Effect of ramipril on walking times and quality of life among patients with peripheral artery disease and intermittent claudication : a randomized controlled trial

Importance Approximately one-third of patients with peripheral artery disease experience intermittent claudication, with consequent loss of quality of life. Objective To determine the efficacy of ramipril for improving walking ability, patient-perceived walking performance, and quality of life in patients with claudication. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial conducted among 212 patients with peripheral artery disease (mean age, 65.5 [SD, 6.2] years), initiated in May 2008 and completed in August 2011 and conducted at 3 hospitals in Australia. Intervention Patients were randomized to receive 10 mg/d of ramipril (n = 106) or matching placebo (n = 106) for 24 weeks. Main Outcome Measures Maximum and pain-free walking times were recorded during a standard treadmill test. The Walking Impairment Questionnaire (WIQ) and Short-Form 36 Health Survey (SF-36) were used to assess walking ability and quality of life, respectively. Results At 6 months, relative to placebo, ramipril was associated with a 75-second (95% CI, 60-89 seconds) increase in mean pain-free walking time (P < .001) and a 255-second (95% CI, 215-295 seconds) increase in maximum walking time (P < .001). Relative to placebo, ramipril improved the WIQ median distance score by 13.8 (Hodges-Lehmann 95% CI, 12.2-15.5), speed score by 13.3 (95% CI, 11.9-15.2), and stair climbing score by 25.2 (95% CI, 25.1-29.4) (P < .001 for all). The overall SF-36 median Physical Component Summary score improved by 8.2 (Hodges-Lehmann 95% CI, 3.6-11.4; P = .02) in the ramipril group relative to placebo. Ramipril did not affect the overall SF-36 median Mental Component Summary score. Conclusions and Relevance Among patients with intermittent claudication, 24-week treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking times compared with placebo. This was associated with a significant increase in the physical functioning component of the SF-36 score. Trial Registration clinicaltrials.gov Identifier: NCT00681226

Controlling whole blood activation and resultant clot properties by carboxyl and alkyl functional groups on material surfaces : a possible therapeutic approach for enhancing bone healing

Most research virtually ignores the important role of a blood clot in supporting bone healing. In this study, we investigated the effects of surface functional groups carboxyl and alkyl on whole blood coagulation, complement activation and blood clot formation. We synthesised and tested a series of materials with different ratios of carboxyl (–COOH) and alkyl (–CH3, –CH2CH3 and –(CH2)3CH3) groups. We found that surfaces with –COOH/–(CH2)3CH3 induced a faster coagulation activation than those with –COOH/– CH3 and –CH2CH3, regardless of the –COOH ratios. An increase in –COOH ratios on –COOH/–CH3 and –CH2CH3 surfaces decreased the rate of coagulation activation. The pattern of complement activation was entirely similar to that of surface-induced coagulation. All material coated surfaces resulted in clots with thicker fibrin in a denser network at the clot/material interface and a significantly slower initial fibrinolysis when compared to uncoated glass surfaces. The amounts of platelet-derived growth factor-AB (PDGF-AB) and transforming growth factor-b (TGF-b1) released from an intact clot were higher than a lysed clot. The release of PDGF-AB was found to be correlated with the fibrin density. This study demonstrated that surface chemistry can significantly influence the activation of blood coagulation and complement system, resultant clot structure, susceptibility to fibrinolysis as well as release of growth factors, which are important factors determining the bone healing process.

Symptom control and quality of life in lux-lung 3 : a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations

