Effect of oxygen versus adaptive pressure support servo-ventilation in patients with central sleep apnoea-Cheyne Stokes respiration and congestive heart failure.

BACKGROUND AND AIMS: Central sleep apnoea with Cheyne-Stokes respiration (CSA-CSR) is a common, serious consequence of congestive heart failure. Optimal treatment is yet to be established. We compared two common treatments for CSA-CSR. METHODS: Subjects with CSA-CSR and stable congestive heart failure were randomised to 8 weeks treatment: oxygen 2 L/min through nasal prongs and concentrator or 8 weeks adaptive servo-ventilation (ASV) using a crossover design separated by a 3-week washout. Polysomnography, indices of sleep and breathing, shuttle walk distance, symptoms, urinary catecholamines, plasma brain natriuretic peptide (NT-BNP) and echocardiography were collected at baseline and completion of each arm. RESULTS: Ten subjects (age 64 ± 10 years, left ventricular ejection fraction (LVEF) 28 ± 10.5%, apnoea-hypopnoea index (AHI) 63 ± 30/h) were recruited. Seven completed the protocol (one died, one refused ASV, one was withdrawn after hospital admission). On therapy, an AHI of < 10/h was achieved in two out of seven using oxygen (29%), six of seven using ASV (86%) and six of seven with either (86%). Compliance with ASV: 5.2 ± 2 h/night (range 1.45-7.1 h/night). Median AHI on oxygen therapy: 13.4 /h (range 2.6-42.9/h), ASV, 1.4 /h (range 0.6-17.8/h, P = 0.03). LVEF was not changed by either therapy (oxygen 30.9% vs 30.9% P = 0.97, ASV 32.5% vs 35.0% P = 0.24). NT-BNP, urinary catecholamines, shuttle walk distance and symptoms were not significantly changed by either therapy. CONCLUSION: CSA-CSR is reduced to a greater extent by ASV than oxygen therapy over 8 weeks but was not accepted long term. Neither treatment improved prognostic indices of heart failure or symptoms in the short term.

Effectiveness and toxicity of lenvatinib in refractory thyroid cancer: Dutch real-life data.

OBJECTIVE: The SELECT trial showed progression-free survival (PFS) benefit for lenvatinib for advanced radioiodine-refractory differentiated thyroid cancer (RAI-refractory or RR-DTC) patients, on which current clinical practice is based. We assessed whether the effectiveness and toxicity of lenvatinib in real-life clinical practice in the Netherlands were comparable to the pivotal SELECT trial. METHODS: From three Dutch centres Electronic Health Records (EHRs) of patients treated in the lenvatinib compassionate use program or as standard of care were reviewed and checked for SELECT eligibility criteria. Baseline characteristics, safety, and efficacy measures were compared and PFS and overall survival (OS) were calculated. Furthermore, PFS was compared to estimates of PFS reported in other studies. RESULTS: A total of 39 DTC patients with a median age of 62 years were analysed. Of these, 27 patients (69%) did not fulfil the SELECT eligibility criteria. The most common grade ≥3 toxicities were hypertension (n = 11, 28%), diarrhoea (n = 7, 18%), vomiting (n = 4, 10%), and gallbladder disease (n = 3, 8%). Median PFS and median OS were 9.7 (95% confidence interval (CI): 4.0-15.5) and 18.3 (95% CI: 4.9-31.7) months, respectively, response rate was 38% (95% CI: 23-54%). PFS in the Dutch real-life situation was comparable to previous real-life studies, but inferior to PFS as shown in the SELECT trial (P = 0.04). CONCLUSIONS: PFS in our non-trial population was significantly shorter than in the SELECT trial population. In the interpretation of results, differences in the real-life population and the SELECT study population regarding patient characteristics should be taken into account.

Landslides on Ceres: Diversity and Geologic Context.

Landslides are among the most widespread geologic features on Ceres. Using data from Dawn's Framing Camera, landslides were previously classified based upon geomorphologic characteristics into one of three archetypal categories, Type 1(T1), Type 2 (T2), and Type 3 (T3). Due to their geologic context, variation in age, and physical characteristics, most landslides on Ceres are, however, intermediate in their morphology and physical properties between the archetypes of each landslide class. Here we describe the varied morphology of individual intermediate landslides, identify geologic controls that contribute to this variation, and provide first-order quantification of the physical properties of the continuum of Ceres's surface flows. These intermediate flows appear in varied settings and show a range of characteristics, including those found at contacts between craters, those having multiple trunks or lobes; showing characteristics of both T2 and T3 landslides; material slumping on crater rims; very small, ejecta-like flows; and those appearing inside of catenae. We suggest that while their morphologies can vary, the distribution and mechanical properties of intermediate landslides do not differ significantly from that of archetypal landslides, confirming a link between landslides and subsurface ice. We also find that most intermediate landslides are similar to Type 2 landslides and formed by shallow failure. Clusters of these features suggest ice enhancement near Juling, Kupalo and Urvara craters. Since the majority of Ceres's landslides fall in the intermediate landslide category, placing their attributes in context contributes to a better understanding of Ceres's shallow subsurface and the nature of ground ice.

