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Early and Locally Advanced Breast Cancer: Diagnosis and Treatment [Internet]

Breast cancer is the most common cancer in women and its management often presents patients and their healthcare professionals with difficult decisions about the most appropriate treatment. For all those affected by breast cancer (including family and carers) it is important to recognise the impact of this diagnosis, the complexity of treatment options and the wide ranging needs and support required throughout this period of care and beyond. We hope that this document will provide helpful and appropriate guidance to both healthcare professionals and patients on the diagnosis and subsequent management of early and locally advanced breast cancer.

NICE Clinical Guidelines - National Collaborating Centre for Cancer (UK).

Version: February 2009
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Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis

CONTEXT: Osteoporosis and osteopenia are associated with increased fracture incidence.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

The evidence for efficacy of osteoporosis treatment in men with primary osteoporosis: a systematic review and meta-analysis of antiresorptive and anabolic treatment in men

Purpose. Fragility fractures in men constitute a major worldwide public health problem with a life-time risk of 13%. It cannot be directly inferred that antiosteoporotic drugs effective in women have the same effect in men. Our aim was to appraise the existing evidence for efficacy of osteoporosis treatment in men. Methods. This study was a systematic review of the published literature on the clinical efficacy of medical osteoporosis therapy in the reduction of fracture risk in men (age > 50 years). Studies included were randomised, placebo-controlled trials of men. Results. Five BMD studies of antiresorptive treatment were included. All studies showed an increase in BMD, but there was only a nonsignificant trend in the reduction of clinical fractures. Three BMD studies of anabolic treatment with teriparatide were also included. These showed a significant mean increase in spine BMD and for vertebral fractures a non-significant trend towards a reduction was seen. Conclusion. The evidence of medical osteoporosis treatment in men is scant and inconclusive due to the lack of prospective RCT studies with fracture prevention as primary end point. So far, all evidence is based on BMD increases in small RCT studies showing BMD increases comparable to those reported in postmenopausal women.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Comparative effectiveness of pharmacologic treatments to prevent fractures: an updated systematic review

BACKGROUND: Osteoporosis is a major contributor to the propensity to fracture among older adults, and various pharmaceuticals are available to treat it.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Single and combined use of human parathyroid hormone (PTH) (1-34) on areal bone mineral density (aBMD) in postmenopausal women with osteoporosis: evidence based on 9 RCTs

BACKGROUND: Human parathyroid hormone (PTH) (1-34) or teriparatide (TPTD) is an anabolic agent for osteoporosis. This recombinant protein stimulates positive bone formation balance and bone remodeling. However, when concomitantly used with antiresorptive (AR) agents, previous studies reported conflicting results in their potential additive and synergistic effects on bone metabolism and bone mineral density (BMD). This study aimed to integrate previous evidence to assess the effect of TPTD monotherapy and the additive effect of TPTD on AR agents in postmenopausal women with osteoporosis.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Effects of increasing age, dosage, and duration of PTH treatment on BMD increase: a meta-analysis

We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present), or Embase (1974 to present). The search date was November 16, 2010. All studies comparing PTH treatment to either placebo or antiresorptive drugs--for example, bisphosphonates or hormone replacement therapy--were included. A total of 214 studies were identified in the initial search, and 15 of these trials were included. By metaregression analysis, we found that the increase in spine BMD (Z-score) after PTH treatment was blunted by increasing age (R(2) = 0.27; 2p = 0.01, slope -0.023 Z-scores per year, 11 studies). By increasing PTH dosage (μg/d), spine BMD increased significantly (2p = 0.002) with a slope of +0.011 Z-scores/μg/d of teriparatide. Furthermore, the duration of treatment was positively correlated to spine BMD (P < 0.001) with a slope of +0.043 Z-score for each extra month of treatment. We evaluated the BMD effect in hips and found no age dependency (R(2) = 0.04; P = 0.66; 8 studies). However, for the spine, we found a significant relation to daily dosage (P = 0.011), Z-score coefficient 0.0051 ± 0.0020 (2p < 0.01). The treatment duration also correlated positively by a Z-score coefficient of 0.0170 ± 0.0053, 2p < 0.01 per extra month of treatment. PTH treatment alone seems to be able to improve BMD significantly. However, the BMD increase was significantly lower with increasing age in the spine. No age dependency was observed in the hips. In general the effect of treatment was improved with increasing dosage and duration of treatment from 6 to 36 months.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups

BACKGROUND: There is currently no standard practice for the monitoring of patients receiving treatment for osteoporosis. Repeated dual-energy X-ray absorptiometry (DXA) is commonly used for monitoring treatment response, but it has its limitations. Bone turnover markers have advantages over DXA as they are non-invasive, relatively cheap and can detect changes in bone turnover rates earlier. However, they do have disadvantages, particularly high within- and between-patient variability. The ability of bone turnover markers to identify treatment non-responders and predict future fracture risk has yet to be established.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

The relative efficacy of nine osteoporosis medications for reducing the rate of fractures in post-menopausal women

The authors concluded that indirect treatment comparisons indicated teriparatide, zoledronic acid and denosumab had the highest probabilities of being most efficacious for non-vertebral and vertebral fractures. In the absence of direct comparisons, the evidence presented may be the best available. However, the authors' conclusions should be considered tentative given limitations of the evidence and synthesis.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis

The authors concluded that there were differences in fracture risk reduction profiles between pharmacologic therapies for postmenopausal osteoporosis and the findings may assist therapy choice. The authors’ conclusions are generally suitably cautious but it remains unclear which of the treatments for osteoporosis most effective.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Effect of osteoporosis treatment on mortality: a meta-analysis

This review concluded that effective treatments for fracture prevention in osteoporosis reduced mortality in older, frailer individuals with osteoporosis who were at high risk of fracture. Weaknesses in the review methods and reporting and interpretation of results mean that these conclusions should be viewed cautiously.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

Prevention of vertebral fractures in osteoporosis: mixed treatment comparison of bisphosphonate therapies

This review showed that zoledronic acid appeared to reduce risk of vertebral fracture in comparison to ibandronate, alendronate and risedronate in postmenopausal women with osteoporosis. However, the absence of a validity assessment, risk of publication bias and reliance on indirect mixed treatment comparisons suggested that the authors’ conclusions should be interpreted with caution.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2009

The efficacy of bisphosphonates in the prevention of vertebral, hip, and nonvertebral-nonhip fractures in osteoporosis: a network meta-analysis

The review concluded that, in women with osteoporosis, zoledronic acid had the highest probability of preventing vertebral fractures and was comparable with alendronate in preventing hip fractures; risedronate was superior in preventing non-vertebral and non-hip fractures. The potential for biases within the review and the uncertain quality of included trials mean that caution is warranted when interpreting the authors’ conclusions.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

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