Introduction L’insuline basale peglispro (BIL ; LY2605541) est une nouvelle insuline lispro PEGylée de grande taille hydrodynamique. BIL est une insuline à durée d’action prolongée. La population des ...patients DT1 et DT2 pouvant inclure des patients insuffisants hépatiques, la pharmacocinétique de BIL a été comparée entre sujets présentant différents degrés d’insuffisance hépatique (IH) et sujets sains. Matériels et méthodes Dans cette étude ouverte en groupes parallèles, 35 sujets ont reçu une dose SC unique de 0,33 U/kg. Les prélèvements sanguins ont été recueillis jusqu’à 9 jours. La pharmacocinétique de BIL a été déterminée pendant 9 jours post-dose avec un ELISA spécifique. Les paramètres pharmacocinétiques ont été calculés en utilisant des analyses non compartimentales. Résultats Trente-cinq sujets ont été évalués (12 sujets sains ; 8 IH légère, 8 modérée, 7 sévère, selon les critères de Child-Pugh). Les sujets étaient non diabétiques sauf un DT2, 57 % d’hommes, 41-69 ans, IMC moyen (ET) 27,7 (4,52) kg/m². Les sujets sains ont été appariés à des sujets IH pour l’âge, le poids et le sexe. Les ratios des moyennes géométriques MC et des IC90 % pour l’ASC (0-∞) des sujets IH légère, modérée et sévère sur les sujets sains étaient de 0,789 (0,556 ; 1,12), 0,744 (0,525 ; 1,06) et 0,782 (0,543 ; 1,12), respectivement. Les ratios (IC90 %) pour Cmax étaient de 0,728 (0,398 ; 1,33), 0,905 (0,495 ; 1,65) et 0,840 (0,448 ; 1,58), respectivement. Le temps médian de Cmax et la demi-vie moyenne étaient similaires entre les groupes. Les sujets sains et les sujets IH ont signalé chacun 7 événements indésirables (majoritairement légers). Conclusion Les doses uniques de BIL étaient bien tolérées chez les sujets IH et sains. Un chevauchement important de l’ASC moyenne (0-∞) et de la Cmax a été observé entre les groupes et les ratios sujets IH/sujets sains n’étaient pas statistiquement différents. D’après ces données, un ajustement des doses de BIL ne semble pas nécessaire chez les sujets IH. Déclaration d’intérêt Les auteurs déclarent avoir un intérêt avec un organisme privé, industriel ou commercial en relation avec le sujet présenté. S.L. Choi, C. Loghin, P. Garhyan, M.P. Knadler, E. Lam, V. Sinha, N. Porksen, H. Linnebjerg: salariés de Eli Lilly. V. Sinha: former employee of Eli Lilly and Company, a current shareholder, and has a patent pending for LY2605541 (Eli Lilly and Company is the assignee).
When a parametric likelihood function is not specified for a model, estimating equations may provide an instrument for statistical inference. Qin and Lawless (1994) illustrated that empirical ...likelihood makes optimal use of these equations in inferences for fixed low-dimensional unknown parameters. In this paper, we study empirical likelihood for general estimating equations with growing high dimensionality and propose a penalized empirical likelihood approach for parameter estimation and variable selection. We quantify the asymptotic properties of empirical likelihood and its penalized version, and show that penalized empirical likelihood has the oracle property. The performance of the proposed method is illustrated via simulated applications and a data analysis.
Abdominal aortic aneurysm (AAA) is found in 5% to 10% of men aged 65 to 79 years. The major complication is rupture which presents as a surgical emergency. The mortality after rupture is high, 80% ...for patients reaching hospital and 50% for those undergoing surgery for emergency repair. Currently elective surgical repair is recommended for aneurysms discovered to be larger than 5.5 cm to prevent rupture. There is interest in population screening to detect, monitor and repair abdominal aortic aneurysms before rupture.
To determine the effects of screening asymptomatic individuals for AAA on mortality, subsequent treatment, quality of life and cost effectiveness of screening.
The Cochrane Peripheral Vascular Diseases Group searched their Trials Register (last searched 26 January 2007) and CENTRAL (last searched Issue 1, 2007).
Randomised controlled trials of population screening for AAA.
Two authors independently assessed trials and extracted data.
