors, 11 defining characteristics and three related factors showed statistically significant association with the studied diagnoses. For diagnostics: Risk of contamination, injury risk, falls risk, allergic response risk, trauma Risk, Risk of infection, dry eye risk and risk poisoning there was no association with any of their risk factors. We conclude that most of the area of nursing diagnoses safety / protection feature is prevalent in critically ill patients, with special attention to the risk diagnoses. There was a significant association between these diagnoses and its components. It is noteworthy, therefore, that the lifting of this profile contributes relevant clues to the inference of the priority nursing diagnoses domain safety / protection in the study population, supporting the practice of nursing and stimulating knowledge on the subject.

Oxygen content and paleoproductivity from surface sediment samples Y69-86 to PLDS-004G

Quantitative estimation of surface ocean productivity and bottom water oxygen concentration with benthic foraminifera was attempted using 70 samples from equatorial and North Pacific surface sediments. These samples come from a well defined depth range in the ocean, between 2200 and 3200 m, so that depth related factors do not interfere with the estimation. Samples were selected so that foraminifera were well preserved in the sediments and temperature and salinity were nearly uniform (T = 1.5° C; S = 34.6 per mil). The sample set was also assembled so as to minimize the correlation often seen between surface ocean productivity and bottom water oxygen values (r**2 = 0.23 for prediction purposes in this case). This procedure reduced the chances of spurious results due to correlations between the environmental variables. The samples encompass a range of productivities from about 25 to >300 gC m**-2 yr**-1, and a bottom water oxygen range from 1.8 to 3.5 ml/L. Benthic foraminiferal assemblages were quantified using the >62 µm fraction of the sediments and 46 taxon categories. MANOVA multivariate regression was used to project the faunal matrix onto the two environmental dimensions using published values for productivity and bottom water oxygen to calibrate this operation. The success of this regression was measured with the multivariate r? which was 0.98 for the productivity dimension and 0.96 for the oxygen dimension. These high coefficients indicate that both environmental variables are strongly imbedded in the faunal data matrix. Analysis of the beta regression coefficients shows that the environmental signals are carried by groups of taxa which are consistent with previous work characterizing benthic foraminiferal responses to productivity and bottom water oxygen. The results of this study suggest that benthic foraminiferal assemblages can be used for quantitative reconstruction of surface ocean productivity and bottom water oxygen concentrations if suitable surface sediment calibration data sets are developed and appropriate means for detecting no-analog samples are found.

Planktic foraminiferal and sea surface temperature record during the last 1 Myr across the Subtropical Front, Southwest Pacific

Planktic foraminiferal faunas and modern analogue technique estimates of sea surface temperature (SST) for the last 1 million years (Myr) are compared between core sites to the north (ODP 1125, 178 faunas) and south (DSDP 594, 374 faunas) of the present location of the Subtropical Front (STF), east of New Zealand. Faunas beneath cool subtropical water (STW) north of the STF are dominated by dextral Neogloboquadrina pachyderma, Globorotalia inflata, and Globigerina bulloides, whereas faunas to the south are strongly dominated by sinistral N. pachyderma (80-95% in glacials), with increased G. bulloides (20-50%) and dextral N. pachyderma (15-50%) in interglacials (beneath Subantarctic Water, or SAW). Canonical correspondence analysis indicates that at both sites, SST and related factors were the most important environmental influences on faunal composition. Greater climate-related faunal fluctuations occur in the south. Significant faunal changes occur through time at both sites, particularly towards the end of the mid-Pleistocene climate transition, MIS18-15 (e.g., decline of Globorotalia crassula in STW, disappearance of Globorotalia puncticulata in SAW), and during MIS8-5. Interglacial SST estimates in the north are similar to the present day throughout the last 1 Myr. To the south, interglacial SSTs are more variable with peaks 4-7 °C cooler than present through much of the early and middle Pleistocene, but in MIS11, MIS5.5, and early MIS1, peaks are estimated to have been 2-4 °C warmer than present. These high temperatures are attributed to southward spread of the STF across the submarine Chatham Rise, along which the STF appears to have been dynamically positioned throughout most of the last 1 Myr. For much of the last 1 Myr, glacial SST estimates in the north were only 1-2 °C cooler than the present interglacial, except in MIS16, MIS8, MIS6, and MIS4-2 when estimates are 4-7 °C cooler. These cooler temperatures are attributed to jetting of SAW through the Mernoo Saddle (across the Chatham Rise) and/or waning of the STW current. To the south, glacial SST estimates were consistently 10-11 °C cooler than present, similar to temperatures and faunas currently found in the vicinity of the Polar Front. One interpretation is that these cold temperatures reflect thermocline changes and increased Circumpolar Surface Water spinning off the Subantarctic Front as an enhanced Bounty Gyre along the south side of the Chatham Rise. For most of the last 1 Myr, the temperature gradient across the STF has been considerably greater than the present 4 °C. During glacial episodes, the STF in this region did not migrate northwards, but instead there was an intensification of the temperature gradient across it (interglacials 4-11 °C; glacials 8-14 °C).

