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The global burden of type 2 diabetes is growing. Traditional therapies are suboptimal and there is a clear unmet need for treatments that offer effective glucose control while addressing the comorbid factors associated with diabetes, such as obesity and risk of cardiovascular disease, without the fear of hypoglycaemia. Glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors offer a novel way of reducing hyperglycaemia by targeting the incretin system. This review provides an overview of the development of incretin‐based therapies and explains their differing modes of action compared with traditional interventions. A comparison of the clinical profiles of current glucagon‐like peptide‐1 receptor agonists [liraglutide and exenatide (twice‐daily and once‐weekly)] and dipeptidyl peptidase‐4 inhibitors (sitagliptin, saxagliptin, vildagliptin and linagliptin) is performed alongside a discussion of the placement of incretin‐based therapies in treatment guidelines. Further improvements in this class are expected, and we will examine some of the novel glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors currently under development.  相似文献   
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Aim: Effective type 2 diabetes management requires a multifactorial approach extending beyond glycaemic control. Clinical practice guidelines suggest targets for HbA1c, blood pressure and lipids, and emphasize weight reduction and avoiding hypoglycaemia. The phase 3 clinical trial programme for liraglutide, a human glucagon‐like peptide 1 analogue, showed significant improvements in HbA1c and weight with a low risk of hypoglycaemia compared to other diabetes therapies. In this context, we performed a meta‐analysis of data from these trials evaluating the proportion of patients achieving a clinically relevant composite measure of diabetes control consisting of an HbA1c <7% without weight gain or hypoglycaemia. Methods: A prespecified meta‐analysis was performed on 26‐week patient‐level data from seven trials (N = 4625) evaluating liraglutide with commonly used therapies for type 2 diabetes: glimepiride, rosiglitazone, glargine, exenatide, sitagliptin or placebo, adjusting for baseline HbA1c and weight, for a composite outcome of HbA1c <7.0%, no weight gain and no hypoglycaemic events. Results: At 26 weeks, 40% of the liraglutide 1.8 mg group, 32% of the liraglutide 1.2 mg group and 6–25% of comparators (6% rosiglitazone, 8% glimepiride, 15% glargine, 25% exenatide, 11% sitagliptin, 8% placebo) achieved this composite outcome. Odds ratios favoured liraglutide 1.8 mg by 2.0‐ to 10.5‐fold over comparators. Conclusions: As assessed by the composite outcome of HbA1c <7%, no hypoglycaemia and no weight gain, liraglutide was clearly superior to the other commonly used therapies. However, the long‐term clinical impact of this observation remains to be shown.  相似文献   
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Background

A sound understanding of the benefits of different treatment options and their health-related quality of life (HRQoL) impacts is required for optimal breast cancer care.

Methods

A cross-sectional cohort study was conducted to determine the prevalence and severity of persistent functional decrements and symptoms and identify demographic, clinical and treatment variables associated with poorer outcomes. Four hundred English-speaking women treated for ductal carcinoma-in-situ or stage I to III breast cancer between 1999 and 2009, at least 12 months after surgery and currently disease free, were randomly selected and invited to complete (1) the Breast Cancer Treatment Outcome Scale and (2) the EORTC core Quality of Life Questionnaire, version 3.

Results

The response rate was 85.60 %. Many participants reported moderate to severe decrements in a number of HRQoL domains, including functional well-being (15 %), cosmetic status (32 %) and overall quality of life (21 %). There were significant associations (p < .05) between younger age and poorer HRQoL but none between time since surgery and morbidity (p > .05). Different treatments were associated with different HRQoL impacts. Poorer functional status was predicted by axillary dissection (p = .011), and adjuvant radiotherapy was a significant predictor of breast-specific pain (p < .05).

