The bone remodelling cycle.

The bone remodelling cycle replaces old and damaged bone and is a highly regulated, lifelong process essential for preserving bone integrity and maintaining mineral homeostasis. During the bone remodelling cycle, osteoclastic resorption is tightly coupled to osteoblastic bone formation. The remodelling cycle occurs within the basic multicellular unit and comprises five co-ordinated steps; activation, resorption, reversal, formation and termination. These steps occur simultaneously but asynchronously at multiple different locations within the skeleton. Study of rare human bone disease and animal models have helped to elucidate the cellular and molecular mechanisms that regulate the bone remodelling cycle. The key signalling pathways controlling osteoclastic bone resorption and osteoblastic bone formation are receptor activator of nuclear factor-κB (RANK)/RANK ligand/osteoprotegerin and canonical Wnt signalling. Cytokines, growth factors and prostaglandins act as paracrine regulators of the cycle, whereas endocrine regulators include parathyroid hormone, vitamin D, calcitonin, growth hormone, glucocorticoids, sex hormones, and thyroid hormone. Disruption of the bone remodelling cycle and any resulting imbalance between bone resorption and formation leads to metabolic bone disease, most commonly osteoporosis. The advances in understanding the cellular and molecular mechanisms underlying bone remodelling have also provided targets for pharmacological interventions which include antiresorptive and anabolic therapies. This review will describe the remodelling process and its regulation, discuss osteoporosis and summarize the commonest pharmacological interventions used in its management.

The Nottingham Prognostic Index: five- and ten-year data for all-cause survival within a screened population.

INTRODUCTION: The Nottingham Prognostic Index (NPI) is an established prognostication tool in the management of breast cancers (BCs). Latest ten-year survival data have demonstrated an improved outlook for each NPI category and the latest UK five- and ten-year survival from BC has been reported to be 85% and 77%, respectively. We compared survival of each NPI category for BCs diagnosed within the national breast screening service in Wales (Breast Test Wales (BTW)) to the latest data, and reviewed its validity in unselected cases within a screened population. METHODS: All women screened between 1998 and 2001 within BTW were included. The NPI score for each cancer was calculated using the size, nodal status, and grade of the primary tumour. Survival data (all-cause) were calculated after ten years of follow-up. RESULTS: In the three-year screening period, 199,082 women were screened. A total of 1,712 cancers were diagnosed, and 1,546 had data available for calculating the NPI. Overall five-year and ten-year survival was 94% and 82%, respectively. CONCLUSIONS: Overall five-year and ten-year survival (all-cause) has improved even when compared with UK data for BC-specific survival. We found that the NPI remains valid for BC treatment, and that our data provide a reference for updating the all-cause survival of women diagnosed with BCs within a screened population.

The incidence and 10-year survival of interval breast cancers in Wales.

AIM: To evaluate the number of interval cancers (IC) within one screening cycle and the overall 10-year survival of IC, including its four main classifications, and compare that to screen-detected cancers (SDC). MATERIALS AND METHODS: Within Breast Test Wales (BTW), all SDC between the years 1998 and 2001 were included. IC that occurred between 1998 and 2003 that had undergone screening between the years 1998 and 2001 were also included. These IC were classified into true interval (TI), false negative (FN), occult cancer (OCC), and unclassified cancer (UCC). BTW received notification of all deaths of women that had undergone screening; thus, the 10-year all-cause survival rate was calculated from the date of diagnosis and death. RESULTS: During the study period, 199,082 women attended screening. Of these, 1020 (0.51%) women had SDC and 692 (0.38%) women developed IC. Of the 692 IC, 391 (57.8%) were TI, 120 (17.7%) were FN, 68 (10%) were OCC, and 98 (14.5%) were UCC; 15 (2.2%) were not classified. After a 10-year follow-up period, the 10-year survival rate (all-cause) for SDC was 81.6%, overall for all of IC was 72.4% (OR = 1.67, p < 0.001), TI was 77.5% (OR = 1.00, p = 0.99), FN was 55% (OR = 2.36, p < 0.001), OCC was 54.4% (OR = 3.17, p < 0.001), and UCC was 87.8% (OR = 0.61, p = 0.19). CONCLUSIONS: The overall 10-year survival of IC was significantly different to SDC. However, within this, the prognosis of TI was similar to SDC, whereas FN and OCC had significantly worse long-term survival. Further research is required to identify the underlying cause of poor survival of FN and OCC.

Streptococcus equi subspecies zooepidemicus meningitis--a case report and review of the literature.

