Systematic review and meta-analysis of enhanced recovery programmes in surgical patients.

BACKGROUND: Enhanced recovery programmes (ERPs) have been developed over the past 10 years to improve patient outcomes and to accelerate recovery after surgery. The existing literature focuses on specific specialties, mainly colorectal surgery. The aim of this review was to investigate whether the effect of ERPs on patient outcomes varies across surgical specialties or with the design of individual programmes. METHODS: MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials were searched from inception to January 2013 for randomized or quasi-randomized trials comparing ERPs with standard care in adult elective surgical patients. RESULTS: Thirty-eight trials were included in the review, with a total of 5099 participants. Study design and quality was poor. Meta-analyses showed that ERPs reduced the primary length of stay (standardized mean difference -1·14 (95 per cent confidence interval -1·45 to -0·85)) and reduced the risk of all complications within 30 days (risk ratio (RR) 0·71, 95 per cent c.i. 0·60 to 0·86). There was no evidence of a reduction in mortality (RR 0·69, 95 per cent c.i. 0·34 to 1·39), major complications (RR 0·95, 0·69 to 1·31) or readmission rates (RR 0·96, 0·59 to 1·58). The impact of ERPs was similar across specialties and there was no consistent evidence that elements included within ERPs affected patient outcomes. CONCLUSION: ERPs are effective in reducing length of hospital stay and overall complication rates across surgical specialties. It was not possible to identify individual components that improved outcome. Qualitative synthesis may be more appropriate to investigate the determinants of success.

Economic modelling of diagnostic and treatment pathways in National Institute for Health and Care Excellence clinical guidelines: the Modelling Algorithm Pathways in Guidelines (MAPGuide) project.

BACKGROUND: National Institute for Health and Care Excellence (NICE) clinical guidelines (CGs) make recommendations across large, complex care pathways for broad groups of patients. They rely on cost-effectiveness evidence from the literature and from new analyses for selected high-priority topics. An alternative approach would be to build a model of the full care pathway and to use this as a platform to evaluate the cost-effectiveness of multiple topics across the guideline recommendations. OBJECTIVES: In this project we aimed to test the feasibility of building full guideline models for NICE guidelines and to assess if, and how, such models can be used as a basis for cost-effectiveness analysis (CEA). DATA SOURCES: A 'best evidence' approach was used to inform the model parameters. Data were drawn from the guideline documentation, advice from clinical experts and rapid literature reviews on selected topics. Where possible we relied on good-quality, recent UK systematic reviews and meta-analyses. REVIEW METHODS: Two published NICE guidelines were used as case studies: prostate cancer and atrial fibrillation (AF). Discrete event simulation (DES) was used to model the recommended care pathways and to estimate consequent costs and outcomes. For each guideline, researchers not involved in model development collated a shortlist of topics suggested for updating. The modelling teams then attempted to evaluate options related to these topics. Cost-effectiveness results were compared with opinions about the importance of the topics elicited in a survey of stakeholders. RESULTS: The modelling teams developed simulations of the guideline pathways and disease processes. Development took longer and required more analytical time than anticipated. Estimates of cost-effectiveness were produced for six of the nine prostate cancer topics considered, and for five of eight AF topics. The other topics were not evaluated owing to lack of data or time constraints. The modelled results suggested 'economic priorities' for an update that differed from priorities expressed in the stakeholder survey. LIMITATIONS: We did not conduct systematic reviews to inform the model parameters, and so the results might not reflect all current evidence. Data limitations and time constraints restricted the number of analyses that we could conduct. We were also unable to obtain feedback from guideline stakeholders about the usefulness of the models within project time scales. CONCLUSIONS: Discrete event simulation can be used to model full guideline pathways for CEA, although this requires a substantial investment of clinical and analytic time and expertise. For some topics lack of data may limit the potential for modelling. There are also uncertainties over the accessibility and adaptability of full guideline models. However, full guideline modelling offers the potential to strengthen and extend the analytical basis of NICE's CGs. Further work is needed to extend the analysis of our case study models to estimate population-level budget and health impacts. The practical usefulness of our models to guideline developers and users should also be investigated, as should the feasibility and usefulness of whole guideline modelling alongside development of a new CG. FUNDING: This project was funded by the Medical Research Council and the National Institute for Health Research through the Methodology Research Programme [grant number G0901504] and will be published in full in Health Technology Assessment; Vol. 17, No. 58. See the NIHR Journals Library website for further project information.