Four studies involving 127,891 men and 9,342 women were included in this review. Only one study included women. Results for men and women were analysed separately. Three to five years after screening there was no significant difference in all-cause mortality between screened and unscreened groups for men or women (men, odds ratio (OR) 0.95; 95% Confidence interval (CI) 0.85 to 1.07; for women OR 1.06; 95% CI 0.93 to 1.21). There was a significant decrease in mortality from AAA in men (OR 0.60; 95% CI 0.47 to 0.78), but not for women (OR 1.99; 95% CI 0.36 to 10.88). In this analysis mortality includes death from rupture and from emergency or elective surgery for aneurysm repair. There was also a decreased incidence of ruptured aneurysm in men (OR 0.45; 95% CI 0.21 to 0.99) but not in women (OR 1.49; 95% CI 0.25 to 8.94). There was a significant increase in surgery for AAA in men (OR 2.03; 95% CI 1.59 to 2.59). This was not reported in women. There were no data on life expectancy, complications of surgery or subjective quality of life.
There is evidence of a significant reduction in mortality from AAA in men aged 65 to 79 years who undergo ultrasound screening. There is insufficient evidence to demonstrate benefit in women. The cost effectiveness may be acceptable, but needs further expert analysis. These findings need careful consideration in judging whether a co-ordinated population-based screening programme should be introduced.
The temperature-dependent (T-dependent) linewidth (ΓG) and frequency shift (ΔωG) of the G mode provide valuable information on the phonon anharmonicity of graphene-based materials. In contrast to the ...negligible contribution from electron-phonon coupling (EPC) to the linewidth of a Raman mode in semiconductors, ΓG in pristine graphene is dominated by EPC contribution at room temperature due to its semimetallic characteristics. This leads to difficulty in resolving intrinsic contribution from phonon anharmonicity to ΓG. Here, we probed the intrinsic phonon anharmonicity of heavily-doped graphene by T-dependent Raman spectra based on FeCl3-based stage-1 graphite intercalation compound (GIC), in which the EPC contribution is negligible due to the large Fermi level (EF) shift. The ΔωG and ΓG exhibit a nonlinear decrease and noticeable broadening with increasing temperature, respectively, which are both dominated by phonon anharmonicity processes. The contribution of phonon anharmonicity to ΓG of heavily-doped graphene decreases as the EF approaches to the Dirac point. However, the T dependence of ΔωG is almost independent on EF and qualitatively agrees with the theoretical result of pristine graphene. These results provide a deeper understanding of the role of phonon anharmonicity on the Raman spectra of heavily doped graphene.
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Lipid-lowering therapy is recommended for secondary prevention in people with coronary artery disease. It may also reduce cardiovascular events and/or local disease progression in people with lower ...limb peripheral arterial disease (PAD).
To assess the effects of lipid-lowering therapy on all-cause mortality, cardiovascular events and local disease progression in patients with PAD of the lower limb.
The authors searched The Cochrane Peripheral Vascular Diseases Group's Specialised Register (last searched February 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 2, 2007) for publications describing randomised controlled trials of lipid-lowering therapy in peripheral arterial disease of the lower limb.
Randomised controlled trials of lipid-lowering therapy in patients with PAD of the lower limb.
Three authors independently assessed trial quality and extracted data.
Eighteen trials were included, involving a total of 10,049 participants. Trials differed considerably in their inclusion criteria, outcomes measured, and type of lipid-lowering therapy used. Only one trial (PQRST) reported a detrimental effect of active treatment on blood lipid/lipoprotein levels. The pooled results from all eligible trials indicated that lipid-lowering therapy had no statistically significant effect on overall mortality (Odds Ratio (OR) 0.86; 95% Confidence Interval (CI) 0.49 to 1.50) or on total cardiovascular events (OR 0.8; 95% CI 0.59 to 1.09). However, subgroup analysis which excluded PQRST showed that lipid-lowering therapy significantly reduced the risk of total cardiovascular events (OR 0.74; CI 0.55 to 0.98). This was primarily due to a positive effect on total coronary events (OR 0.76; 95% CI 0.67 to 0.87). Greatest evidence of effectiveness came from the use of simvastatin in people with a blood cholesterol >/= 3.5 mmol/litre (HPS). Pooling of the results from several small trials on a range of different lipid-lowering agents indicated an improvement in total walking distance (Weighted Mean Difference (WMD) 152 m; 95% CI 32.11 to 271.88) and pain-free walking distance (WMD 89.76 m; 95% CI 30.05 to 149.47) but no significant impact on ankle brachial index (WMD 0.04; 95% CI -0.01 to 0.09).
Lipid-lowering therapy is effective in reducing cardiovascular mortality and morbidity in people with PAD. It may also improve local symptoms. Until further evidence on the relative effectiveness of different lipid-lowering agents is available, use of a statin in people with PAD and a blood cholesterol level >/=3.5 mmol/litre is most indicated.