Purpose Patient-reported symptoms and health-related quality of life (QoL) benefits were investigated in a randomized, phase III trial of afatinib or cisplatin/pemetrexed. Patients and Methods Three hundred forty-five patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma were randomly assigned 2:1 to afatinib 40 mg per day or up to six cycles of cisplatin/pemetrexed. Lung cancer symptoms and health-related QoL were assessed every 21 days until progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Lung Cancer-13 questionnaires. Analyses of cough, dyspnea, and pain were preplanned, including percentage of patients who improved on therapy, time to deterioration of symptoms, and change in symptoms over time. Results Questionnaire compliance was high. Compared with chemotherapy, afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; 95% CI, 0.41 to 0.87; P = .007) and dyspnea (HR, 0.68; 95% CI, 0.50 to 0.93; P = .015), but not pain (HR, 0.83; 95% CI, 0.62 to 1.10; P = .19). More patients on afatinib (64%) versus chemotherapy (50%) experienced improvements in dyspnea scores (P lt; .010). Differences in mean scores over time significantly favored afatinib over chemotherapy for cough (P lt; .001) and dyspnea (P = .001). Afatinib showed significantly better mean scores over time in global health status/QoL (P = .015) and physical (P = .001), role (P = .004), and cognitive (P lt; .007) functioning compared with chemotherapy. Fatigue and nausea were worse with chemotherapy, whereas diarrhea, dysphagia, and sore mouth were worse with afatinib (all P = .01). Conclusion In patients with lung adenocarcinoma with EGFR mutations, first-line afatinib was associated with better control of cough and dyspnea compared with chemotherapy, although diarrhea, dysphagia, and sore mouth were worse. Global health status/QoL was also improved over time with afatinib compared with chemotherapy.

Investigating relationships between relationship quality, customer loyalty and cooperation : an empirical study of convenience stores' franchise chain systems

Franchising has become a way to minimise the risks of small business management. There has been little research into the factors that promote franchise relationship success. This study attempts to empirically examine the important elements (relationship quality, customer loyalty and cooperation), which might promote a successful long-term franchising relationship between franchisors and franchisees within the context of convenience stores in Taiwan. A model of these relationships was developed and tested. A total of 500 surveys were mailed to a random sample of convenience stores’ franchisee owners among the four main franchisors in Taiwan. The results show that relationship quality positively influences the cooperation between franchisors and franchisees and is positively correlated with franchisee loyalty. Additionally, the cooperative behaviour between franchisees and franchisors is significantly associated with franchisees’ loyalty.

Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone

The development of effective therapeutic strategies against prostate cancer bone metastases has been impeded by the lack of adequate animal models that are able to recapitulate the biology of the disease in humans. Bioengineered approaches allow researchers to create sophisticated experimentally and physiologically relevant in vivo models to study interactions between cancer cells and their microenvironment under reproducible conditions. The aim of this study was to engineer a morphologically and functionally intact humanized organ bone which can serve as a homing site for human prostate cancer cells. Transplantation of biodegradable tubular composite scaffolds seeded with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone construct including a large number of human mesenchymal cells which were shown to be metabolically active and capable of producing extracellular matrix components. Micro-CT analysis demonstrated that the newly formed ossicle recapitulated the morphological features of a physiological organ bone with a trabecular network surrounded by a cortex-like outer structure. This microenvironment was supportive of the lodgement and maintenance of murine haematopoietic cell clusters, thus mimicking a functional organ bone. Bioluminescence imaging demonstrated that luciferase-transduced human PC3 cells reproducibly homed to the humanized tissue engineered bone constructs, proliferated, and developed macro-metastases. This model allows the analysis of interactions between human prostate cancer cells and a functional humanized bone organ within an immuno-incompetent murine host. The system can serve as a reproducible platform to study effects of therapeutics against prostate cancer bone metastases within a humanized microenvironment.

A deconvolution method for deriving the transit time spectrum for ultrasound propagation through cancellous bone replica models

The acceptance of broadband ultrasound attenuation for the assessment of osteoporosis suffers from a limited understanding of ultrasound wave propagation through cancellous bone. It has recently been proposed that the ultrasound wave propagation can be described by a concept of parallel sonic rays. This concept approximates the detected transmission signal to be the superposition of all sonic rays that travel directly from transmitting to receiving transducer. The transit time of each ray is defined by the proportion of bone and marrow propagated. An ultrasound transit time spectrum describes the proportion of sonic rays having a particular transit time, effectively describing lateral inhomogeneity of transit times over the surface of the receiving ultrasound transducer. The aim of this study was to provide a proof of concept that a transit time spectrum may be derived from digital deconvolution of input and output ultrasound signals. We have applied the active-set method deconvolution algorithm to determine the ultrasound transit time spectra in the three orthogonal directions of four cancellous bone replica samples and have compared experimental data with the prediction from the computer simulation. The agreement between experimental and predicted ultrasound transit time spectrum analyses derived from Bland–Altman analysis ranged from 92% to 99%, thereby supporting the concept of parallel sonic rays for ultrasound propagation in cancellous bone. In addition to further validation of the parallel sonic ray concept, this technique offers the opportunity to consider quantitative characterisation of the material and structural properties of cancellous bone, not previously available utilising ultrasound.