Conclusions

Many breast cancer survivors report long-term morbidity that is unaffected by time since surgery. The significant associations between the extent of locoregional therapies and poorer HRQoL outcomes emphasize the importance of the safe tailoring of these treatments.  相似文献   
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OBJECTIVES: To assess the occurrence and prognostic factors for the ability to maintain paid work in patients with rheumatoid arthritis (RA). SETTING: Inception cohort of patients with RA recruited from rheumatology departments in nine NHS Hospital Trusts in England. PATIENTS: All consecutive patients with RA of less than two years' duration, before any second line (disease modifying) drug treatment, and followed up for five years. METHODS: Clinical, laboratory, and radiological assessments, and all treatments were recorded prospectively using a standardised format at presentation and yearly. OUTCOME MEASURES: Changes in, and loss of paid work by five years' follow up. RESULTS: 732 patients completed the five year follow up. 353/721 (49%) were gainfully employed at the onset of RA, 211 (60%) were still working at five years, 104 (29%) stopped because of the disease, and 31 (9%) retired for reasons other than RA. Work disability at five years was more likely in manual workers (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.4 to 3.8) and worse baseline Health Assessment Questionnaire (HAQ>1.5, OR 2.26, 95% CI 1.38 to 3.7). In combination with other baseline variables (erythrocyte sedimentation rate, sex, age of onset, and radiological erosions), employment outcome was predicted in 78% using multivariate analysis. CONCLUSIONS: Nearly half of the patients with RA were in paid employment at onset, work disability was an adverse outcome for a third of these patients by five years, and manual work and high baseline HAQ were important predictors for this. These details are likely to be useful to clinicians, health professionals, and patients in order to plan medical, orthopaedic, and remedial treatments in early RA. Future disease modifying treatments could be compared with this cohort of patients who were treated with conventional second line drugs.  相似文献   
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For both clinical and economic reasons, the increasing number of persons living with chronic conditions represents a public health issue of growing importance. Emphasizing patient responsibility, and acting in concert with the provider community, self-management represents a promising strategy for treating chronic conditions—moving beyond education to teaching individuals to actively identify challenges and solve problems associated with their illness. Self-management also shows potential as an effective paradigm across the prevention spectrum (primary, secondary, and tertiary) by establishing a pattern for health early in life and providing strategies for mitigating illness and managing it in later life. We suggest ways to advance research methods and practical applications of self-management as steps in its future development and implementation.Improvements in health care have resulted in greater numbers of people living with multiple chronic conditions for longer periods of time. With this change, chronic illness is now a major focus of health care.1 At the same time, increased attention has been concentrated on approaches to manage chronic symptoms to maintain patient independence and quality of life over longer periods of time. Approaches to managing chronic illness are shifting from the traditional provider–patient relationship to a paradigm in which individuals with chronic conditions play a key role in guiding their care, in partnership with health care providers.2,3Many prevalent chronic conditions, such as heart disease, diabetes, and arthritis, though unique in their own attributes and demands, share common challenges associated with their management. These include dealing with symptoms and disability; monitoring physical indicators; managing complex medication regimens; maintaining proper levels of nutrition, diet, and exercise; adjusting to the psychological and social demands, including difficult lifestyle adjustments; and engaging in effective interactions with health care providers.4,5The identification and elaboration of common patient-centric strategies to deal with these challenges is the focus of the field of self-management.6,7 Regardless of the chronic condition, the development of a generic set of skills has proven successful in allowing individuals to effectively manage their illness and improve health outcomes.8 A 2010 report by the Department of Health and Human Services included self-management as one of 4 goals in a strategic framework for improving the health status of individuals with multiple chronic conditions.9 More recently, the 2012 Institute of Medicine report “Living Well With Chronic Illness: A Call for Public Health Action” included self-management10 as one of several models of living well interventions, noting that self-management programs instill individual responsibility and offer tools for patients to use in caring for their chronic illness.10There is increasing recognition that chronic illness, including its prevention, treatment and management, represents a public health as well as a clinical issue.11,12 Indeed, the Institute of Medicine report noted that a population health perspective for developing strategies, interventions, and policies to combat chronic illness is critical.10 Community-based self-management intervention programs are one aspect of a population-based approach addressing the larger public health problem of chronic conditions in the United States and across the globe. There is an extensive body of literature related to self-management of chronic conditions, but our intent with this article is not to provide a comprehensive review, but rather to highlight the unique contribution of nurse scientists to the field.Nursing science has enhanced the care of individual patients and has tested interventions that can be scaled up for implementation at the population level. We present examples of nursing science that demonstrate effectiveness, promise sustainability and scalability, and set the foundation for implementing wide-reaching public health actions for managing chronic illness.12There is increased awareness of the need to promote conceptual clarity regarding self-management and its integration into clinical practice. Equally important is the requirement to develop more sophisticated models of self-management, tailored to various health conditions and situations. Fundamental to the development of such models and their practical application is the need to conduct research that informs self-management practice and contributes to health policy.The nursing community, comprising both researchers and clinicians, plays a crucial role in efforts to provide the evidence base for innovative self-management practices, and is ideally positioned to implement those advances in a practical manner. Over the course of its history, the National Institute of Nursing Research (NINR) at the National Institutes of Health (NIH) has promoted self-management science as one of its core areas of investigation, supporting research to improve and manage symptoms of acute and chronic illness.13 Recognizing that self-management represents a topic of ever-increasing importance, a goal of NINR is to advance the science of self-management and, ultimately, disseminate results widely for translation into clinical practice.Recently, a group of nurse scientist leaders assembled to discuss “The Science of Chronic Illness Self-Management” as the topic of the 2013 National Nursing Research Roundtable. The Roundtable is an annual meeting with the purpose of providing a regular forum of communication about the direction and conduct of nursing research. Discussions from this year’s meeting resulted in a set of recommended areas of focus and approaches to advance the field and practice of self-management (see the box on this page).