The coronavirus disease 2019 (COVID-19) pandemic presented unprecedented challenges for healthcare systems worldwide. The Queen Elizabeth Hospital, Birmingham, has one of the largest burns, hands and ...plastics department in the UK, totalling 83 doctors. Our response to the COVID-19 response was uniquely far reaching, with our department being given responsibility of an entire 36 bed medical COVID-19 ward in addition to our commitment to specialty-specific work, and saw half of our work force re-deployed to Intensive Treatment Unit (ITU). Our aim was to exploit the high calibre of doctors found in plastic surgery, and to demonstrate, we were able to support the COVID-19 effort beyond our normal scope of practice.
In order to achieve this aim, the department underwent significant structural and leadership changes. Factors considered included: rota and shift pattern changes to implement depth and resilience to sudden fluctuations in staffing levels; a preparatory phase for focussed upskilling and relevant training packages to be delivered; managing the COVID-19 ward cover and ITU deployment; adjustments to our front of house and elective specialty-specific service, including developing alternative and streamlined patient pathways; mitigating the effects on plastic surgical training during the pandemic; the importance of communications for patient care and physician wellbeing; and leadership techniques and styles we considered important.
By sharing our experience during this pandemic, we hope to reflect on and share lessons learned, as well as to demonstrate that it is possible to rapidly mobilise and retrain plastic surgeons at all levels to contribute safely and productively beyond a specialty-specific scope of care.
This study assessed the prevalence and predictors of food insecurity among a cohort of underserved oncology patients at New York City cancer clinics. A demographic survey and the U.S. Household Food ...Security Survey Module were administered. A multivariate General Linear Model Analysis of Covariance was used to evaluate predictors of food insecurity. Four hundred and four (404) completed the surveys. Nearly one-fifth (18%) had very low, 38% low, 17% marginal, and 27% high food security. The Analysis of Covariance was statistically significant (F7, 370 = 19.08; p < .0001; R-Square = 0.26). Younger age, Spanish language, poor health care access, and having less money for food since beginning cancer treatment were significantly associated with greater food insecurity. This cohort of underserved cancer patients had rates of food insecurity nearly five times those of the state average. More research is needed to understand better the causes and impact of food insecurity among cancer and chronic disease patients.
Exercise programmes are a relatively inexpensive, low-risk option compared with other, more invasive therapies for treatment of leg pain on walking (intermittent claudication (IC)). This is the ...fourth update of a review first published in 1998.
Our goal was to determine whether an exercise programme was effective in alleviating symptoms and increasing walking treadmill distances and walking times in people with intermittent claudication. Secondary objectives were to determine whether exercise was effective in preventing deterioration of underlying disease, reducing cardiovascular events, and improving quality of life.
For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (last searched 15 November 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10) via the Cochrane Register of Studies Online, along with trials registries.
Randomised controlled trials of an exercise regimen versus control or versus medical therapy for people with IC due to peripheral arterial disease (PAD). We included any exercise programme or regimen used for treatment of IC, such as walking, skipping, and running. Inclusion of trials was not affected by duration, frequency, or intensity of the exercise programme. Outcome measures collected included treadmill walking distance (time to onset of pain or pain-free walking distance and maximum walking time or maximum walking distance), ankle brachial index (ABI), quality of life, morbidity, or amputation; if none of these was reported, we did not include the trial in this review.
For this update (2017), RAL and AH selected trials and extracted data independently. We assessed study quality by using the Cochrane 'Risk of bias' tool. We analysed continuous data by determining mean differences (MDs) and 95% confidence intervals (CIs), and dichotomous data by determining risk ratios (RRs) and 95% CIs. We pooled data using a fixed-effect model unless we identified significant heterogeneity, in which case we used a random-effects model. We used the GRADE approach to assess the overall quality of evidence supporting the outcomes assessed in this review.
