Public health impact of statin prescribing strategies based on jupiter

Texte intégral: http://www.springerlink.com/content/3q68180337551r47/fulltext.pdf

Free-breathing renal magnetic resonance angiography with steady-state free-precession and slab-selective spin inversion combined with radial k-space sampling and water-selective excitation.

The impact of radial k-space sampling and water-selective excitation on a novel navigator-gated cardiac-triggered slab-selective inversion prepared 3D steady-state free-precession (SSFP) renal MR angiography (MRA) sequence was investigated. Renal MRA was performed on a 1.5-T MR system using three inversion prepared SSFP approaches: Cartesian (TR/TE: 5.7/2.8 ms, FA: 85 degrees), radial (TR/TE: 5.5/2.7 ms, FA: 85 degrees) SSFP, and radial SSFP combined with water-selective excitation (TR/TE: 9.9/4.9 ms, FA: 85 degrees). Radial data acquisition lead to significantly reduced motion artifacts (P < 0.05). SNR and CNR were best using Cartesian SSFP (P < 0.05). Vessel sharpness and vessel length were comparable in all sequences. The addition of a water-selective excitation could not improve image quality. In conclusion, radial k-space sampling reduces motion artifacts significantly in slab-selective inversion prepared renal MRA, while SNR and CNR are decreased. The addition of water-selective excitation could not improve the lower CNR in radial scanning.

Impact of tamoxifen dose on tamoxifen and its active metabolites exposure in breast cancer patients: preliminary results from a prospective, open-label trial

Background: CYP2D6 is the key enzyme responsible for tamoxifen bioactivation mainly into endoxifen. This gene is highly polymorphic and breast cancer patients classified as CYP2D6 poor metabolizers (PM) or intermediate metabolizers (IM) appear to show low concentrations of endoxifen and to achieve less benefit from tamoxifen treatment. Purpose: This prospective, open-label trial aimed to assess how the increase of tamoxifen dose influences the level of endoxifen in the different genotype groups (poor-, intermediate-, and extensive-metabolizers (EM)). We examined the impact of doubling tamoxifen dose to 20mg twice daily on endoxifen plasma concentrations across these genotype groups. Patients and methods: Patients were assayed for CYP2D6 genotype and phenotype using dextromethorphan test. Tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen plasma levels were determined on 2 occasions at baseline (20mg/day of tamoxifen) and at day 30, 90 and 120 after dose increase (20 mg twice daily) using liquid chromatography-tandem-mass spectrometry. Endoxifen plasma levels were measured 6 to 24 hours after last drug intake to evaluate its accumulation before and after doubling tamoxifen dosage. ANOVA was used to evaluate endoxifen levels increase and difference between genotype groups. Results: 63 patients are available for analysis to date. Tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen plasma reached steady state at 30 day after tamoxifen dose escalation, with a significant increase compared to baseline by 1.6 to 1.8 fold : geometric mean plasma concentrations (CV %) were 140 ng/mL (45%) at baseline vs 255 (47%) at day 30 for tamoxifen (P < 0.0001); 256 (49%) vs 408 (64%) for N-desmethyltamoxifen (P < 0.0001); 2.4 (46%) vs 3.9 (51%) for 4-OH-tamoxifen (P < 0.0001); and 20 (91%) vs 33 (91%) for endoxifen (P < 0.02). On baseline, endoxifen levels tended to be lower in PM: 7 ng/mL (36%), than IM: 16 ng/mL (70%), P=0.08, and EM: 24 ng/mL (71%), P<0.001. After doubling tamoxifen dosage, endoxifen concentrations rose similarly in PM, IM and EM with respectively, 1.5 (18%), 1.5 (28%) and 1.7 (30%) fold increase from baseline, P=0.18. Conclusion: Endoxifen exposure varies widely under standard tamoxifen dosage, with CYP2D6 genotype explaining only a minor part of this variability. It increases consistently on doubling tamoxifen dose, similarly across genotypes. This would enable exposure optimization based on concentration monitoring.

Changes in patterns of practice for prostate cancer radiotherapy in Italy 1995-2003. A survey of the Prostate Cancer Study Group of the Italian Radiation Oncology Society.

