New findings with old drugs for osteoporosis

Background : Postmenopausal osteoporosis is common and is associated with stooped posture, loss of height, back pain and fractures. Objectives/methods : This evaluation is of clinical outcome trials with tibolone (Long-Term Intervention of Fractures with Tibolone) and strontium ranelate (Spinal Osteoporosis Therapeutic Intervention) in postmenopausal osteoporosis. Results : Although the Long-Term Intervention of Fractures with Tibolone trial established that tibolone decreased the incidence of vertebral and non-vertebral fractures in postmenopausal osteoporosis, it also showed that tibolone caused a small increase in the incidence of stoke. The Spinal Osteoporosis Therapeutic Intervention trial established that strontium ranelate decreased the incidence of vertebral fractures, but had little effect on the incidence of non-vertebral fractures. Conclusions : As some of the bisphosphonates (alendronate, risedronate, zoledronic acid) have been shown to prevent hip fractures without increasing the incidence of stroke, they should be preferred to tibolone and strontium in the treatment of postmenopausal osteoporosis.

Clinical efficacy and safety of zoledronic acid in osteoporosis and Paget's disease

Osteoporosis and Paget’s bone disease are the most common diseases of the bone. In addition to glucocorticoid treatment, there are many other secondary causes of osteoporosis. Bisphosphonates are used to treat these bone conditions. Zoledronic acid is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least 1 year following a single intravenous administration. The efficacy and safety of zoledronic acid in the treatment of osteoporosis and Paget’s bone disease are reviewed. This article also covers the studies of the effects of zoledronic acid in the bone loss associated with the secondary osteoporosis.

Good clinical endpoints with denosumab in osteoporosis and cancer

Background: Bone loss associated with low oestrogen levels in postmenopausal women, and with androgen deprivation therapy in men with hormone-sensitive prostate cancer, result in an increased incidence of fractures. Denosumab has been shown to increase bone mineral density in these two conditions. Objectives/methods: The objective of this evaluation is to review the clinical trials that have studied clinical endpoints in these conditions. Results: FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) was an International Phase III clinical trial that measured the clinical endpoints with denosumab in postmenopausal women with osteoporosis. At 36 months, new vertebral fractures had occurred in 7.2% of subjects in the placebo group and this was lowered to 2.3% of subjects treated with denosumab. HALT (Denosumab Hormone Ablation Bone Loss Trial) studied the clinical endpoints in men with non-metastatic prostate cancer receiving androgen-deprivation therapy. The incidence of vertebral fractures was significantly lower in the denosumab group (1.5%) than in the placebo group (3.9%). The incidence of adverse effects with denosumab in both clinical trials was low. Conclusions: Denosumab reduces the incidence of fractures in postmenopausal women with osteoporosis and in men with non-metastatic prostate cancer receiving androgen-deprivation therapy. Denosumab is well tolerated.

Cardiac state diagnosis using higher order spectra of heart rate variability

Heart rate variability (HRV) refers to the regulation of the sinoatrial node, the natural pacemaker of the heart, by the sympathetic and parasympathetic branches of the autonomic nervous system. Heart rate variability analysis is an important tool to observe the heart's ability to respond to normal regulatory impulses that affect its rhythm. A computer-based intelligent system for analysis of cardiac states is very useful in diagnostics and disease management. Like many bio-signals, HRV signals are nonlinear in nature. Higher order spectral analysis (HOS) is known to be a good tool for the analysis of nonlinear systems and provides good noise immunity. In this work, we studied the HOS of the HRV signals of normal heartbeat and seven classes of arrhythmia. We present some general characteristics for each of these classes of HRV signals in the bispectrum and bicoherence plots. We also extracted features from the HOS and performed an analysis of variance (ANOVA) test. The results are very promising for cardiac arrhythmia classification with a number of features yielding a p-value < 0.02 in the ANOVA test.

Best basis-based intelligent machine fault diagnosis

The wavelet packet transform decomposes a signal into a set of bases for time–frequency analysis. This decomposition creates an opportunity for implementing distributed data mining where features are extracted from different wavelet packet bases and served as feature vectors for applications. This paper presents a novel approach for integrated machine fault diagnosis based on localised wavelet packet bases of vibration signals. The best basis is firstly determined according to its classification capability. Data mining is then applied to extract features and local decisions are drawn using Bayesian inference. A final conclusion is reached using a weighted average method in data fusion. A case study on rolling element bearing diagnosis shows that this approach can greatly improve the accuracy ofdiagno sis.

