Analgesic efficacy of ketamine and magnesium after laparoscopic sleeve gastrectomy: A randomized, double-blind, placebo-controlled trial.

Background Ketamine and magnesium are antagonists of the N-methyl-d-aspartate receptor, and are valuable adjuvants for multimodal analgesia and opioid sparing. Data are limited regarding the opioid sparing efficacy of the combined intraoperative application of these agents in laparoscopic bariatric surgery. The objective of this study was to compare the postoperative opioid sparing properties of a single intraoperative dose of ketamine versus a combination of single doses of ketamine and magnesium after laparoscopic gastric sleeve resection in bariatric patients. Methods One hundred and twenty- six patients were randomly assigned to receive single boluses of ketamine alone 0.5 mg kg-1 IV (ketamine group); combined ketamine bolus of 0.5 mg kg-1 IV and magnesium 2 g IV (ketamine and magnesium group); or placebo. Opioid consumption at 24 h (in morphine equivalents); pain at rest; postoperative nausea and vomiting impact score; sedation scores; and trends of transcutaneous carbon-di-oxide values were analysed. Results The median (inter-quartile range [range]) morphine consumption at 24 h were 32 (24-47 [4.8-91]) mg in the ketamine group, 37 (18-53 [1-144]) mg in the ketamine and magnesium group, and 26 (21-36 [5-89]) mg in the control group and were not significantly different between the groups. There were no differences for all other outcomes examined. Conclusion Combined single intraoperative bolus doses of ketamine and magnesium did not result in postoperative opioid sparing after laparoscopic gastric sleeve resection.

HORIZONS protocol: a UK prospective cohort study to explore recovery of health and well-being in adults diagnosed with cancer.

INTRODUCTION: Understanding the impact of cancer and its treatment on people's everyday lives will help prepare people for what to expect, enable health professionals to predict likely recovery trajectories and shape care management according to needs. HORIZONS will recruit people awaiting treatment and follow them up at regular intervals to assess recovery of health and well-being. RESEARCH QUESTIONS: What impact does cancer diagnosis and treatment have on people's lives in the short, medium and long term? What are people's health and well-being outcomes, experiences and self-management activities over time across different cancer types and what influences these? How do people connect with and relate to others in mobilising resources that enable them to self-manage the consequences of cancer and treatment? METHODS AND ANALYSIS: HORIZONS is a multicentre, prospective cohort study exploring recovery of health and well-being in 3000 people diagnosed with breast cancer (<50 years), non-Hodgkin's lymphoma or gynaecological cancer. Recruitment will take place across National Health Service (NHS) sites in the UK between September 2016 and March 2019, before primary treatment starts. Participants will be identified through clinical teams and invited to complete questionnaires including assessments of quality of life, symptoms and functioning (Quality of Life in Adult Cancer Survivors; European Organisation for Research and Treatment Consortium Core quality of life questionnaire, EORTC-QLQ-C30), health status (EuroQol-5 dimensions, EQ-5D), self-efficacy, social support, social networks and lifestyle. Clinical data will also be collected. Descriptive statistics will characterise outcomes. Changes over time will be investigated. Factors that may influence recovery and self-management will be included in regression models to determine which influence health and well-being and self-management. ETHICS AND DISSEMINATION: Ethics and Health Research Authority approvals granted (IRAS Project ID: 202342, REC reference number 16/NW/0425). Adopted onto the National Institute for Health Research Clinical Research Network portfolio. We will engage with our Scientific Advisory Board, Tumour Specific Expert Panels, User Reference Group, Macmillan and the University of Southampton to ensure maximum publicity and benefit.

Telehealth for patients at high risk of cardiovascular disease: pragmatic randomised controlled trial.