A case is described of a 79-year-old man, trampled by his horses, who subsequently developed a wound infection and, later, meningitis. Streptococcus equi subsp. zooepidemicus was isolated as the causative organism. S. equi subsp. zooepidemicus, which carries the Lancefield Group C antigen, is an uncommon human pathogen but is commonly isolated from bacterial infections in animals, particularly horses. It is most commonly acquired by humans following animal contact. A review of the literature identified 20 previously described cases of S. equi subsp. zooepidemicus meningitis. Crude mortality following infection was 24%. All of the patients who died were over 70 years of age and the ingestion of unpasteurised dairy products was associated with all but one of the fatal cases. Hearing loss was a frequent complication, occurring in 19% of cases. Only 38% of patients made a complete recovery. Treatment regimes commonly included benzylpenicillin or a third-generation cephalosporin, with a mean treatment duration in survivors of 23 days.

Current practice and knowledge of nurses regarding patient temperature measurement.

BACKGROUND: The measurement of patient temperature by nursing staff is a common activity. In recent years this area of practice has been largely under-investigated despite the introduction of new technologies into clinical practice, such as infrared tympanic thermometry (IRTT). STUDY AIM: To investigate current practice in clinical temperature measurement in general, and the use of IRTT in particular by nursing staff. SAMPLE AND METHODS: 139 nursing staff from a general hospital in the UK were surveyed via a self-administered questionnaire. MAIN FINDINGS AND CONCLUSIONS: The group most involved in temperature measurement was characterized as nursing auxiliary grades with the fewest years of experience. IRTT was the most frequently-used method for measuring patient temperatures, with high perceived accuracy, reliability, ease of use and acceptability to patients. A poor level of understanding and training in the use of IRTT was revealed across all clinical grades. Recommendations for future investigations are made.

Extremely rapid recovery of human cone circulating current at the extinction of bleaching exposures.

We used a conductive fibre electrode placed in the lower conjunctival sac to record the a-wave of the human photopic electroretinogram elicited by bright white flashes, delivered during, or at different times after, exposure of the eye to bright white illumination that bleached a large fraction (approximately 90%) of the cone photopigment. During steady-state exposures of this intensity, the amplitude of the bright-flash response declined to approximately 50% of its dark-adapted level. After the intense background was turned off, the amplitude of the bright-flash response recovered substantially, for flashes presented within 20 ms of background extinction, and fully, for flashes presented 100 ms after extinction. In addition, a prominent 'background-off a-wave' was observed, beginning within 5-10 ms of background extinction. We interpret these results to show, firstly, that human cones are able to preserve around half of their circulating current during steady-state illumination that bleaches 90% of their pigment and, secondly, that following extinction of such illumination, the cone circulating current is restored within a few tens of milliseconds. This behaviour is in stark contrast to that in human rods, where the circulating current is obliterated by a background that bleaches only a few percent of the pigment, and where full recovery following a large bleach takes at least 20 min, some 50,000 times more slowly than shown here for human cones.

Measuring the impact of venous leg ulcers on quality of life.

OBJECTIVE: To identify health-related quality-of-life (HRQoL) issues in patients with venous leg ulcers, with the aim of generating items for a treatment outcome measure. METHOD: Thirty-eight patients with venous leg ulcers were interviewed by a psychologist using a semi-structured guide; they also completed a HRQoL questionnaire (modified Skindex). Data from the questionnaire were examined to explore the impact of venous leg ulcers on patients' lives. Interview transcripts were analysed using qualitative methods to identify additional venous leg ulcer-specific HRQoL items. RESULTS: Skindex scores indicated that older patients had worse HRQoL (p<0.05), as did those with pain and non-healing ulcers. Ulcer duration and size did not correlate with HRQoL. Interviews revealed the following effects of ulceration: pain (80.5%); itching (69.4%); altered appearance (66.7%); loss of sleep (66.6%); functional limitation (58.3%); and disappointment with treatment (50%). Based on the interview transcripts, items were generated and discussed with an expert panel, with a view to including them in a venous leg ulcer-specific HRQoL questionnaire. CONCLUSION: Disease-specific HRQoL outcome measures should be considered when evaluating treatments for venous leg ulcers.

Research fraud: issues of which practitioners should be aware.

Treatment and care given to patients should be evidence-based, but research results based on fraudulent findings can have a serious impact on care. This paper examines how fraud may be perpetuated and discusses standards for robust research.

Prevalence of left ventricular systolic dysfunction and heart failure in high risk patients: community based epidemiological study.