Aims and background. In 2002, a survey including 1759 patients treated from 1980 to 1998 established a "benchmark" Italian data source for prostate cancer radiotherapy. This report updates the previous one. Methods. Data on clinical management and outcomes of 3001 patients treated in 15 centers from 1999 through 2003 were analyzed and compared with those of the previous survey. Results. Significant differences in clinical management (-10% had abdominal ma-gnetic resonance imaging; +26% received ≥70 Gy, +48% conformal radiotherapy, -20% pelvic radiotherapy) and in G3-4 toxicity rates (-3.8%) were recorded. Actuarial 5-year overall, disease-specific, clinical relapse-free, and biochemical relapse-free survival rates were 88%, 96%, 96% and 88%, respectively. At multivariate analysis, D'Amico risk categories significantly impacted on all the outcomes; higher radiotherapy doses were significantly related with better overall survival rates, and a similar trend was evident for disease-specific and biochemical relapse-free survival; cumulative probability of 5-year late G1-4 toxicity was 24.8% and was significantly related to higher radiotherapy doses (P <0.001). Conclusions. The changing patterns of practice described seem related to an improvement in efficacy and safety of radiotherapy for prostate cancer. However, the impact of the new radiotherapy techniques should be prospectively evaluated.

Carotid Dose Spring in Definitive Irradiation of T1N0 Squamous Cell Laryngeal Carcinoma Using Helical Tomotherapy

Purpose/Objective(s): To implement a carotid dose sparing protocol using helical Tomotherapy in T1N0 squamous cell laryngeal carcinoma.Materials/Methods: Between July and August 2010, 7 men with stage T1N0 laryngeal carcinoma were included in this study. Age ranged from 47 - 74 years. Staging included endoscopic examination, CT-scan and MRI when indicated. Planned irradiation dose was 70 Gy in 35 fractions over 7 weeks. A simple treatment planning algorithm for carotid sparing was used: maximum point dose to the carotids 35 Gy, to the spinal cord 30 Gy, and 100% PTV volume to be covered with 95% of the prescribed dose. Carotid volume of interest extended to 1 cm above and below of the PTV. Doses to the carotid arteries, to the critical organs, and to the planned target volume (PTV) with our standard laryngeal irradiation protocol was compared. Daily megavoltage scans were obtained before each fraction. When necessary, the Planned Adaptive software (TomoTherapy Inc., Madison, WI) was used to evaluatethe need for a re-planning, which has never been indicated. Dose data were extracted using the VelocityAI software (Atlanta, GA), and data normalization and dose-volume histogram (DVH) interpolation were realized using the Igor Pro software (Portland, OR).Results:A significant (p\0.05) carotid dose sparing compared to our standard protocol with an average maximum point dose of 38.3 Gy (standard deviation [SD] 4.05 Gy), average mean dose of 18.59 Gy (SD 0.83 Gy) was achieved. In all patients, 95% of the carotid volume received less than 28.4 Gy (SD 0.98 Gy). The average maximum point dose to the spinal cord was 25.8 Gy (SD 3.24 Gy). PTV was fully covered with more than 95% of the prescribed dose for all patients with an average maximum point dose of 74.1 Gy and the absolute maximum dose in a single patient of 75.2 Gy. To date, the clinical outcomes have been excellent. Three patients (42%) developed stage 1 mucositis that was conservatively managed, and all the patients presented a mild to moderate dysphonia. All adverse effects resolved spontaneously in the month following the end of treatment. Early local control rate is 100% considering a 4 - 5 months post treatment follow-up.Conclusions: Helical Tomotherapy allows a clinically significant decrease of carotid irradiation dose compared to standard irradiation protocols with an acceptable spinal cord dose tradeoff. Moreover, this technique allows the PTV to be homogenously covered with a curative irradiation dose. Daily control imaging brings added security margins especially when working with high dose gradients. Further investigations and follow-up are underway to better evaluate the late clinical outcomes especially the local control rate, late laryngeal and vascular toxicity, and expected potential impact on cerebrovascular events.