We included two new studies in this update and identified additional publications for previously included studies, bringing the total number of studies meeting the inclusion criteria to 32, and involving a total of 1835 participants with stable leg pain. The follow-up period ranged from two weeks to two years. Types of exercise varied from strength training to polestriding and upper or lower limb exercises; supervised sessions were generally held at least twice a week. Most trials used a treadmill walking test for one of the primary outcome measures. The methodological quality of included trials was moderate, mainly owing to absence of relevant information. Most trials were small and included 20 to 49 participants. Twenty-seven trials compared exercise versus usual care or placebo, and the five remaining trials compared exercise versus medication (pentoxifylline, iloprost, antiplatelet agents, and vitamin E) or pneumatic calf compression; we generally excluded people with various medical conditions or other pre-existing limitations to their exercise capacity.Meta-analysis from nine studies with 391 participants showed overall improvement in pain-free walking distance in the exercise group compared with the no exercise group (MD 82.11 m, 95% CI 71.73 to 92.48, P < 0.00001, high-quality evidence). Data also showed benefit from exercise in improved maximum walking distance (MD 120.36 m, 95% CI 50.79 to 189.92, P < 0.0007, high-quality evidence), as revealed by pooling data from 10 studies with 500 participants. Improvements were seen for up to two years.Exercise did not improve the ABI (MD 0.04, 95% CI 0.00 to 0.08, 13 trials, 570 participants, moderate-quality evidence). Limited data were available for the outcomes of mortality and amputation; trials provided no evidence of an effect of exercise, when compared with placebo or usual care, on mortality (RR 0.92, 95% CI 0.39 to 2.17, 5 trials, 540 participants, moderate-quality evidence) or amputation (RR 0.20, 95% CI 0.01 to 4.15, 1 trial, 177 participants, low-quality evidence).Researchers measured quality of life using Short Form (SF)-36 at three and six months. At three months, the domains 'physical function', 'vitality', and 'role physical' improved with exercise; however this was a limited finding, as it was reported by only two trials. At six months, meta-analysis showed improvement in 'physical summary score' (MD 2.15, 95% CI 1.26 to 3.04, P = 0.02, 5 trials, 429 participants, moderate-quality evidence) and in 'mental summary score' (MD 3.76, 95% CI 2.70 to 4.82, P < 0.01, 4 trials, 343 participants, moderate-quality evidence) secondary to exercise. Two trials reported the remaining domains of the SF-36. Data showed improvements secondary to exercise in 'physical function' and 'general health'. The other domains - 'role physical', 'bodily pain', 'vitality', 'social', 'role emotional', and 'mental health' - did not show improvement at six months.Evidence was generally limited in trials comparing exercise versus antiplatelet therapy, pentoxifylline, iloprost, vitamin E, and pneumatic foot and calf compression owing to small numbers of trials and participants.Review authors used GRADE to assess the evidence presented in this review and determined that quality was moderate to high. Although results showed significant heterogeneity between trials, populations and outcomes were comparable overall, with findings relevant to the claudicant population. Results were pooled for large sample sizes - over 300 participants for most outcomes - using reproducible methods.
High-quality evidence shows that exercise programmes provided important benefit compared with placebo or usual care in improving both pain-free and maximum walking distance in people with leg pain from IC who were considered to be fit for exercise intervention. Exercise did not improve ABI, and we found no evidence of an effect of exercise on amputation or mortality. Exercise may improve quality of life when compared with placebo or usual care. As time has progressed, the trials undertaken have begun to include exercise versus exercise or other modalities; therefore we can include fewer of the new trials in this update.
We propose a novel quantile regression approach for longitudinal data analysis which naturally incorporates auxiliary information from the conditional mean model to account for within-subject ...correlations. The efficiency gain is quantified theoretically and demonstrated empirically via simulation studies and the analysis of a real dataset.
Measurements of cloud condensation nuclei (CCN), condensation nuclei (CN) and aerosol chemical composition were performed simultaneously at an urban site in Shanghai from 6 to 9 November 2010. The ...variations of CCN number concentration (NCCN) and aerosol activity (activated aerosol fraction, NCCN/NCN) were examined during a fog–haze co-occurring event. Anthropogenic pollutants emitted from vehicles and unfavorable meteorological conditions such as low planetary boundary layer (PBL) height exerted a great influence on PM2.5 and black carbon (BC) loadings. NCCN at 0.2% supersaturation (SS) mostly fell in the range of 994 to 6268 cm−3, and the corresponding NCCN/NCN varied between 0.09 and 0.57. NCCN and NCCN/NCN usually were usually higher in the hazy case due to increased aerosol concentration in the accumulation mode (100–500 nm), and lower in the foggy–hazy and clear cases. The BC mass concentration posed a strong positive effect on NCCN in the foggy–hazy and hazy cases, whereas it poorly correlated with NCCN in the clear case. NCCN/NCN was weakly related with BC in both foggy–hazy and hazy cases. By using a simplified particle hygroscopicity (κ), the calculated critical dry size (CDS) of activated aerosol did not exceed 130 nm at 0.2% SS in spite of diverse aerosol chemical compositions. The predicted NCCN at 0.2% SS was very successful compared with the observed NCCN in clear case (R2=0.96) and foggy–hazy/hazy cases (R2=0.91). In addition, their corresponding ratios of predicted to observed NCCNwere on average 0.95 and 0.92, respectively. More organic matter is possibly responsible for this closure difference between foggy–hazy/hazy and clear cases. These results reveal that the particulate pollutant burden exerts a significant impact on NCCN, especially NCCN/NCN promotes effectively during the polluted periods.
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