OBJECTIVES: To determine the prevalence of left ventricular systolic dysfunction, and of heart failure due to different causes, in patients with risk factors for these conditions. DESIGN: Epidemiological study, including detailed clinical assessment, electrocardiography, and echocardiography. SETTING: 16 English general practices, representative for socioeconomic status and practice type. PARTICIPANTS: 1062 patients (66% response rate) with previous myocardial infarction, angina, hypertension, or diabetes. MAIN OUTCOME MEASURES: Prevalence of systolic dysfunction, both with and without symptoms, and of heart failure, in groups of patients with each of the risk factors. RESULTS: Definite systolic dysfunction (ejection fraction <40%) was found in 54/244 (22.1%, 95% confidence interval 17.1% to 27.9%) patients with previous myocardial infarction, 26/321 (8.1%, 5.4% to 11.6%) with angina, 7/388 (1.8%, 0.7% to 3.7%) with hypertension, and 12/208 (5.8%, 3.0% to 9.9%) with diabetes. In each group, approximately half of these patients had symptoms of dyspnoea, and therefore had heart failure. Overall rates of heart failure, defined as symptoms of dyspnoea plus objective evidence of cardiac dysfunction (systolic dysfunction, atrial fibrillation, or clinically significant valve disease) were 16.0% (11.6% to 21.2%) in patients with previous myocardial infarction, 8.4% (5.6% to 12.0%) in those with angina, 2.8% (1.4% to 5.0%) in those with hypertension, and 7.7% (4.5% to 12.2%) in those with diabetes. CONCLUSION: Many people with ischaemic heart disease or diabetes have systolic dysfunction or heart failure. The data support the need for trials of targeted echocardiographic screening, in view of the major benefits of modern treatment. In contrast, patients with uncomplicated hypertension have similar rates to the general population.

Impact of heart failure and left ventricular systolic dysfunction on quality of life: a cross-sectional study comparing common chronic cardiac and medical disorders and a representative adult population.

BACKGROUND: Heart failure and left ventricular systolic dysfunction (LVSD) are increasingly common disorders, with outcomes worse than many cancers. Evidence-based therapies, such as ACE inhibitors and beta-blockers, improve prognosis and symptoms, and reduce healthcare expenditure. However, despite the high prevalence and malignant prognosis, few studies have reported the impact of heart failure and LVSD on overall quality of life and, more crucially, have not researched the elderly or those in the community. METHODS: All patients attending the Echocardiographic Heart of England Screening (ECHOES) study of the prevalence of heart failure and LVSD in the community were assessed by clinical history and examination, electrocardiogram and echocardiography, and also completed the SF36 health status questionnaire. Quality of life in patients found to have heart failure, LVSD, and other cardiac and medical conditions are compared with the randomly selected general population sample. Data are generalisable to the UK. RESULTS: 6162 people in the community were screened in the ECHOES study, of whom 5961 (97%) completed the SF36. The health perceptions of 3850 people aged 45 years or older selected randomly from the population were compared with those of 426 patients diagnosed as having definite heart failure. Those with heart failure had significant impairment of all the measured aspects of physical and mental health, in addition to declines in physical functioning. Significantly worse impairment was found in those with more severe heart failure by NYHA class: indeed, NYHA functional class was closely correlated to SF36 score. Patients with asymptomatic left ventricular dysfunction and patients rendered asymptomatic by treatment had similar scores to the random population sample. Those with heart failure reported more severe physical impairment of quality of life than people giving a history of chronic lung disease or arthritis, with less impact on mental health than patients reporting depression. CONCLUSIONS: Patients with heart failure have statistically significant impairment of all aspects of quality of life, not simply physical functioning. The physical (role and functioning) health burden was significantly greater than that suffered in other serious common chronic disorders, whether cardiac or other systems. Optimising treatment to improve NYHA class appears to improve perceptions of quality of life for patients with heart failure. Given the dramatic decline in quality of life with heart failure, this end-point should be a much more important target for healthcare interventions, especially treatments such as ACE inhibitors and beta-blockers that are shown to improve quality of life.

Reliability of N-terminal pro-brain natriuretic peptide assay in diagnosis of heart failure: cohort study in representative and high risk community populations.

OBJECTIVE: To investigate the performance of a novel assay for N-terminal pro-brain natriuretic peptide (NT-proBNP) in diagnosing heart failure in various randomly selected general and high risk community populations. DESIGN: Community cohort study (substudy of the echocardiographic heart of England screening study). SETTING: Four randomly selected general practices in the West Midlands of England. PARTICIPANTS: 591 randomly sampled patients over the age of 45, stratified for age and socioeconomic status and falling into four cohorts (general population, patients with an existing clinical label of heart failure, patients prescribed diuretics, and patients deemed at high risk of heart failure). MAIN OUTCOME MEASURE: Sensitivity, specificity, positive and negative predictive values, likelihood ratios, and area under receiver operating characteristic curve for NT-proBNP assay in the diagnosis of heart failure. RESULTS: For NT-proBNP in the diagnosis of heart failure in the general population (population screen), a level of >36 pmol/l had a sensitivity of 100%, a specificity of 70%, a positive predictive value of 7%, a negative predictive value of 100%, and an area under the receiver operating characteristic curve of 0.92 (95% confidence interval 0.82 to 1.0). Similar negative predictive values were found for patients from the three other populations screened. CONCLUSIONS: This NT-proBNP assay seems to have value in the diagnosis of heart failure in the community. High negative predictive values indicate that the assay's chief use would be to rule out heart failure in patients with suspected heart failure with normal concentrations of NT-proBNP. Positive results may identify patients who need cardiac imaging.

Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study.

BACKGROUND: Accurate data for prevalence rates for heart failure due to various causes, and for left-ventricular systolic dysfunction in all adults are unavailable. Our aim was to assess prevalence of left-ventricular systolic dysfunction and heart failure in a large representative adult population in England. METHODS: Of 6286 randomly selected patients aged 45 years and older, 3960 (63%) participated in the study. They came from 16 randomly selected general practices. We assessed patients by history and examination, electrocardiography, and echocardiography. Prevalence of left-ventricular systolic dysfunction (defined as ejection fraction <40%) and heart failure was calculated for the overall population on the basis of strict criteria and, when necessary, adjudication by a panel. FINDINGS: Left-ventricular systolic dysfunction was diagnosed in 72 (1.8% [95% CI 1.4-2.3]) participants, half of whom had no symptoms. Borderline left-ventricular function (ejection fraction 40-50%) was seen in 139 patients (3.5% [3.0-4.1]). Definite heart failure was seen in 92 (2.3%, [1.9-2.8]) and was associated with an ejection fraction of less than 40% in 38 (41%) patients, atrial fibrillation in 30 (33%), and valve disease in 24 (26%). Probable heart failure was seen in a further 32 (0.8% [0.6-1.1]) patients. In total, 124 (3.1% [2.6-3.7]) patients aged 45 years or older had definite or probable heart failure. INTERPRETATION: Heart failure is often misdiagnosed or underdiagnosed in primary care. Our results suggest that assessment of left-ventricular function in patients with suspected heart failure could lead to more effective diagnosis and treatment of this disorder.

Career pathways in research: support and management.

This article, the third in the series on career pathways, highlights support and management careers open to nurses working in the NHS and research and development, or people working for funding bodies or charitable organisations. These roles involve ensuring that the right infrastructure is in place to support research projects, and the correct decisions are made about which research projects should be supported and commissioned.

Career pathways in research: clinical research.

This article, the second in a series on career pathways, informs readers of the knowledge they require to conduct clinical therapeutic trials to recognised standards. Many nurses start their careers in research as clinical research nurses. The skills and knowledge they develop through conducting multi-centre studies gives them an excellent grounding in the discipline, organisation and management of research.

Career pathways in research: pharmaceutical.

The pharmaceutical pathway is the final article in this series on career pathways and highlights opportunities for nurses within associated industries. This pathway shows that nurses can use their nursing qualifications, combined with their knowledge, skills and expertise, to develop a career within another sphere of employment.

Career pathways in research: academic.

The academic pathway is the fourth in this series on career pathways and might be considered the most traditional career related to research. However, as is demonstrated in this series, research is every nurse's business and not a discipline to be conducted solely through academic institutions.

Undertaking leg ulcer research in primary care.

Evidence-based practice has become a by-word in leg ulcer care, but the picture is far from complete. More research is needed. Carrying out the research to ensure quality care in a primary care setting brings practical difficulties and raises issues which must be resolved, as a research team from Birmingham University shows.

Patient attitudes to over-the-counter drugs and possible professional responses to self-medication.

BACKGROUND: There is a paucity of research about patients' attitudes towards their doctor's recommending over-the-counter (OTC) remedies or about how patients respond to the doctor's suggestion to try an OTC remedy. OBJECTIVES: The aim of this study was to ascertain the attitudes of patients to OTC drugs. METHODS: 505 consecutive patients from each of six participating practices filled in a questionnaire. RESULTS: A total of 2765 (91.3%) patients responded. The responses from 2624 patients were from adults and are presented here. Based on the number of valid responses to each question, 53.8% of these patients were exempt from prescription charges, 55.1% took regular prescribed medication and 24.6% stated that they used OTC remedies regularly. There were generally positive attitudes to doctors enquiring about prior OTC use as well as to doctors making OTC recommendations in the consultation. However, patients expressed fairly negative attitudes towards pharmacists making generic substitutions and were even more hostile to the idea that pharmacists should make therapeutic substitutions. CONCLUSION: In conclusion, GPs should consider asking their patients regularly about their use of OTC medicines and also consider recommending OTC use if this is cheaper than FP10s. However, the public at present do not appear to be prepared for interventions by the pharmacist.