Phenolic content and antioxidant capacity of hybrid variety cocoa beans.

Cocoa (Theobroma cacao L.) is a major, economically important, international crop and has been associated with several nutritional benefits including high antioxidant capacity. New cocoa hybrids have been developed in Ghana that exhibit resistance to pest damage during storage. The aim of this work was to assess the phenolic content and antioxidant capacity of these new hybrids in comparison to more traditional cocoa varieties. Total extractable phenolics were similar in all the four hybrids tested ranging from 69.9 to 81.6FAEg(-1). These levels were very similar to that extracted from traditional beans (73.8±2.5FAEg(-1)). The "phenolic profile" was determined by HPLC. A total of 25 peaks was observed but there were only minor differences in this profile between traditional and hybrid bean extracts. Antioxidant capacity was determined using the FRAP assay and traditional beans were found to possess 12.4µmolTEg(-1). In comparison the hybrid beans had antioxidant capacities ranging from 21.6 to 45.5µmolTEg(-1), and these were significantly higher than in the traditional beans for three out of the four hybrids. Since the phenolic and antioxidant levels and in these hybrid varieties were either similar to, or higher than, that obtained from traditional beans, the introduction of these new varieties would be unlikely to impact detrimentally on these nutritional components of the beans.

A comparative study of thoracic radiation doses from 64-slice cardiac CT.

The goal of this study was to measure radiation doses for 64-slice cardiac CT angiography studies and to study the dose-savings features of these CT scanners. This was done using various phantoms. These radiation doses were compared with those from typical helical body CT scans, fluoroscopy cardiac catheterization studies and mammography examinations. Radiation measurements were made with a CT ionization detector and a solid state dosimeter. A GE 64-slice Lightspeed VCT and a Siemens Somatom Sensation 64 CT were used to scan a standard 32 cm acrylic phantom and an anthropomorphic phantom. Data were collected in axial and various gated cardiac helical modes. Organ doses and the effective doses were calculated from the measurements. In gated CT cardiac mode with the 32 cm acrylic phantom, the measured radiation doses per study were generally three to seven times greater than those from typical body helical CT examinations; the range depended upon selectable scan parameters. With the anatomical phantom, the surface doses in the anteroposterior (AP) plane were typically 20-60% higher than those measured using the 32 cm phantom. The lateral surface doses were -4% to +15%. These results can be attributed to the shorter AP dimension and the air in the lungs. The CT skin entrance radiation doses were 80-90% less than diagnostic cardiac catheterization studies, and organ doses were similar. Because 64-slice cardiac gated CT uses pitches equal to 0.20-0.27 and high mAs values, the patient radiation doses are appreciably higher than in routine body CT examinations. The female breast, which could receive a radiation dose 10-30 times that received from mammography screening, is an organ of particular concern.

Children as partners with adults in their medical care.

AIMS: To investigate the seldom published views of children with type 1 diabetes about their condition and ways in which they share in managing their medical and health care with adults. METHODS: Semi-structured, tape recorded interviews, during 2003, with a purposive sample of 24 children aged 3-12 years who have type I diabetes and who attend two inner London hospitals and one hospital in a commuter town. RESULTS: The children reported high levels of understanding, knowledge, and skill gained from their experience of living with diabetes and constantly having to take account of the condition and their paediatrician's guidance. Their key goals were to be "normal" and "just get on with their lives". DISCUSSION: The interviews showed that children's experiences of diabetes tended to enable them to make informed, "wise" decisions in their own best interests, even at a young age. They achieved a complicated balance between the sometimes competing goals of social health "being normal" and physiological health in controlling glycaemia. Their competence supports approaches in children's rights and in policy makers' aims that people with diabetes--including children--gain more knowledge, skills, and responsibility for their own care in partnership with healthcare professionals. Consent is usually considered in relation to surgery; however the children showed how they constantly dealt with decisions about consent or refusal, compliance with, or resistance to their prescribed treatment. Their health depends on their informed commitment to medical guidance; more research is needed about the daily realities of children's committed and responsible co-management of their chronic illness.

Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia.