The determinants of R&D investment: A survey of the empirical research

This paper offers an extensive survey and a critical discussion of the empirical literature on the driving factors of R&D. These factors are subsumed under five broad types. The paper first summarises the key predictions from theory regarding each type's R&D effect. It then examines for which factors differences in the theoretical predictions can also be found in empirical studies, and for which factors the empirical evidence is more unanimous. As the focus is on the empirical literature, methodological issues are also highlighted. The major factor types identified in the literature are, individual firm or industry characteristics, particularly internal finance and sales; competition in product markets; R&D tax credits and subsidies; location and resource related factors, such as spillovers from university research within close geographic proximity, membership of a research joint venture and cooperation with research centres, and the human capital embodied in knowledge workers; and spillovers from foreign R&D. Although on balance there is a consensus regarding the R&D effects of most factors, there is also variation in results. Recent work suggests that accounting for non-linearities is one area of research that may explain and encompass contradictory findings.

Effet préventif de la milrinone inhalée chez les patients avec hypertension pulmonaire subissant une chirurgie cardiaque sous circulation extracorporelle : une approche pharmacométrique

La circulation extracorporelle (CEC) est une technique utilisée en chirurgie cardiaque effectuée des milliers de fois chaque jour à travers le monde. L’instabilité hémodynamique associée au sevrage de la CEC difficile constitue la principale cause de mortalité en chirurgie cardiaque et l’hypertension pulmonaire (HP) a été identifiée comme un des facteurs de risque les plus importants. Récemment, une hypothèse a été émise suggérant que l'administration prophylactique (avant la CEC) de la milrinone par inhalation puisse avoir un effet préventif et faciliter le sevrage de la CEC chez les patients atteints d’HP. Toutefois, cette indication et voie d'administration pour la milrinone n'ont pas encore été approuvées par les organismes réglementaires. Jusqu'à présent, la recherche clinique sur la milrinone inhalée s’est principalement concentrée sur l’efficacité hémodynamique et l'innocuité chez les patients cardiaques, bien qu’aucun biomarqueur n’ait encore été établi. La dose la plus appropriée pour l’administration par nébulisation n'a pas été déterminée, de même que la caractérisation des profils pharmacocinétiques (PK) et pharmacodynamiques (PD) suite à l'inhalation. L'objectif de notre recherche consistait à caractériser la relation exposition-réponse de la milrinone inhalée administrée chez les patients subissant une chirurgie cardiaque sous CEC. Une méthode analytique par chromatographie liquide à haute performance couplée à un détecteur ultraviolet (HPLC-UV) a été optimisée et validée pour le dosage de la milrinone plasmatique suite à l’inhalation et s’est avérée sensible et précise. La limite de quantification (LLOQ) était de 1.25 ng/ml avec des valeurs de précision intra- et inter-dosage moyennes (CV%) <8%. Des patients souffrant d’HP pour lesquels une chirurgie cardiaque sous CEC était prévue ont d’abord été recrutés pour une étude pilote (n=12) et, par la suite, pour une étude à plus grande échelle (n=28) où la milrinone (5 mg) était administrée par inhalation pré-CEC. Dans l'étude pilote, nous avons comparé l'exposition systémique de la milrinone peu après son administration avec un nébuliseur pneumatique ou un nébuliseur à tamis vibrant. L’efficacité des nébuliseurs en termes de dose émise et dose inhalée a également été déterminée in vitro. Dans l'étude à plus grande échelle conduite en utilisant exclusivement le nébuliseur à tamis vibrant, la dose inhalée in vivo a été estimée et le profil pharmacocinétique de la milrinone inhalée a été pleinement caractérisé aux niveaux plasmatique et urinaire. Le ratio de la pression artérielle moyenne sur la pression artérielle pulmonaire moyenne (PAm/PAPm) a été choisi comme biomarqueur PD. La relation exposition-réponse de la milrinone a été caractérisée pendant la période d'inhalation en étudiant la relation entre l'aire sous la courbe de l’effet (ASCE) et l’aire sous la courbe des concentrations plasmatiques (ASC) de chacun des patients. Enfin, le ratio PAm/PAPm a été exploré comme un prédicteur potentiel de sortie de CEC difficile dans un modèle de régression logistique. Les expériences in vitro ont démontré que les doses émises étaient similaires pour les nébuliseurs pneumatique (64%) et à tamis vibrant (68%). Cependant, la dose inhalée était 2-3 fois supérieure (46% vs 17%) avec le nébuliseur à tamis vibrant, et ce, en accord avec les concentrations plasmatiques. Chez les patients, en raison des variations au niveau des facteurs liés au circuit et au ventilateur causant une plus grande dose expirée, la dose inhalée a été estimée inférieure (30%) et cela a été confirmé après récupération de la dose de milrinone dans l'urine 24 h (26%). Les concentrations plasmatiques maximales (Cmax: 41-189 ng/ml) et l'ampleur de la réponse maximale ΔRmax-R0 (0-65%) ont été observées à la fin de l'inhalation (10-30 min). Les données obtenues suite aux analyses PK sont en accord avec les données publiées pour la milrinone intraveineuse. Après la période d'inhalation, les ASCE individuelles étaient directement reliées aux ASC (P=0.045). Enfin, notre biomarqueur PD ainsi que la durée de CEC ont été identifiés comme des prédicteurs significatifs de la sortie de CEC difficile. La comparaison des ASC et ASCE correspondantes a fourni des données préliminaires supportant une preuve de concept pour l'utilisation du ratio PAm/PAPm comme biomarqueur PD prometteur et justifie de futures études PK/PD. Nous avons pu démontrer que la variation du ratio PAm/PAPm en réponse à la milrinone inhalée contribue à la prévention de la sortie de CEC difficile.

What Makes Online Grocers Work? A Case Study Analysis of Factors Contributing to Online Grocery Store Profitability

This research examined the factors contributing to the performance of online grocers prior to, and following, the 2000 dot.com collapse. The primary goals were to assess the relationship between a company’s business model(s) and its performance in the online grocery channel and to determine if there were other company and/or market related factors that could account for company performance. To assess the primary goals, a case based theory building process was utilized. A three-way cross-case analysis comprising Peapod, GroceryWorks, and Tesco examined the common profit components, the structural category (e.g., pure-play, partnership, and hybrid) profit components, and the idiosyncratic profit components related to each specific company. Based on the analysis, it was determined that online grocery store business models could be represented at three distinct, but hierarchically, related levels. The first level was termed the core model and represented the basic profit structure that all online grocers needed in order to conduct operations. The next model level was termed the structural model and represented the profit structure associated with the specific business model configuration (i.e., pure-play, partnership, hybrid). The last model level was termed the augmented model and represented the company’s business model when idiosyncratic profit components were included. In relation to the five company related factors, scalability, rate of expansion, and the automation level were potential candidates for helping to explain online grocer performance. In addition, all the market structure related factors were deemed possible candidates for helping to explain online grocer performance. The study concluded by positing an alternative hypothesis concerning the performance of online grocers. Prior to this study, the prevailing wisdom was that the business models were the primary cause of online grocer performance. However, based on the core model analysis, it was hypothesized that the customer relationship activities (i.e., advertising, promotions, and loyalty program tie-ins) were the real drivers of online grocer performance.