Evolutionary impact assessment: accounting for evolutionary consequences of fishing in an ecosystem approach to fisheries management

Managing fisheries resources to maintain healthy ecosystems is one of the main goals of the ecosystem approach to fisheries (EAF). While a number of international treaties call for the implementation of EAF, there are still gaps in the underlying methodology. One aspect that has received substantial scientific attention recently is fisheries-induced evolution (FIE). Increasing evidence indicates that intensive fishing has the potential to exert strong directional selection on life-history traits, behaviour, physiology, and morphology of exploited fish. Of particular concern is that reversing evolutionary responses to fishing can be much more difficult than reversing demographic or phenotypically plastic responses. Furthermore, like climate change, multiple agents cause FIE, with effects accumulating over time. Consequently, FIE may alter the utility derived from fish stocks, which in turn can modify the monetary value living aquatic resources provide to society. Quantifying and predicting the evolutionary effects of fishing is therefore important for both ecological and economic reasons. An important reason this is not happening is the lack of an appropriate assessment framework. We therefore describe the evolutionary impact assessment (EvoIA) as a structured approach for assessing the evolutionary consequences of fishing and evaluating the predicted evolutionary outcomes of alternative management options. EvoIA can contribute to EAF by clarifying how evolution may alter stock properties and ecological relations, support the precautionary approach to fisheries management by addressing a previously overlooked source of uncertainty and risk, and thus contribute to sustainable fisheries.

Impact of salt on cardiac differential gene expression and coronary lesion in normotensive mineralocorticoid-treated mice.

We previously reported that excess of deoxycorticosterone-acetate (DOCA)/salt-induced cardiac hypertrophy in the absence of hypertension in one-renin gene mice. This model allows us to study molecular mechanisms of high-salt intake in the development of cardiovascular remodeling, independently of blood pressure in a high mineralocorticoid state. In this study, we compared the effect of 5-wk low- and high-salt intake on cardiovascular remodeling and cardiac differential gene expression in mice receiving the same amount of DOCA. Differential gene and protein expression was measured by high-density cDNA microarray assays, real-time PCR and Western blot analysis in DOCA-high salt (HS) vs. DOCA-low salt (LS) mice. DOCA-HS mice developed cardiac hypertrophy, coronary perivascular fibrosis, and left ventricular dysfunction. Differential gene and protein expression demonstrated that high-salt intake upregulated a subset of genes encoding for proteins involved in inflammation and extracellular matrix remodeling (e.g., Col3a1, Col1a2, Hmox1, and Lcn2). A major subset of downregulated genes encoded for transcription factors, including myeloid differentiation primary response (MyD) genes. Our data provide some evidence that vascular remodeling, fibrosis, and inflammation are important consequences of a high-salt intake in DOCA mice. Our study suggests that among the different pathogenic factors of cardiac and vascular remodeling, such as hypertension and mineralocorticoid excess and sodium intake, the latter is critical for the development of the profibrotic and proinflammatory phenotype observed in the heart of normotensive DOCA-treated mice.

Impact of iron supplementation on substantial unexplained fatigue in iron deficient but not anaemic menstruated women

Aim: To determine the impact of iron therapy on the quality of life of non-anaemic iron-deficient women with substantial unexplained fatigue. Methods: Double blind randomised placebo controlled trial in 198 women aged 18 to 53 and having a ferritin level <50 ng/mL, assigned to either oral ferrous sulphate (80 mg/day of elemental iron daily; n = 102) or placebo (n = 96) for 12 weeks, by 44 general practices in France. Main outcome measures: Level of fatigue, depression and anxiety, measured by a 24-item self-administered questionnaire. Level of fatigue was also assessed with a visual analogue scale. Results: 171 (86.4%) women were eligible for efficacy analysis. Mean age, haemoglobin concentration, serum ferritin concentration, level of fatigue, depression, and anxiety were similar in both groups at baseline. Both groups were also similar for compliance and dropout rates. After 12 weeks, asthenia score decreased by −12.9 } 10.37 points (50.8%) in the iron group compared with -9.01 } 11.71 points (36.7%) in the placebo group (p = 0.02), whereas depression and anxiety scores, already low at inclusion, slightly decrease to the same extent in both groups. In an intention to treat analysis, by considering a responder to iron supplementation as having more than two points decrease on the fatigue 10-point visual analogue scale, iron group had 83,3% (85/102) responders vs. 69.8% (67/96) in the control group (p = 0.02). The number needed to treat to have a benefit was 7. Conclusion: Iron supplementation is an efficient inexpensive approach to manage unexplained fatigue in non-anaemic iron-deficient women.