Continuous positive airway pressure in heart failure patients with obstructive sleep apnoea.

BACKGROUND: The aim of the study was to study the effect of 6 months of continuous positive airway pressure (CPAP) in community heart failure (HF) patients with obstructive sleep apnoea (OSA). METHODS: Clinically stable outpatients with HF and OSA (left ventricular ejection fraction (LVEF) <45%, apnoea/hypopnoea index >15/h, n = 19) treated with CPAP and a control group (LVEF <45%, apnoea/hypopnoea index <10/h, n = 7) were compared at baseline and at 6 months by Minnesota heart failure score, Epworth sleepiness score, shuttle walk distance, brain natriuretic peptide, urinary catecholamines and echocardiographic indices using paired t-test, McNemar's tests and effect sizes. RESULTS: In HF patients with OSA, CPAP improved LVEF (35.9 +/- 6.1% to 40.6 +/- 8.0%, P = 0.015), decreased LV end-systolic volume (152 +/- 74 to 135 +/- 62 cm(3), P = 0.03), systolic blood pressure (P = 0.04) and sleepiness (Epworth sleepiness score 8.8 +/- 4.8 to 6.3 +/- 3.2, P = 0.01), whereas walk distance, catecholamines, brain natriuretic peptide levels and symptoms were unchanged. These outcomes did not change in the HF control group. CONCLUSION: In community HF patients with OSA, CPAP therapy over 6 months improved LVEF, systolic blood pressure and sleepiness, but not sympathetic activation, brain natriuretic peptide or exercise levels. Acceptance was relatively low, potentially limiting therapeutic effectiveness.

Analysis of the regional pulse wave velocity by Doppler: methodology and reproducibility.

Increased arterial stiffness is observed in a number of cases. The analysis of the regional functional arterial properties is of interest to determine the role of a given risk factor on the vascular wall and in some diseases such as atherosclerosis. We analysed the pulse wave velocity (PWV) measured by the Doppler method with 2D guidance and its reproducibility in different arterial segments in 15 men with coronary artery disease. Regional Doppler PWV was defined as the distance between the extremities of a given segment divided by the transit time calculated by Doppler. Intra- and interobserver reproducibilities of the Doppler measurements were studied in all of the subjects. The variation coefficients were low, maximum at the level of ascending aorta and minimal at the level of iliac segment. This good reproducibility was validated by the Bland-Altman method. Moreover, using this Doppler technique, we found a progressive increase in PWV from the ascending aorta to the iliac segment. These data demonstrate that noninvasive Doppler analysis is a feasible and reproducible method to determine regional PWV.

Preferences of patients for patient centred approach to consultation in primary care: observational study.

OBJECTIVE: To identify patient's preferences for patient centred consultation in general practice. DESIGN: Questionnaire study. SETTING: Consecutive patients in the waiting room of three doctors' surgeries. MAIN OUTCOME MEASURES: Key domains of patient centredness from the patient perspective. Predictors of preferences for patient centredness, a prescription, and examination. RESULTS: 865 patients participated: 824 (95%) returned the pre-consultation questionnaire and were similar in demographic characteristic to national samples. Factor analysis identified three domains of patient preferences: communication (agreed with by 88-99%), partnership (77-87%), and health promotion (85-89%). Fewer wanted an examination (63%), and only a quarter wanted a prescription. As desire for a prescription was modestly associated with desire for good communication (odds ratio 1.20; 95% confidence interval 0.85 to 1.69), partnership (1.46; 1.01 to 2.09), and health promotion (1.61; 1.12 to 2.31) this study may have underestimated preferences for patient centredness compared with populations with stronger preferences for a prescription. Patients who strongly wanted good communication were more likely to feel unwell (very, moderately, and slightly unwell; odds ratios 1, 0.56, 0.39 respectively, z trend P<0.001), be high attenders (1.70; 1.18 to 2.44), and have no paid work (1.84; 1.21 to 2.79). Strongly wanting partnership was also related to feeling unwell, worrying about the problem, high attendance, and no paid work; and health promotion to high attendance and worry. CONCLUSION: Patients in primary care strongly want a patient centred approach, with communication, partnership, and health promotion. Doctors should be sensitive to patients who have a strong preference for patient centredness-those vulnerable either psychosocially or because they are feeling unwell.

Observational study of effect of patient centredness and positive approach on outcomes of general practice consultations.