Quality of life of women with lower limb swelling or lymphedema 3-5 years following endometrial cancer

Objective To quantitatively assess and compare the quality of life (QoL) of women with a self-reported diagnosis of lower limb lymphedema (LLL), to women with lower limb swelling (LLS), and to women without LLL or LLS following treatment for endometrial cancer. Methods 1399 participants in the Australian National Endometrial Cancer Study were sent a follow-up questionnaire 3–5 years after diagnosis. Women were asked if they had experienced swelling in the lower limbs and, if so, whether they had received a diagnosis of lymphedema by a health professional. The 639 women who responded were categorised as: Women with LLL (n = 68), women with LLS (n = 177) and women without LLL or LLS (n = 394). Multivariable-adjusted generalized linear models were used to compare women’s physical and mental QoL by LLL status. Results On average, women were 65 years of age and 4 years after diagnosis. Women with LLL had clinically lower physical QoL (M= 41.8, SE= 1.4) than women without LLL or LLS (M= 45.1, SE= 0.8, p = .07), however, their mental QoL was within the normative range (M= 49.6; SE= 1.1 p = 1.0). Women with LLS had significantly lower physical (M= 41.0, SE= 1.0, p = .003) and mental QoL (M= 46.8; SE= 0.8, p < .0001) than women without LLL or LLS (Mental QoL: M= 50.6, SE= 0.8). Conclusion Although LLL was associated with reductions in physical QoL, LLS was related to reductions in both physical and mental QoL 3-5 years after cancer treatment. Early referral to evidence-based lymphedema programs may prevent long-term impairments to women’s QoL.

The effect of a supervised exercise training programme on sleep quality in recently discharged heart failure patients

Background Sleep disturbances, including insomnia and sleep-disordered breathing, are a common complaint in people with heart failure and impair well-being. Exercise training (ET) improves quality of life in stable heart failure patients. ET also improves sleep quality in healthy older patients, but there are no previous intervention studies in heart failure patients. Aim The aim of this study was to examine the impact of ET on sleep quality in patients recently discharged from hospital with heart failure. Methods This was a sub-study of a multisite randomised controlled trial. Participants with a heart failure hospitalisation were randomised within six weeks of discharge to a 12-week disease management programme including exercise advice (n=52) or to the same programme with twice weekly structured ET (n=54). ET consisted of two one-hour supervised aerobic and resistance training sessions, prescribed and advanced by an exercise specialist. The primary outcome was change in Pittsburgh Sleep Quality Index (PSQI) between randomisation and week 12. Results At randomisation, 45% of participants reported poor sleep (PSQI≥5). PSQI global score improved significantly more in the ET group than the control group (–1.5±3.7 vs 0.4±3.8, p=0.03). Improved sleep quality correlated with improved exercise capacity and reduced depressive symptoms, but not with changes in body mass index or resting heart rate. Conclusion Twelve weeks of twice-weekly supervised ET improved sleep quality in patients recently discharged from hospital with heart failure.

Valuing those close to us : A comparison of German and Australian quality newspapers’ reporting of death in foreign news

A number of studies into the coverage of death have provided some evidence of journalists giving preference to events from certain regions and to certain types of death. This comprehensive evaluation of how two German and two Australian newspapers cover death specifically in foreign news finds clear evidence that journalists primarily look for events in countries which are culturally proximate to their own. The cultural proximity thesis here includes links such as cultural, political, economic or linguistic connections with a country. Some important national differences in how journalists at the Frankfurter Allgemeine Zeitung, Süddeutsche Zeitung, The Australian and The Sydney Morning Herald report on death were also identified. These could be traced to some important cultural differences between the two countries, underlining the need for more research which locates culture at the core of news analysis.

