Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study.

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.

Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

A pilot study of cardiopulmonary exercise testing and cardiac stress positron emission tomography before major non-cardiac surgery.

Cardiac events are a common cause of peri-operative morbidity. Cardiopulmonary exercise testing can objectively assess risk, but it does not quantify myocardial ischaemia. With appropriate dietary preparation to suppress basal myocardial glucose uptake, positron emission tomography with 18 F-fluorodeoxyglucose can identify post-ischaemic myocardium, providing an attractive complement to exercise testing. We aimed to investigate the feasibility of this diagnostic algorithm. Patients referred for cardiopulmonary exercise testing before major cancer surgery were prospectively recruited. Exercise testing and positron emission tomography imaging were performed after a high fat-low carbohydrate meal. Protocol feasibility (primary end-point) included compliance with pre-test diet instructions and the completion of tests. Stress myocardial perfusion imaging was performed if either exercise testing or positron emission tomography was equivocal or positive for ischaemia. We recorded cardiac complications for 30 postoperative days. We enrolled 26 participants, 20 of whom completed protocol. Twenty-one participants proceeded to surgery: myocardial injury or infarction was diagnosed in three participants, two of whom had positive or equivocal positron emission tomography but negative myocardial perfusion imaging. We have shown that pre-operative cardiac positron emission tomography after cardiopulmonary exercise testing is feasible; protocol deviations were minor and did not affect image quality. Our findings warrant further investigation to compare the diagnostic utility of cardiac positron emission tomography imaging with standard pre-operative stress tests.

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Genetic testing in inherited polyposis syndromes - how and why?

There have been recent advances in genetic testing enabling accurate diagnosis of polyposis syndromes by identifying causative gene mutations, which is essential in the management of individuals with polyposis syndrome and predictive genetic testing of their extended families. There are some similarities in clinical presentation of various polyposis syndromes, which may pose a challenge to diagnosis. In this review, we discuss the clinical presentation of the main polyposis syndromes and the process of genetic testing, including the latest advancement and future of genetic testing. We aim to reiterate the importance of genetic testing in the management of polyposis syndromes, potential pitfalls associated with genetic testing and recommendations for healthcare professionals involved with the care of polyposis patients.

Temperature dependence of the electronic structure and Fermi-surface reconstruction of Eu(1-x)Gd(x)O through the ferromagnetic metal-insulator transition.

We present angle-resolved photoemission spectroscopy of Eu(1-x)Gd(x)O through the ferromagnetic metal-insulator transition. In the ferromagnetic phase, we observe Fermi surface pockets at the Brillouin zone boundary, consistent with density functional theory, which predicts a half-metal. Upon warming into the paramagnetic state, our results reveal a strong momentum-dependent evolution of the electronic structure, where the metallic states at the zone boundary are replaced by pseudogapped states at the Brillouin zone center due to the absence of magnetic long-range order of the Eu 4f moments.

COPD prevalence and its association with occupational exposures in a general population.

The aim of this study was to ascertain the population prevalence of chronic obstructive pulmonary disease (COPD) in an area with past heavy industry and to establish the relative contributions of occupational and other risk factors. We investigated respiratory symptoms and the prevalence of spirometrically-defined COPD in a population-based study in North-East England (UK) between 2002 and 2004. Questionnaires were posted to 6,000 males and 6,000 females, 45-69 yrs of age, who were randomly selected from a primary care database (response rate 64%, n = 7,566). Spirometric measurements were performed on 845 randomly selected responders. We defined COPD by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) II criteria. The prevalence of respiratory symptoms was 55%. Symptoms were strongly associated with smoking, occupational exposures and hay fever. COPD was present in 10% of subjects. Its presence was significantly associated with occupational exposures, smoking and hay fever. COPD is common in North-East England. Respiratory effects of occupational exposures can be detected within the general population: there were clear associations between occupational exposures and respiratory symptoms. The association with COPD was more marked in females.

Is there an intrinsic limit to the charge-carrier-induced increase of the Curie temperature of EuO?

Rare earth doping is the key strategy to increase the Curie temperature (T(C)) of the ferromagnetic semiconductor EuO. The interplay between doping and charge carrier density (n), and the limit of the T(C) increase, however, are yet to be understood. We report measurements of n and T(C) of Gd-doped EuO over a wide range of doping levels. The results show a direct correlation between n and T(C), with both exhibiting a maximum at high doping. On average, less than 35% of the dopants act as donors, raising the question about the limit to increasing T(C).

Generating spatially entangled itinerant photons with waveguide quantum electrodynamics.