OBJECTIVE:  To assess whether non-clinical staff can effectively manage people at high risk of cardiovascular disease using digital health technologies. DESIGN:  Pragmatic, multicentre, randomised controlled trial. SETTING:  42 general practices in three areas of England. PARTICIPANTS:  Between 3 December 2012 and 23 July 2013 we recruited 641 adults aged 40 to 74 years with a 10 year cardiovascular disease risk of 20% or more, no previous cardiovascular event, at least one modifiable risk factor (systolic blood pressure ≥140 mm Hg, body mass index ≥30, current smoker), and access to a telephone, the internet, and email. Participants were individually allocated to intervention (n=325) or control (n=316) groups using automated randomisation stratified by site, minimised by practice and baseline risk score. INTERVENTIONS:  Intervention was the Healthlines service (alongside usual care), comprising regular telephone calls from trained lay health advisors following scripts generated by interactive software. Advisors facilitated self management by supporting participants to use online resources to reduce risk factors, and sought to optimise drug use, improve treatment adherence, and encourage healthier lifestyles. The control group comprised usual care alone. MAIN OUTCOME MEASURES:  The primary outcome was the proportion of participants responding to treatment, defined as maintaining or reducing their cardiovascular risk after 12 months. Outcomes were collected six and 12 months after randomisation and analysed masked. Participants were not masked. RESULTS:  50% (148/295) of participants in the intervention group responded to treatment compared with 43% (124/291) in the control group (adjusted odds ratio 1.3, 95% confidence interval 1.0 to 1.9; number needed to treat=13); a difference possibly due to chance (P=0.08). The intervention was associated with reductions in blood pressure (difference in mean systolic -2.7 mm Hg (95% confidence interval -4.7 to -0.6 mm Hg), mean diastolic -2.8 (-4.0 to -1.6 mm Hg); weight -1.0 kg (-1.8 to -0.3 kg), and body mass index -0.4 ( -0.6 to -0.1) but not cholesterol -0.1 (-0.2 to 0.0), smoking status (adjusted odds ratio 0.4, 0.2 to 1.0), or overall cardiovascular risk as a continuous measure (-0.4, -1.2 to 0.3)). The intervention was associated with improvements in diet, physical activity, drug adherence, and satisfaction with access to care, treatment received, and care coordination. One serious related adverse event occurred, when a participant was admitted to hospital with low blood pressure. CONCLUSIONS:  This evidence based telehealth approach was associated with small clinical benefits for a minority of people with high cardiovascular risk, and there was no overall improvement in average risk. The Healthlines service was, however, associated with improvements in some risk behaviours, and in perceptions of support and access to care.Trial registration Current Controlled Trials ISRCTN 27508731.

Social Support and Health in Diabetes Patients: An Observational Study in Six European Countries in an Era of Austerity.

INTRODUCTION: Support from individual social networks, community organizations and neighborhoods is associated with better self-management and health outcomes. This international study examined the relative impact of different types of support on health and health-related behaviors in patients with type 2 diabetes. METHODS: Observational study (using interviews and questionnaires) in a sample of 1,692 type 2 diabetes patients with 5,433 connections from Bulgaria, Greece, Netherlands, Norway, Spain, and the United Kingdom. Outcomes were patient-reported health status (SF-12), physical exercise (RAPA), diet and smoking (SDCSCA). Random coefficient regression models were used to examine linkages with individual networks, community organizations, and neighborhood type (deprived rural, deprived urban, or affluent urban). RESULTS: Patients had a median of 3 support connections and 34.6% participated in community organizations. Controlled for patients' age, sex, education, income and comorbidities, large emotional support networks were associated with decrease of non-smoking (OR = 0.87). Large practical support networks were associated with worse physical and mental health (B = -0.46 and -0.27 respectively) and less physical activity (OR = 0.90). Participation in community organizations was associated with better physical and mental health (B = 1.39 and 1.22, respectively) and, in patients with low income, with more physical activity (OR = 1.53). DISCUSSION: Participation in community organizations was most consistently related to better health status. Many diabetes patients have individual support networks, but this study did not provide evidence to increase their size as a public health strategy. The consistent association between participation in community organizations and health status provides a clear target for interventions and policies.

Voluntary Organizations and Community Groups as New Partners in Diabetes Self-management and Education: A Critical Interpretative Synthesis.

PURPOSE: The purpose of this study is to critically review the literature on the role and work of voluntary organizations and community groups and volunteers in diabetes self-management programs. It seeks to explain how these organizations are located and could be integrated further within a broader system of support. METHODS: A critical interpretative synthesis of the literature was undertaken as part of the conceptual development of a European research project. Evidence (2000-November 2014) was searched in databases, with the use of key terms, and limited to the languages of the participating countries. This was supplemented by an additional hand search and snowballing technique. A total of 21 articles were included in the review. RESULTS: Evidence regarding the involvement of voluntary organizations in diabetes self-management programs mainly related to: the nature and remit of their work, responsibilities, and attributes; key strategies of programs accounting for success; motivations/barriers for engaging in volunteering participation; relationships between volunteers and users; and connections/tensions with formal services. CONCLUSIONS: This review has uncovered a range of facets of voluntary organizations and community groups relevant for supporting diabetes self-management such as the context within which they act and the nature of relationships developed with community and health services. The principles of "assistance, support, sharing, and link" seem essential for this voluntary initiative in self-management to establish effective reciprocal collaboration with health professionals.