Recommended Areas of Focus and Approaches to Advancing Self-Management

Conceptual clarity
Standardize language by incorporating uniform, agreed-upon language into the National Library of Medicine’s medical subject headings.
Key areas of research
Expand comparative effectiveness studies of interventions to compare
 Outcomes
 Quality of care
 Cost
Identify the most valid measures of self-management.
Explore the use of statistical modeling to simulate intervention outcomes.
Identify and study relevant biological and genetic variables.
Identify mediating factors
 Related to sustaining self-management
 For tailoring to individuals
Identify and incorporate elements of program scalability, sustainability, cost-effectiveness, and reach.
Expand research to widen the application of self-management technology (Internet, social media).
Methodologies for future studies
Implement a collaborative, multidisciplinary methods approach.
Use statistical modeling: systems-based modeling—for connecting underlying complex elements of self-management.
Conduct pragmatic clinical trials and use common data elements across studies.
Dissemination and communication of research
Disseminate research results widely to include policy and clinical practice audiences.
Publish in high-impact clinical journals and seminal science publications.
Coordinate with professional organizations to disseminate results and sponsor public forums to broaden awareness of self-management.
Provide communication, outreach, and media training to encourage and enhance communication to lay audiences.
Translation into clinical practice
Enhance evidence to improve clinical care.
 Identify self-management interventions most likely to improve health outcomes.
 Emphasize evidence-based professional training curricula.
Incorporate self-management into primary care.
 Engage patients to share self-management experience.
 Serve as a resource for local self-management support information.
Tailor self-management to individual needs.
 Consider cultural norms and traditions.
 Engage patients as to their functional goals.
Transition health care system policies and practices to incentivize and promote self-management.
 Use self-management programs as a way to decrease or stabilize costs to payer.
 Reimburse providers for prescribing proven self-management techniques.
 Use interprofessional approach to developing self-management intervention programs.
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48.
It is assumed that sheep and goats consumed the same bovine spongiform encephalopathy (BSE)-contaminated meat and bone meal that was fed to cattle and precipitated the BSE epidemic in the United Kingdom that peaked more than 20 years ago. Despite intensive surveillance for cases of BSE within the small ruminant populations of the United Kingdom and European Union, no instances of BSE have been detected in sheep, and in only two instances has BSE been discovered in goats. If BSE is present within the small ruminant populations, it may be at subclinical levels, may manifest as scrapie, or may be masked by coinfection with scrapie. To determine whether BSE is potentially circulating at low levels within the European small ruminant populations, highly sensitive assays that can specifically detect BSE, even within the presence of scrapie prion protein, are required. Here, we present a novel assay based on the specific amplification of BSE PrPSc using the serial protein misfolding cyclic amplification assay (sPMCA), which specifically amplified small amounts of ovine and caprine BSE agent which had been mixed into a range of scrapie-positive brain homogenates. We detected the BSE prion protein within a large excess of classical, atypical, and CH1641 scrapie isolates. In a blind trial, this sPMCA-based assay specifically amplified BSE PrPSc within brain mixes with 100% specificity and 97% sensitivity when BSE agent was diluted into scrapie-infected brain homogenates at 1% (vol/vol).  相似文献   
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