Realizing a fully connected network of quantum processors requires the ability to distribute quantum entanglement. For distant processing nodes, this can be achieved by generating, routing, and capturing spatially entangled itinerant photons. In this work, we demonstrate the deterministic generation of such photons using superconducting transmon qubits that are directly coupled to a waveguide. In particular, we generate two-photon N00N states and show that the state and spatial entanglement of the emitted photons are tunable via the qubit frequencies. Using quadrature amplitude detection, we reconstruct the moments and correlations of the photonic modes and demonstrate state preparation fidelities of 84%. Our results provide a path toward realizing quantum communication and teleportation protocols using itinerant photons generated by quantum interference within a waveguide quantum electrodynamics architecture.

Effective health care: management of head and neck cancers.

The management of head and neck cancer, published in a recent issue of Effective Health Care, is reviewed.

Sintered hydroxyfluorapatites--IV: The effect of fluoride substitutions upon colonisation of hydroxyapatites by mouse embryonic stem cells.

Biodegradable scaffolds serve a central role for tissue engineering scaffolds and guiding tissue regeneration. Some of these scaffolds, including apatites, display a significant effect upon cell adhesion and cell proliferation. The incorporation of scaffold technology with the developing embryonic stem (ES) cell field and the capacity of ES cells for self-renewal and differentiation are believed to hold enormous potential for applications in biomedical research and regenerative medicine. The purpose of this work was to determine the effect of hydroxyapatite (HAP) and fluoride substitutions of HAP upon ES cell growth and colonisation. Sintered hydroxyfluorapatite discs were found to support cellular proliferation and colonisation, and the ES cells displayed a tendency for differentiation on the apatite surface as determined by reductions in colony Oct4 immunoreactivity. Fluoride-containing HAPs were found to provide equivalent support to gelatin in terms of cell numbers, yet superior support for cellular colonisation when compared to HAP. This study indicates that fluoride substitutions of HAP may represent a viable strategy for the development of certain engineered tissue replacements and tissue regeneration systems using ES cells.

FDA advisory committees and the new drug approval process.

To determine the impact of FDA advisory committee review on the approval time of new drug applications (NDAs) approved during the five-year period 1983 through 1987, we compared NDA phase lengths of reviewed new chemical entities (NCEs) with those that were not reviewed and examined the elapsed time from final committee recommendation for approval to NDA approval. Of the 95 drugs approved during the study period that met the Center for the Study of Drug Development's definition of an NCE, 40 (42%) were submitted for review--mean NDA phase length was 36.9 months versus 32.4 months for unreviewed drugs. Reviewed drugs in the neuropharmacologic division had a longer NDA phase, while those in the metabolic/endocrine and oncology/radiopharmaceutical divisions had shorter NDA phases, than unreviewed drugs in those divisions. For NCEs grouped by therapeutic rating, reviewed drugs in each category had longer NDA phases than unreviewed drugs; the difference was largest for 1-B rated drugs. The elapsed time from committee recommendation for approval to NDA approval as a percent of the total NDA phase was greatest for drugs submitted by the metabolic/endocrine division (83.0% of NDA phase) and for drugs rated 1-A (63.2%). Results indicate that advisory committee review is associated with a small overall delay in NDA approval when compared with the regulatory fate of drugs not submitted for review.

Management of colorectal cancers.

The management of colorectal cancers, published in a recent issue of Effective Health Care, is reviewed.

Set and serendipity in the detection of drug hazards.

This paper deals with influences which affect the recognition of drug hazards and examines the policy implications of the analysis. Decision-making about the control of potentially dangerous medicines presents problems for policy makers. Action in this area provokes controversy because the interests of those concerned differ widely and because judgements are made in the face of uncertainty. The problem can be described in terms of models derived from signal detection theory. The signal (an adverse drug reaction, ADR) must be differentiated from background noise (disease due to other causes). This approach directs attention to the two general factors that influence detection: the discriminability of the signal and the observer's operating criterion. How clearly an ADR can be discriminated from other illness largely depends on the nature of the reaction, but the criterion is determined by social and behavioural forces including the costs and benefits of each type of decision. These in turn depend on the interests and attitudes of the institutions involved. It is concluded that detection of drug-induced disease is hampered by the attitudes of those charged with monitoring the effects of drugs. The shared assumption that medicines are good produces an excessively high criterion for the recognition of their dangers.

Palliative radiotherapy regimens for non-small cell lung cancer.