Future developments in chest pain diagnosis and management

Much of the focus of research on patients with chest pain is directed at technological advances in the diagnosis and management of acute coronary syndrome (ACS), pulmonary embolism (PE), and acute aortic dissection (AAD), despite there being no significant difference at 4 years as regards mortality, ongoing chest pain, and quality of life between patients presenting to the emergency department with noncardiac chest pain and those with cardiac chest pain. This article examines future developments in the diagnosis and management of patients with suspected ACS, PE, AAD, gastrointestinal disease, and musculoskeletal chest pain.

25th anniversary of BUA for the assessment of osteoporosis : time for a new paradigm?

The measurement of broadband ultrasonic attenuation (BUA) in cancellous bone at the calcaneus for the assessment of osteoporosis was first described within this journal 25 years ago. It was recognized in 2006 by Universities UK as being one of the ‘100 discoveries and developments in UK Universities that have changed the world’ over the past 50 years. In 2008, the UK's Department of Health also recognized BUA assessment of osteoporosis in a publication highlighting 11 projects that have contributed to ‘60 years of NHS research benefiting patients’. The BUA technique has been extensively clinically validated and is utilized worldwide, with at least seven commercial systems currently providing calcaneal BUA measurement. However, there is still no fundamental understanding of the dependence of BUA upon the material and structural properties of cancellous bone. This review aims to provide an ‘engineering in medicine’ perspective and proposes a new paradigm based upon phase cancellation due to variation in propagation transit time across the receive transducer face to explain the non-linear relationship between BUA and bone volume fraction in cancellous bone.

Does research into sensitive areas do harm? Experiences of research participation after a child’s diagnosis with Ewing’s Sarcoma

Objective: To investigate family members’ experiences of involvement in a previous study (conducted August 1995 to June 1997) following their child’s diagnosis with Ewing’s sarcoma. Design: Retrospective survey, conducted between 1 November and 30 November 1997, using a postal questionnaire. Participants: Eighty-one of 97 families who had previously completed an in-depth interview as part of a national case–control study of Ewing’s sarcoma. Main outcome measures: Participants’ views on how participation in the previous study had affected them and what motivated them to participate. Results: Most study participants indicated that taking part in the previous study had been a positive experience. Most (n = 79 [97.5%]) believed their involvement would benefit others and were glad to have participated, despite expecting and finding some parts of the interview to be painful. Parents whose child was still alive at the time of the interview recalled participation as more painful than those whose child had died before the interview. Parents who had completed the interview less than a year before our study recalled it as being more painful than those who had completed it more than a year before. Conclusions: That people suffering bereavement are generally eager to participate in research and may indeed find it a positive experience is useful information for members of ethics review boards and other “gatekeepers”, who frequently need to determine whether studies into sensitive areas should be approved. Such information may also help members of the community to make an informed decision regarding participation in such research.

Does quality of life among breast cancer survivors one year after diagnosis differ depending on urban and non-urban residence? A comparative study

Background: This study examined the quality of life (QOL), measured by the Functional Assessment of Cancer Therapy (FACT) questionnaire, among urban (n=277) and non-urban (n=323) breast cancer survivors and women from the general population (n=1140) in Queensland, Australia. ---------- Methods: Population-based samples of breast cancer survivors aged <75 years who were 12 months post-diagnosis and similarly-aged women from the general population were recruited between 2002 and 2007. ---------- Results: Age-adjusted QOL among urban and non-urban breast cancer survivors was similar, although QOL related to breast cancer concerns was the weakest domain and was lower among non-urban survivors than their urban counterparts (36.8 versus 40.4, P<0.01). Irrespective of residence, breast cancer survivors, on average, reported comparable scores on most QOL scales as their general population peers, although physical well-being was significantly lower among non-urban survivors (versus the general population, P<0.01). Overall, around 20%-33% of survivors experienced lower QOL than peers without the disease. The odds of reporting QOL below normative levels were increased more than two-fold for those who experienced complications following surgery, reported upper-body problems, had higher perceived stress levels and/or a poor perception of handling stress (P<0.01 for all). ---------- Conclusions: Results can be used to identify subgroups of women at risk of low QOL and to inform components of tailored recovery interventions to optimize QOL for these women following cancer treatment.