BACKGROUND: Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells. Repeated transfusions results in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. Desferrioxamine is the most widely used iron chelator. Substantial data have shown the beneficial effects of desferrioxamine. However, important questions exist about whether desferrioxamine is the best schedule for iron chelation therapy. OBJECTIVES: To determine the effectiveness (dose and method of administration) of desferrioxamine in people with transfusion-dependent thalassaemia. SEARCH STRATEGY: We searched the Cochrane Haemoglobinopathies Trials Register, MEDLINE, EMBASE, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We also contacted the manufacturers of desferrioxamine and other iron chelators. Date of last searches: April 2004. SELECTION CRITERIA: Randomised controlled trials comparing desferrioxamine with placebo; with another iron chelator; or comparing two schedules of desferrioxamine, in people with transfusion-dependent thalassaemia. DATA COLLECTION AND ANALYSIS: Four authors working independently, were involved in trial quality assessment and data extraction. Missing data were requested from the original investigators. MAIN RESULTS: Eight trials involving 334 people (range 20 to 144 people) were included. One trial compared desferrioxamine with placebo, five compared desferrioxamine with another iron chelator (deferiprone) and two compared different schedules of desferrioxamine. Overall, few trials measured the same outcomes.Compared to placebo, desferrioxamine significantly reduced iron overload. The number of deaths at 12 years follow up and evidence of reduced end-organ damage was less for desferrioxamine than placebo. When desferrioxamine was compared to deferiprone or a different desferrioxamine schedule there were no statistically significant differences in measures of iron overload. Compliance was recorded by two trials. Compliance was less for desferrioxamine than deferiprone in one trial and of no difference in comparison with desferrioxamine and deferiprone combined with a second trial. Adverse events were recorded in trials comparing desferrioxamine with other iron chelators. There was evidence of adverse events in all treatment groups. In one trial, adverse events were significantly less likely with desferrioxamine than deferiprone, relative risk 0.45 (95% confidence interval 0.24 to 0.84). Assessment of the methodological quality of included trials was not possible, given the general absence of these data in the trials. AUTHORS' CONCLUSIONS: We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Colloids versus crystalloids for fluid resuscitation in critically ill patients.

BACKGROUND: Colloid solutions are widely used in fluid resuscitation of critically ill patients. There are several choices of colloid and there is ongoing debate about the relative effectiveness of colloids compared to crystalloid fluids. OBJECTIVES: To assess the effects on mortality of colloids compared to crystalloids for fluid resuscitation in critically ill patients. SEARCH STRATEGY: We searched the Injuries Group specialised register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and BIDS Index to Scientific and Technical Proceedings, and checked reference lists of trials and review articles. SELECTION CRITERIA: All randomised and quasi-randomised trials of colloids compared to crystalloids, in patients requiring volume replacement. Cross-over trials and trials in pregnant women and neonates were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and rated quality of allocation concealment. Trials with a 'double-intervention', such as those comparing colloid in hypertonic crystalloid to isotonic crystalloid, were analysed separately. The analysis was stratified according to colloid type and quality of allocation concealment. MAIN RESULTS: Colloids compared to crystalloidsAlbumin or plasma protein fraction. Nineteen trials reported data on mortality, including a total of 7576 patients. The pooled relative risk (RR) from these trials was 1.02 (95% confidence interval [95% CI] 0.93 to 1.11). When the trial with poor quality allocation concealment was excluded, pooled RR was 1.01 (95% CI 0.92 to 1.10). Hydroxyethyl starch. Ten trials compared hydroxyethyl starch with crystalloids, including a total of 374 randomised participants. The pooled RR was 1.16 (95% CI 0.68 to 1.96). Modified gelatin. Seven trials compared modified gelatin with crystalloid, including a total of 346 randomised participants. The pooled RR was 0.54 (95% CI 0.16 to 1.85). Dextran. Nine trials compared dextran with a crystalloid, including a total of 834 randomised participants. The pooled relative risk was RR 1.24 (95% CI 0.94 to 1.65). Colloids in hypertonic crystalloid compared to isotonic crystalloidEight trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1283 randomised participants. Pooled RR was 0.88 (95% CI 0.74 to 1.05). REVIEWERS' CONCLUSIONS: There is no evidence from randomised controlled trials that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery. As colloids are not associated with an improvement in survival, and as they are more expensive than crystalloids, it is hard to see how their continued use in these patients can be justified outside the context of randomised controlled trials.

Prenatal screening and genetics.

Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were more precisely observed.

Early retardation of 99mTc-DTPA radioaerosol transalveolar clearance in irradiated canine lung.