Impact of recommendation updates in well-controlled patients on nonrecommended antiretroviral therapies: the Swiss HIV cohort study.

BACKGROUND: HIV treatment recommendations are updated as clinical trials are published. Whether recommendations drive clinicians to change antiretroviral therapy in well-controlled patients is unexplored. METHODS: We selected patients with undetectable viral loads (VLs) on nonrecommended regimens containing double-boosted protease inhibitors (DBPIs), triple-nucleoside reverse transcriptase inhibitors (NRTIs), or didanosine (ddI) plus stavudine (d4T) at publication of the 2006 International AIDS Society recommendations. We compared demographic and clinical characteristics with those of control patients with undetectable VL not on these regimens and examined clinical outcome and reasons for treatment modification. RESULTS: At inclusion, 104 patients were in the DBPI group, 436 in the triple-NRTI group, and 19 in the ddI/d4T group. By 2010, 28 (29%), 204 (52%), and 1 (5%) patient were still on DBPIs, triple-NRTIs, and ddI plus d4T, respectively. 'Physician decision,' excluding toxicity/virological failure, drove 30% of treatment changes. Predictors of recommendation nonobservance included female sex [adjusted odds ratio (aOR) 2.69, 95% confidence interval (CI) 1 to 7.26; P = 0.01] for DPBIs, and undetectable VL (aOR 3.53, 95% CI 1.6 to 7.8; P = 0.002) and lack of cardiovascular events (aOR 2.93, 95% CI 1.23 to 6.97; P = 0.02) for triple-NRTIs. All patients on DBPIs with documented diabetes or a cardiovascular event changed treatment. Recommendation observance resulted in lower cholesterol values in the DBPI group (P = 0.06), and more patients having undetectable VL (P = 0.02) in the triple-NRTI group. CONCLUSION: The physician's decision is the main factor driving change from nonrecommended to recommended regimens, whereas virological suppression is associated with not switching. Positive clinical outcomes observed postswitch underline the importance of observing recommendations, even in well-controlled patients.

Meeting highlights of the 8th Annual Scientific Sessions of the Society For Cardiovascular Magnetic Resonance, January 21 to 23, 2005.

Parallel tracks for clinical scientists, basic scientists, and pediatric imagers was the novel approach taken for the highly successful 8th Annual Scientific Sessions of the Society for Cardiovascular Magnetic Resonance, held in San Francisco, California, January 21 to 23, 2005. Attendees were immersed in information on the latest scientific advances in cardiovascular magnetic resonance (CMR) from mice to man and technological advances from systems with field strengths from 0.5 T to 11.7 T. State-of-the-art applications were reviewed, spanning a wide range from molecular imaging to predicting outcome with CMR in large patient populations.