A novel function for UDP glycosyltransferase 8: galactosidation of bile acids.

The human UDP glycosyltransferase (UGT) superfamily comprises four families of enzymes that catalyze the addition of sugar residues to small lipophilic chemicals. The UGT1 and UGT2 enzymes use UDP-glucuronic acid, and UGT3 enzymes use UDP-N-acetylglucosamine, UDP-glucose, and UDP-xylose to conjugate xenobiotics, including drugs and endobiotics such as metabolic byproducts, hormones, and signaling molecules. This metabolism renders the substrate more polar and more readily excreted from the body and/or functionally inactive. The fourth UGT family, called UGT8, contains only one member that, unlike other UGTs, is considered biosynthetic. UGT8 uses UDP galactose to galactosidate ceramide, a key step in the synthesis of brain sphingolipids. To date other substrates for this UGT have not been identified and there has been no suggestion that UGT8 is involved in metabolism of endo- or xenobiotics. We re-examined the functions of UGT8 and discovered that it efficiently galactosidates bile acids and drug-like bile acid analogs. UGT8 conjugates bile acids ∼60-fold more efficiently than ceramide based on in vitro assays with substrate preference deoxycholic acid > chenodeoxycholic acid > cholic acid > hyodeoxycholic acid > ursodeoxycholic acid. Activities of human and mouse UGT8 are qualitatively similar. UGT8 is expressed at significant levels in kidney and gastrointestinal tract (intestine, colon) where conjugation of bile acids is likely to be metabolically significant. We also investigate the structural determinants of UDP-galactose selectivity. Our novel findings suggest a new role for UGT8 as a modulator of bile acid homeostasis and signaling.

Limiting radiation exposure during percutaneous nephrolithotomy.

BACKGROUND AND PURPOSE: An increase in the prevalence of urologic stone disease and the refinement of endourologic techniques has seen a concomitant rise in the use of fluoroscopy during surgery. As such, there has been increasing concern in regard to the intraoperative radiation exposure to both clinicians and patients. The objective of the study was to audit contemporary data on radiation exposure during percutaneous nephrolithotomy (PCNL), in comparison with published series, and demonstrate that relatively low levels are achievable with clinical vigilance and attention to technique Methods: A retrospective analysis was performed of all PCNLs undertaken between July 2005 and December 2011. The primary outcome measure was fluoroscopy times and associated radiation exposure, measured as dose area product (DAP). No statistical analysis was undertaken. RESULTS: Between July 2005 and October 2011, 376 PCNLs were performed. Data were available on 348 patients including 16 pediatric patients. Mean DAP and screening time (ST) over the whole study period were 45 cGy/cm(2) and 96s, respectively. On a year by year basis, the ST and DAP reduced from 917 to 375 and from 180 to 65, respectively. We acknowledge the limitation of this being a retrospective case series. CONCLUSIONS: This study represents the largest series to date on radiation exposure during PCNL and compares favorably with other published series, including those purporting novel techniques. Subtle changes in surgical technique and experience over time can lead to low screening times and can be potentially achieved by all operators performing PCNL within a high throughput center. It is now recognized that surgical outcome in stone surgery is related to caseload. The radiation dose the patient receives during PCNL is increasingly recognized to be an important factor and can be reduced by careful technique and experience.

Participation in voluntary and community organisations in the United Kingdom and the influences on the self-management of long-term conditions.

Voluntary and community organisations (VCOs) have health benefits for those who attend and are viewed as having the potential to support long-term condition management. However, existing community-level understandings of participation do not explain the involvement with VCOs at an individual level, or the nature of support, which may elicit health benefits. Framing active participation as 'doing and experiencing', the aim of this qualitative study was to explore why people with long-term vascular conditions join VCOs, maintain their membership and what prevents participation. Twenty participants, self-diagnosed as having diabetes, chronic heart disease or chronic kidney disease, were purposefully sampled and recruited from a range of VCOs in the North West of England identified from a mapping of local organisations. In semi-structured interviews, we explored the nature of their participation. Analysis was thematic and iterative involving a continual reflection on the data. People gave various reasons for joining groups. These included health and well-being, the need for social contact and pursuing a particular hobby. Barriers to participation included temporal and spatial barriers and those associated with group dynamics. Members maintained their membership on the basis of an identity and sense of belonging to the group, developing close relationships within it and the availability of support and trust. Participants joined community groups often in response to a health-related event. Our findings demonstrate the ways in which the social contact associated with continued participation in VCOs is seen as helping with long-term condition management. Interventions designed at improving chronic illness management might usefully consider the role of VCOs.