UNLABELLED: The alteration of 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) transalveolar clearance in an initial phase of radiation lung injury was experimentally investigated. METHODS: Fourteen dogs were irradiated to the hemithorax with a single dose of 20 Gy. A DTPA radioaerosol study was performed before irradiation and on day 12 after irradiation. On day 14, the DTPA study was repeated again, with seven animals undergoing the study after inhalation of an aerosolized synthetic surfactant. The penetration index (P.I.) and clearance half-time (T(1/2)) of DTPA were measured in each lung. To evaluate the changes in lung surfactant after irradiation, alveolar lipids were stained in the resected lungs (n = 14), and the amounts of alveolar surfactant phospholipid and protein were measured by a bronchoalveolar lavage study in another six irradiated dogs. RESULTS: In all of the 14 irradiated animals, DTPA radioaerosol distributed uniformly throughout the lungs without significant changes in P.I. The T(1/2) values in irradiated lungs were significantly prolonged compared with the matched baseline values and those in nonirradiated lungs (P < 0.05 and 0.001, respectively). The aerosolized synthetic surfactant retarded the DTPA clearance both in the irradiated and in the nonirradiated lungs (P < 0.001) without significant changes in P.I. The histologic and bronchoalveolar lavage studies revealed an increase of alveolar surfactant materials in the irradiated lungs without substantial histologic changes in the alveolar structures. CONCLUSION: DTPA transalveolar clearance was retarded soon after irradiation. Increased alveolar surfactant may be partly responsible for this retarded DTPA clearance because the aerosolized synthetic surfactant also prolonged the clearance in nonirradiated lungs. A DTPA clearance test is sensitive for the early detection of radiation lung injury and seems helpful for clarifying the association of epithelial integrity changes and lung surfactant in radiation lung injury.

Rapid in vivo monitoring of chemotherapeutic response using weighted sodium magnetic resonance imaging.

A novel pulse sequence strategy uses sodium magnetic resonance imaging to monitor the response to chemotherapy of mouse xenograft tumors propagated from human prostate cancer cell lines. An inversion pulse suppresses sodium with long longitudinal relaxation times, weighting the image toward intracellular sodium nuclei. Comparing these weighted sodium images before and 24 h after administration of antineoplastics, we measured a 36 +/- 4% (P < 0.001; n = 16) increase in signal intensity. Experiments with these same drugs and cells, treated in culture, detected a significant intracellular sodium elevation (10-20 mM) using a ratiometric fluorescent dye. Flow cytometry studies showed that this elevation preceded cell death by apoptosis, as determined by fluorescent end-labeling of apoptotic nuclei or Annexin V binding. Histopathology on formalin-fixed sections of explanted tumors confirmed that drug administration reduces proliferation (2.2 versus 8.6 mitotic figures per high power field; P < 0.0001), an effect that inversely correlates with the sodium magnetic resonance image response on a tumor-to-tumor basis (P < 0.02; n = 10). Morphological features, such as central zones of nonviable cells, rims of active apoptosis, and areas of viable tumor, could be distinguished by comparing weighted and unweighted images. Advantages of this sodium imaging technique include rapid determination of drug efficacy, improved diagnosis of lesions, ease of coregistration with high resolution proton magnetic resonance imaging, and absence of costly or toxic reagents.

Colloids versus crystalloids for fluid resuscitation in critically ill patients.

BACKGROUND: Colloid solutions are widely used in fluid resuscitation of critically ill patients. There are several choices of colloid and there is ongoing debate about the relative effectiveness of colloids compared to crystalloid fluids. OBJECTIVES: To assess the effects on mortality of colloids compared to crystalloids for fluid resuscitation in critically ill patients. SEARCH STRATEGY: We searched the Injuries Group specialised register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and BIDS Index to Scientific and Technical Proceedings and checked the reference lists of trials and review articles. SELECTION CRITERIA: All randomised and quasi-random trials of colloids compared to crystalloids, in patients requiring volume replacement. Cross-over trials and trials in pregnant women and neonates were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and rated quality of allocation concealment. Trials with a 'double-intervention' such as those, which compared colloid in hypertonic crystalloid to isotonic crystalloid, were analysed separately. The analysis was stratified according to colloid type and quality of allocation concealment. MAIN RESULTS: Colloids compared to crystalloids: Albumin or plasma protein fraction: Eighteen trials reported data on mortality, including a total of 641 patients. The pooled relative risk from these trials was 1.52 (95% confidence interval 1.08 to 2.13). The risk of death in the albumin treated group was 6% higher than in the crystalloid treated group (1% to 11%). When the trial with poor quality allocation concealment was excluded the pooled relative risk was 1.34 (0.95 to 1.89). Hydroxyethylstarch: Seven trials compared hydroxyethylstarch with crystalloids including a total of 197 randomised participants. The pooled relative risk was 1.16 (0.68 to 1.96). Modified gelatin: Four trials compared modified gelatin with crystalloid including a total of 95 randomised participants. The pooled relative risk was 0.50 (0. 08 to 3.03). Dextran: Eight trials compared dextran with a crystalloid including a total of 668 randomised participants. The pooled relative risk was 1.24 (0.94 to 1.65). Colloids in hypertonic crystalloid compared to isotonic crystalloid: Eight trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1283 randomised participants. The pooled relative risk was 0.88 (0.74 to 1.05). REVIEWER'S CONCLUSIONS: There is no evidence from randomised controlled trials that resuscitation with colloids reduces the risk of death compared to crystalloids in patients with trauma, burns and following surgery. As colloids are not associated with an improvement in survival, and as they are more expensive than crystalloids, it is hard to see how their continued use in these patient types can be justified outside the context of randomised controlled trials.