The impact of information on decision-making in palliative care

Résumé Ce travail vise à clarifier les résultats contradictoires de la littérature concernant les besoins des patients d'être informés et de participer à la prise de décision. La littérature insiste sur le contenu de l'information comme base de la prise de décision, bien qu'il existe des preuves que d'autres contenus sont importants pour les patients. La thèse essaie en outre d'identifier des possibilités de mieux répondre aux préférences d'information et de participation des patients. Les travaux ont porté en particulier sur les soins palliatifs. Une analyse de la littérature donne un aperçu sur les soins palliatifs, sur l'information des patients et sur leur participation à la prise de décisions thérapeutiques. Cette analyse résume les résultats d'études précédentes et propose un: modèle théorique d'information, de prise de décision et de relation entre ces deux domaines. Dans le cadre de ce travail, deux études empiriques ont utilisé des questionnaires écrits adressés à des personnes privées et à des professionnels de la santé, couvrant la Suisse et le Royaume Uni, pour identifier d'éventuelles différences entre ces deux pays. Les enquêtes ont été focalisées sur des patients souffrant de cancer du poumon. Les instruments utilisés pour ces études proviennent de la littérature afin de les rendre comparables. Le taux de réponse aux questionnaires était de 30-40%. La majorité des participants aux enquêtes estime que les patients devraient: - collaborer à la prise de décision quant à leur traitement - recevoir autant d'information que possible, positive aussi bien que négative - recevoir toutes les informations mentionnées dans le questionnaire (concernant la maladie, le diagnostic et les traitements), tenant compte de la diversité des priorités des patients - être soutenus par des professionnels de la santé, leur famille, leurs amis et/ou les personnes souffrant de la même maladie En plus, les participants aux enquêtes ont identifié divers contenus de l'information aux patients souffrant d'une maladie grave. Ces contenus comprennent entre autres: - L'aide à la prise de décision concernant le traitement - la possibilité de maintenir le contrôle de la situation - la construction d'une relation entre le patient et le soignant - l'encouragement à faire des projets d'avenir - l'influence de l'état émotionnel - l'aide à la compréhension de la maladie et de son impact - les sources potentielles d'états confusionnels et d'états anxieux La plupart des contenus proposés sont positifs. Les résultats suggèrent la coexistence possible de différents contenus à un moment donné ainsi que leur changement au cours du temps. Un modèle est ensuite développé et commenté pour présenter le diagnostic d'une maladie grave. Ce modèle est basé sur la littérature et intègre les résultats des études empiriques réalisées dans le cadre de ce travail. Ce travail analyse également les sources préférées d'information et de soutien, facteurs qui peuvent influencer ou faire obstacle aux préférences d'information et de participation. Les deux groupes de participants considèrent les médecins spécialistes comme la meilleure source d'information. En ce qui concerne le soutien, les points de vue divergent entre les personnes privées et les professionnels de la santé: généralement, les rôles de soutien semblent peu définis parmi les professionnels. Les barrières à l'information adéquate du patient apparaissent fréquemment liées aux caractéristiques des professionnels et aux problèmes d'organisation. Des progrès dans ce domaine contribueraient à améliorer les soins fournis aux patients. Finalement, les limites des études empiriques sont discutées. Celles-ci comprennent, entre autres, la représentativité restreinte des participants et les objections de certains groupes de participants à quelques détails des questionnaires. Summary The present thesis follows a call from the current body of literature to better understand patient needs for information and for participation in decision-making, as previous research findings had been contradictory. Information so far seems to have been considered essentially as a means to making treatment decisions, despite certain evidence that it may have a number of other values to patients. Furthermore, the thesis aims to identify ways to optimise meeting patient preferences for information and participation in treatment decisions. The current field of interest is palliative care. An extensive literature review depicts the background of current concepts of palliative care, patient information and patient involvement into treatment decisions. It also draws together results from previous studies and develops a theoretical model of information, decision-making, and the relationship between them. This is followed by two empirical studies collecting data from members of the general public and health care professionals by means of postal questionnaires. The professional study covers both Switzerland and the United Kingdom in order to identify possible differences between countries. Both studies focus on newly diagnosed lung cancer patients. The instruments used were taken from the literature to make them comparable. The response rate in both surveys was 30-40%, as expected -sufficient to allow stastical tests to be performed. A third study, addressed to lung cancer patients themselves, turned out to require too much time within the frame available. A majority of both study populations thought that patients should: - have a collaborative role in treatment-related decision-making -receive as much information as possible, good or bad - receive all types of information mentioned in the questionnaire (about illness, tests, and treatment), although priorities varied across the study populations - be supported by health professionals, family members, friends and/or others with the same illness Furthermore they identified various 'meanings' information may have to patients with a serious illness. These included: - being an aid in treatment-related decision-making - allowing control to be maintained over the situation - helping the patient-professional relationship to be constructed - allowing plans to be made - being positive for the patient's emotional state - helping the illness and its impact to be understood - being a source of anxiety - being a potential source of confusion to the patient Meanings were mostly positive. It was suggested that different meanings could co-exist at a given time and that they might change over time. A model of coping with the disclosure of a serious diagnosis is then developped. This model is based on existing models of coping with threatening events, as takeñ from the literature [ref. 77, 78], and integrates findings from the empirical studies. The thesis then analyses the remaining aspects apparent from the two surveys. These range from the identification of preferred information and support providers to factors influencing or impeding information and participation preferences. Specialist doctors were identified by both study populations as the best information providers whilst with regard to support provision views differed between the general public and health professionals. A need for better definition of supportive roles among health care workers seemed apparent. Barriers to information provision often seem related to health professional characteristics or organisational difficulties, and improvements in the latter field could well help optimising patient care. Finally, limitations of the studies are discussed, including questions of representativness of certain results and difficulties with or objections against questionnaire details by some groups of respondents.