Voltage quality improvement in distribution networks containing DERs using UPQC

Single phase distributed energy resources (DERs) can cause voltage rise along distribution feeder and power imbalance among the phases. Usually transformer tap setting are used to mitigate voltage drop along feeders. However this can aggravate the voltage rise problem when DERs are connected. Moreover if the power generation in a phase is more than its load demand, the excess power in that phase will be fed back to the transmission network. In this paper, a unified power quality compensator (UPQC) has been utilized to alleviate the voltage quality excess power circulation problems. Through analysis and simulation results, the mode of operation of UPQC is highlighted. The proposals are validated through extensive digital computer simulation studies using PSCAD and MATLAB.

Mesenchymal stem cell therapies for bone and tendon conditions

Bone, tendon, and cartilage are highly specialized musculoskeletal connective tissues that are subject to injury and degeneration. These tissues have relatively poor healing capabilities, and coupled with their variable response to established medical treatments, produce significant morbidity. Mesenchymal stem cells (MSCs) are capable of regenerating skeletal tissues and therefore offer great promise in the treatment of connective tissue pathologies. Adult MSCs are multipotent cells that possess the properties of proliferation and differentiation into all connective tissues. Furthermore, they can be gene modified to secrete growth factors and utilized in connective tissue engineering. Potential MSC-based therapies for bone and tendon conditions are reviewed in this chapter.

methoxy-poly(ethylene glycol) modified poly(L-lactide) enhanced cell affinity of human bone marrow stromal cells by the upregulation of 1-cadherin and delta-2-catenin

Poly(l-lactide) (PLLA), a versatile biodegradable polymer, is one of the most commonly-used materials for tissue engineering applications. To improve cell affinity for PLLA, poly(ethylene glycol) (PEG) was used to develop diblock copolymers. Human bone marrow stromal cells (hBMSCs) were cultured on MPEG-b-PLLA copolymer films to determine the effects of modification on the attachment and proliferation of hBMSC. The mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analyzed using RT-qPCR to understand the underlying mechanisms. It was found that MPEG-b-PLLA copolymer films significantly improved cell adhesion, extension, and proliferation.This was found to be related to the significant upregulation of two adhesion genes, CDH1 and CTNND2, which encode 1-cadherin and delta-2-catenin, respectively, two key components for the cadherin-catenin complex. In summary, MPEG-b-PLLA copolymer surfaces improved initial cell adhesion by stimulation of adhesion molecule gene expression.

Experimental evaluation of an autonomous surface vehicle for water quality and greenhouse gas emission monitoring

This paper describes the experimental evaluation of a novel Autonomous Surface Vehicle capable of navigating complex inland water reservoirs and measuring a range of water quality properties and greenhouse gas emissions. The 16 ft long solar powered catamaran is capable of collecting water column profiles whilst in motion. It is also directly integrated with a reservoir scale floating sensor network to allow remote mission uploads, data download and adaptive sampling strategies. This paper describes the onboard vehicle navigation and control algorithms as well as obstacle avoidance strategies. Experimental results are shown demonstrating its ability to maintain track and avoid obstacles on a variety of large-scale missions and under differing weather conditions, as well as its ability to continuously collect various water quality parameters complimenting traditional manual monitoring campaigns.

An autonomous surface vehicle for water quality monitoring

This paper describes a novel Autonomous Surface Vehicle capable of navigating throughout complex inland water storages and measuring a range of water quality properties and greenhouse gas emissions. The 16 ft long solar powered catamaran can collect this information throughout the water column whilst the vehicle is moving. A unique feature of this ASV is its integration into a storage scale floating sensor network to allow remote mission uploads, data download and adaptive sampling strategies. This paper provides an overview of the vehicle design and operation including control, laser-based obstacle avoidance, and vision-based inspection capabilities. Experimental results are shown illustrating its ability to continuously collect key water quality parameters and compliment intensive manual monitoring campaigns.