BACKGROUND: Palliative radiotherapy (RT) to the chest is often used in patients with lung cancer, but RT regimens are more often based on tradition than research results. OBJECTIVES: To discover the most effective and least toxic regimens of palliative RT, and whether higher doses increase survival. SEARCH STRATEGY: Electronic databases, reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished. SELECTION CRITERIA: Randomised controlled clinical trials comparing different regimens of palliative RT in patients with non-small lung cancer. DATA COLLECTION AND ANALYSIS: Ten randomised trials were reviewed. There were important differences in the doses of RT investigated, the patient characteristics and the outcome measures. Because of this heterogeneity no meta-analysis was attempted. MAIN RESULTS: There is no strong evidence that any regimen gives greater palliation. Higher dose regimens give more acute toxicity. There is evidence for a modest increase in survival (6% at 1 year and 3% at 2 years) in patients with better performance status (PS) given higher dose RT. REVIEWER'S CONCLUSIONS: The majority of patients should be treated with short courses of palliative RT, of 1 or 2 fractions. Care should be taken with the dose to the spinal cord. The use of high dose palliative regimens should be considered for and discussed with selected patients with good PS. More research is needed into reducing the acute toxicity of large fraction regimens and into the role of radical compared to high dose palliative RT and more homogeneous studies are needed.

Palliative radiotherapy regimens for non-small cell lung cancer.

BACKGROUND: Palliative radiotherapy (RT) to the chest is often used in patients with lung cancer, but RT regimens are more often based on tradition than research results. OBJECTIVES: To discover the most effective and least toxic regimens of palliative RT, and whether higher doses increase survival. SEARCH STRATEGY: Electronic databases, reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished. SELECTION CRITERIA: Randomised controlled clinical trials comparing different regimens of palliative RT in patients with non-small lung cancer. DATA COLLECTION AND ANALYSIS: Ten randomised trials were reviewed. There were important differences in the doses of RT investigated, the patient characteristics and the outcome measures. Because of this heterogeneity no meta-analysis was attempted. MAIN RESULTS: There is no strong evidence that any regimen gives greater palliation. Higher dose regimens give more acute toxicity. There is evidence for a modest increase in survival (6% at 1 year and 3% at 2 years) in patients with better performance status (PS) given higher dose RT. REVIEWER'S CONCLUSIONS: The majority of patients should be treated with short courses of palliative RT, of 1 or 2 fractions. Care should be taken with the dose to the spinal cord. The use of high dose palliative regimens should be considered for and discussed with selected patients with good PS. More research is needed into reducing the acute toxicity of large fraction regimens and into the role of radical compared to high dose palliative RT and more homogeneous studies are needed.

Health effects of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure: a systematic review of the research evidence.

OBJECTIVE: To examine the research evidence for the health consequences of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure. DESIGN: A systematic review of published research, studies being identified by searching Medline (1966-96), Embase (1974-96), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1982-95); scanning citations; and consulting experts. Studies in all languages were considered which either investigated the association between obstructive sleep apnoea in adults and key health outcomes or evaluated the effectiveness of treatment of obstructive sleep apnoea with continuous positive airways pressure in adults. MAIN OUTCOME MEASURES: Mortality, systematic hypertension, cardiac arrhythmias, ischaemic heart disease, left ventricular hypertrophy, pulmonary hypertension, stroke, vehicle accidents, measures of daytime sleepiness, and quality of life. RESULTS: 54 epidemiological studies examined the association between sleep apnoea and health related outcomes. Most were poorly designed and only weak or contradictory evidence was found of an association with cardiac arrhythmias, ischaemic heart disease, cardiac failure, systemic or pulmonary hypertension, and stroke. Evidence of a link with sleepiness and road traffic accidents was stronger but inconclusive. Only one small randomised controlled trial evaluated continuous positive airways pressure. Five non-randomised controlled trials and 38 uncontrolled trials were identified. Small changes in objectively measured daytime sleepiness were consistently found, but improvements in morbidity, mortality, and quality of life indicators were not adequately assessed. CONCLUSIONS: The relevance of sleep apnoea to public health has been exaggerated. The effectiveness of continuous positive airways pressure in improving health outcomes has been poorly evaluated. There is enough evidence suggesting benefit in reducing daytime sleepiness in some patients to warrant large randomised placebo controlled trials of continuous positive airways pressure versus an effective weight reduction programme and other interventions.

Managing primary breast cancer: a review of care.

This month's report from the NHS Centre for Reviews and Dissemination explains the key findings of the Effective Health Care Bulletin (Nuffield Institute for Health et al 1996) on the management of primary breast cancer. This bulletin was based on the results of a series of wide-ranging reviews that sought to answer a variety of questions about different aspects of care for breast cancer patients.

Why nurses must get involved in colorectal cancer management.

This article summarises guidance for the care of people with colorectal cancer based on systematic reviews carried out by the NHS Centre for Reviews and Dissemination (CRD). A broad range of issues was examined, leading to recommendations for treatment as well as for the organisation of services. A number of recommendations looked at the part that nurses can play in diagnosis, treatment and support of patients.