Doctors, ethics and special education.

This discussion paper is drawn from a qualitative research project comparing the effect of special and ordinary schools on the lives of children, young people and their families. Special schools are recommended by health professionals who seldom know how ineffective these schools are. We question the beneficence and justice of health professionals' advice on education for children with disabilities and other difficulties. Cooperation with local education authorities (LEAs) plays a considerable part in the work of community paediatricians, clinical medical officers, therapists and other health professionals encountering children with "special needs". The "needs" range from physical disability and sensory impairment to learning difficulties and emotional or behavioural difficulties. This cooperation involves routine administrative problems, but it raises broad ethical issues too, particularly in respect of current tendencies in state schooling towards the integration or inclusion of these children in mainstream schools and classes.

Equipoise as a means of managing uncertainty: personal, communal and proxy.

Equipoise is advocated as a means of achieving high scientific and ethical standards in randomised trials. As used in the context of research the word describes a state of uncertainty characterised by the belief that in a trial no arm is known to offer greater harm or benefit than any other arm. Clinicians who lack personal equipoise are advised to accept clinical or communal equipoise, based on current unresolved disagreement among the medical profession. Equipoise is mainly discussed in the literature as an issue for senior doctors and research directors. Limitations of professional equipoise are reviewed, and data on the neglected topic of patients' equipoise are reported using the example of breast cancer trials. In theory, a patient who gives informed and voluntary consent to enter a randomised trial has achieved the equilibrium of equipoise. In practice, equipoise among patients ranges from personal to proxy acceptance.

Consent to surgery: the role of the nurse.

In the first of two articles relating to consent issues, the author examines the role of the nurse in helping patients to have a more equal relationship with doctors when they sign a consent form. It is based on sociological research studies of consent to surgery (1-3). Next week, the author will look at issues relating to consent to research.

Nursing ethics. Consent to research: the role of the nurse.

Last week, the author considered the problems nurses face when helping patients to give informed consent to surgery. This week the author looks at the consent issues faced by nurses caring for patients involved in clinical research. The problems associated with consent to research can be even more complex than those relating just to surgery. This article reviews ways of tackling them.

Oral premedication for paediatric ambulatory anaesthesia: a comparison of midazolam and ketamine.

To compare the clinical characteristics of two oral premedicants, midazolam and ketamine, 40 healthy children, one to six years of age, who were scheduled for ambulatory dental surgery, were assigned to receive either oral midazolam 0.5 mg.kg-1 or oral ketamine 5.0 mg.kg-1 in a double-blind, randomized study. Sedation and anxiolysis scores before induction, cooperation at induction of anaesthesia and recovery times and complications were assessed. We found that both drugs effectively sedated the children within 20 min of administration. Although sedated, 10% of the children in the midazolam group and 20% of those in the ketamine group became tearful on separation from their parents and 20% of those in the midazolam group and 35% of those in the ketamine group became tearful when the facemask was applied. No important side effects were attributable to either premedication. The time until the children were fit for discharge from the hospital after midazolam was approximately 20 min less than after ketamine. In conclusion, midazolam and ketamine offer similar clinical characteristics when used as oral premedications for children undergoing ambulatory surgery, although the time to discharge from hospital may be more rapid after midazolam than after ketamine.

In the genes or in the stars? Children's competence to consent.

Children's competence to refuse or consent to medical treatment or surgery tends to be discussed in terms of the child's ability or maturity. This paper argues that the social context also powerfully influences the child's capacity to consent. Inner attributes and external influences are discussed using an analogy of the genes and the stars.