OBJECTIVE: To measure patients' perceptions of patient centredness and the relation of these perceptions to outcomes. DESIGN: Observational study using questionnaires. SETTING: Three general practices. PARTICIPANTS: 865 consecutive patients attending the practices. MAIN OUTCOME MEASURES: Patients' enablement, satisfaction, and burden of symptoms. RESULTS: Factor analysis identified five components. These were communication and partnership (a sympathetic doctor interested in patients' worries and expectations and who discusses and agrees the problem and treatment, Cronbach's alpha=0.96); personal relationship (a doctor who knows the patient and their emotional needs, alpha=0.89); health promotion (alpha=0.87); positive approach (being definite about the problem and when it would settle, alpha=0.84); and interest in effect on patient's life (alpha=0.89). Satisfaction was related to communication and partnership (adjusted beta=19.1; 95% confidence interval 17.7 to 20.7) and a positive approach (4.28; 2.96 to 5.60). Enablement was greater with interest in the effect on life (0.55; 0.25 to 0.86), health promotion (0.57; 0.30 to 0.85), and a positive approach (0.82; 0.52 to 1.11). A positive approach was also associated with reduced symptom burden at one month (beta=-0.25; -0.41 to -0.10). Referrals were fewer if patients felt they had a personal relationship with their doctor (odds ratio 0.70; 0.54 to 0.90). CONCLUSIONS: Components of patients' perceptions can be measured reliably and predict different outcomes. If doctors don't provide a positive, patient centred approach patients will be less satisfied, less enabled, and may have greater symptom burden and higher rates of referral.

Diet but not aerobic exercise training reduces skeletal muscle TNF-alpha in overweight humans.

AIMS/HYPOTHESIS: Our aim was to test the hypothesis that TNF-alpha protein levels in skeletal muscle are important in mediating the improvements in glucose homeostasis that are associated with diet and exercise regimens intended to reduce cardiovascular risk. METHODS: We recruited 20 people with a body mass index of 32.1 +/- 1.2 kg/m2 (mean +/- SEM) and one other component of the metabolic syndrome. The average age was 51.2 +/- 8.1 years (mean +/- SD). Of the 20 subjects, 6 were men and 14 were women. All subjects completed an 8-week control period, followed by randomisation to 8 weeks of moderate cycling exercise (30 min, three times per week) or to a diet with the following characteristics: low in saturated fat, high in fibre, low glycaemic index, rich in complex carbohydrates. RESULTS: Diet induced a small reduction in body mass index (3.0 +/- 0.7%, p<0.05), although weight loss was not intended. Exercise training increased maximum oxygen consumption by 12 +/- 6% (p<0.05). Both interventions reduced fasting plasma insulin levels by about 20%. Diet reduced skeletal muscle TNF-alpha protein by 54 +/- 10% (p<0.05), an effect that was independent (p=0.94 in covariate analysis) of the small concurrent weight loss (-2.8 +/- 0.7 kg). Levels of GLUT4 protein were unchanged in the diet group. In contrast, exercise training did not significantly change TNF-alpha protein expression, but GLUT4 protein expression increased by 105 +/- 37% (p<0.05). CONCLUSIONS/INTERPRETATION: These data indicate that the metabolic benefits of a diet aimed at cardiovascular risk reduction are associated with a decrease in skeletal muscle TNF-alpha protein.

Aerobic exercise training does not modify large-artery compliance in isolated systolic hypertension.

The present study characterized large-artery properties in patients with isolated systolic hypertension (ISH) and determined the efficacy of exercise training in modifying these properties. Twenty patients (10 male and 10 female) with stage I ISH and 20 age- and gender-matched control subjects were recruited, and large-artery properties were assessed noninvasively. Ten ISH patients (5 male and 5 female) were enrolled in a randomized crossover study comparing 8 weeks of moderate intensity cycling with 8 weeks of sedentary activity. Brachial and carotid systolic, diastolic, mean, and pulse pressures were higher in the ISH group than in the control group. Systemic arterial compliance (0.43+/-0.04 versus 0.29+/-0.02 arbitrary compliance units for the control versus ISH groups, respectively; P=0.01) was lower, and carotid-to-femoral pulse-wave velocity (9.67+/-0.36 versus 11.43+/-0.51 m. s(-1) for the control versus ISH groups, respectively; P=0.007), input impedance (2.39+/-0.19 versus 3.27+/-0.34 mm Hg. s. cm(-1) for the control versus ISH groups, respectively; P=0.04), and characteristic impedance (1.67+/-0.17 versus 2.34+/-0.27 mm Hg. s. cm(-1) for the control versus ISH groups, respectively; P=0.05) were higher in the ISH group than in the control group. Training increased maximal oxygen consumption by 13+/-5% (P=0.04) and maximum workload by 8+/-4% (P=0.05); however, there was no effect on arterial mechanical properties, blood lipids, or left ventricular mass or function. These results suggest that the large-artery stiffening associated with ISH is resistant to modification through short-term aerobic training.