Summary Improvements in the control of haemorrhage after trauma have resulted in the survival of many people who would otherwise have died from the initial loss of blood. However, the danger is not ...over once bleeding has been arrested and blood pressure restored. Two-thirds of patients who die following major trauma now do so as a result of causes other than exsanguination. Trauma evokes a systemic reaction that includes an acute, non-specific, immune response associated, paradoxically, with reduced resistance to infection. The result is damage to multiple organs caused by the initial cascade of inflammation aggravated by subsequent sepsis to which the body has become susceptible. This Series examines the biological mechanisms and clinical implications of the cascade of events caused by large-scale trauma that leads to multiorgan failure and death, despite the stemming of blood loss. Furthermore, the stark and robust epidemiological finding—namely, that age has a profound influence on the chances of surviving trauma irrespective of the nature and severity of the injury—will be explored. Advances in our understanding of the inflammatory response to trauma, the impact of ageing on this response, and how this information has led to new and emerging treatments aimed at combating immune dysregulation and reduced immunity after injury will also be discussed.
Summary Massive slums have become major features of cities in many low-income and middle-income countries. Here, in the first in a Series of two papers, we discuss why slums are unhealthy places with ...especially high risks of infection and injury. We show that children are especially vulnerable, and that the combination of malnutrition and recurrent diarrhoea leads to stunted growth and longer-term effects on cognitive development. We find that the scientific literature on slum health is underdeveloped in comparison to urban health, and poverty and health. This shortcoming is important because health is affected by factors arising from the shared physical and social environment, which have effects beyond those of poverty alone. In the second paper we will consider what can be done to improve health and make recommendations for the development of slum health as a field of study.
Summary In the first paper in this Series we assessed theoretical and empirical evidence and concluded that the health of people living in slums is a function not only of poverty but of intimately ...shared physical and social environments. In this paper we extend the theory of so-called neighbourhood effects. Slums offer high returns on investment because beneficial effects are shared across many people in densely populated neighbourhoods. Neighbourhood effects also help explain how and why the benefits of interventions vary between slum and non-slum spaces and between slums. We build on this spatial concept of slums to argue that, in all low-income and-middle-income countries, census tracts should henceforth be designated slum or non-slum both to inform local policy and as the basis for research surveys that build on censuses. We argue that slum health should be promoted as a topic of enquiry alongside poverty and health.
Summary Background Colonoscopy is the gold-standard test for investigation of symptoms suggestive of colorectal cancer; computed tomographic colonography (CTC) is an alternative, less invasive test. ...However, additional investigation after CTC is needed to confirm suspected colonic lesions, and this is an important factor in establishing the feasibility of CTC as an alternative to colonoscopy. We aimed to compare rates of additional colonic investigation after CTC or colonoscopy for detection of colorectal cancer or large (≥10 mm) polyps in symptomatic patients in clinical practice. Methods This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for colonoscopy. Patients were randomly assigned (2:1) to colonoscopy or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome—the rate of additional colonic investigation—by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. Findings 1610 patients were randomly assigned to receive either colonoscopy (n=1072) or CTC (n=538). 30 patients withdrew consent, leaving for analysis 1047 assigned to colonoscopy and 533 assigned to CTC. 160 (30·0%) patients in the CTC group had additional colonic investigation compared with 86 (8·2%) in the colonoscopy group (relative risk 3·65, 95% CI 2·87–4·65; p<0·0001). Almost half the referrals after CTC were for small (<10 mm) polyps or clinical uncertainty, with low predictive value for large polyps or cancer. Detection rates of colorectal cancer or large polyps in the trial cohort were 11% for both procedures. CTC missed 1 of 29 colorectal cancers and colonoscopy missed none (of 55). Serious adverse events were rare. Interpretation Guidelines are needed to reduce the referral rate after CTC. For most patients, however, CTC provides a similarly sensitive, less invasive alternative to colonoscopy. Funding NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.
Summary Background Barium enema (BE) is widely available for diagnosis of colorectal cancer despite concerns about its accuracy and acceptability. Computed tomographic colonography (CTC) might be a ...more sensitive and acceptable alternative. We aimed to compare CTC and BE for diagnosis of colorectal cancer or large polyps in symptomatic patients in clinical practice. Methods This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for radiological investigation of the colon. Patients were randomly assigned (2:1) to BE or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome—diagnosis of colorectal cancer or large (≥10 mm) polyps—by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. Findings 3838 patients were randomly assigned to receive either BE (n=2553) or CTC (n=1285). 34 patients withdrew consent, leaving for analysis 2527 assigned to BE and 1277 assigned to CTC. The detection rate of colorectal cancer or large polyps was significantly higher in patients assigned to CTC than in those assigned to BE (93 7·3% of 1277 vs 141 5·6% of 2527, relative risk 1·31, 95% CI 1·01–1·68; p=0·0390). CTC missed three of 45 colorectal cancers and BE missed 12 of 85. The rate of additional colonic investigation was higher after CTC than after BE (283 23·5% of 1206 CTC patients had additional investigation vs 422 18·3% of 2300 BE patients; p=0·0003), due mainly to a higher polyp detection rate. Serious adverse events were rare. Interpretation CTC is a more sensitive test than BE. Our results suggest that CTC should be the preferred radiological test for patients with symptoms suggestive of colorectal cancer. Funding NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.
Evaluation and stages of surgical innovations Barkun, Jeffrey S, Prof; Aronson, Jeffrey K, Prof; Feldman, Liane S, MD ...
The Lancet (British edition),
2009-Sep-26, Letnik:
374, Številka:
9695
Journal Article
Recenzirano
Summary Surgical innovation is an important part of surgical practice. Its assessment is complex because of idiosyncrasies related to surgical practice, but necessary so that introduction and ...adoption of surgical innovations can derive from evidence-based principles rather than trial and error. A regulatory framework is also desirable to protect patients against the potential harms of any novel procedure. In this first of three Series papers on surgical innovation and evaluation, we propose a five-stage paradigm to describe the development of innovative surgical procedures.
Summary Surgery and other invasive therapies are complex interventions, the assessment of which is challenged by factors that depend on operator, team, and setting, such as learning curves, quality ...variations, and perception of equipoise. We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process. We also encourage the widespread use of prospective databases and registries. Reports of new techniques should be registered as a professional duty, anonymously if necessary when outcomes are adverse. Case series studies should be replaced by prospective development studies for early technical modifications and by prospective research databases for later pre-trial evaluation. Protocols for these studies should be registered publicly. Statistical process control techniques can be useful in both early and late assessment. Randomised trials should be used whenever possible to investigate efficacy, but adequate pre-trial data are essential to allow power calculations, clarify the definition and indications of the intervention, and develop quality measures. Difficulties in doing randomised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems. Alternative prospective designs, such as interrupted time series studies, should be used when randomised trials are not feasible. Established procedures should be monitored with prospective databases to analyse outcome variations and to identify late and rare events. Achievement of improved design, conduct, and reporting of surgical research will need concerted action by editors, funders of health care and research, regulatory bodies, and professional societies.
Challenges in evaluating surgical innovation Ergina, Patrick L, Dr; Cook, Jonathan A, PhD; Blazeby, Jane M, Prof ...
The Lancet,
09/2009, Letnik:
374, Številka:
9695
Journal Article
Recenzirano
Odprti dostop
Summary Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially ...demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures—for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.
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