Connecting local support: A qualitative study exploring the role of voluntary organisations in long-term condition management.

OBJECTIVES: To examine the role of community groups to support people living with long-term conditions and the organisational factors that influence this role. METHODS: Thirty-three semi-structured interviews were conducted with voluntary group organisers purposefully sampled in Greater Manchester from a local database of community groups. Interviews explored the organisations role in supporting people living with a long-term condition, their social networks and the origins of the groups. RESULTS: Respondents' construed their role in supporting individual capacity for management either explicitly (e.g. providing exercise) or implicitly (e.g. emotional support). This role was influenced by a combination of group ideology, funding and social networks. Analysis highlights the role of the non-clinical setting, the social support provided within the group, as well as organisational processes that influenced their capacity to support people living with long-term conditions. CONCLUSION: By examining the organisation of voluntary groups, this study highlights the way in which they may support or constrain access to an extended range of support for people with long-term conditions. This paper has implications for commissioning of services by the health service from the third sector because of the differing ideological perspectives and limited operational capacity.

How potentially serious symptom changes are talked about and managed in COPD clinical review consultations: a micro-analysis.

People with Chronic Obstructive Pulmonary Disease (COPD) are at heightened risk of developing lung cancer. Recent research has suggested that in people who have the disease, the time between symptom onset and consultation can be long enough to significantly affect prognosis. The regular and routine clinical encounters that people with COPD engage in provide an opportunity for them to highlight new symptoms of concern, and for clinicians to be watchful for new symptomatic indicators. We present a micro-analysis of naturalistic data from a corpus of such encounters with the aim of exploring the interactional factors within these routine consultations which influence when and how new symptoms of concern are raised. Our hypothesis is that although the underlying aim of the review consultation is the same in both settings, the different consultation structures oriented to by nurses and GPs have a tangible effect on how new and concerning symptomatic information is introduced. Conversation analysis (CA) was used to examine 39 naturalistic review consultation recordings in two clinical settings; GP led (n = 16), and practice nurse led (n = 23). We describe three interactional formats by which patients chose to present new symptomatic concerns; 'direct', 'embedded', and 'oblique'. Both settings provided interactional 'slots' for patients to offer new and concerning symptomatic information. However, the structure of nurse led encounters tended to limit opportunities for patients to develop extended symptom narratives which in turn facilitated 'oblique' formats. We suggest that the attenuation of the 'oblique' format in this particular clinical setting has implications relating to the psycho-social idiosyncrasies of lung cancer and the maintenance of interactional conditions that encourage patients to disclose new symptomatic concerns.

Epirubicin upregulates UDP glucuronosyltransferase 2B7 expression in liver cancer cells via the p53 pathway.

Anthracyclines are effective genotoxic anticancer drugs for treating human malignancies; however, their clinical use is limited by tumor resistance and severe cardiotoxicity (e.g., congestive heart failure). Epirubicin (EPI) is less cardiotoxic compared with other canonical anthracyclines (e.g., doxorubicin). This has been attributed to its unique glucuronidation detoxification pathway. EPI is primarily inactivated by UDP-glucuronosyltransferase 2B7 (UGT2B7) in the liver. Hence, the regulation of hepatic UGT2B7 expression is critical for EPI systemic clearance but remains poorly characterized. We show herein that EPI upregulates UGT2B7 expression in hepatocellular carcinoma (HCC) HepG2 and Huh7 cells. Our analyses of deleted and mutated UGT2B7 promoter constructs identified a p53 response element (p53RE) in the UGT2B7 promoter. EPI stimulated UGT2B7 promoter activity via this p53RE and enhanced in vivo p53 binding at this p53RE in HepG2 cells. Knockdown of p53 expression by small interfering RNA silencing technology significantly repressed the capacity of EPI to stimulate UGT2B7 transcription. Furthermore, the p53 activator nutlin-3α significantly enhanced UGT2B7 expression and recruited the p53 protein to the UGT2B7 p53RE in HepG2 cells. Collectively, our results demonstrated that EPI promotes its own detoxification via the p53-mediated pathway. This regulation may contribute to tumor resistance to EPI-containing HCC chemotherapy and may also provide a new explanation for the reduced cardiotoxicity of EPI compared with other anthracyclines. Our finding also suggests that upon exposure to genotoxic agents, detoxifying genes are activated by the p53-mediated pathway to clear genotoxic agents locally within the tumor site or even systemically through the liver.

Free and total plasma cortisol measured by immunoassay and mass spectrometry following ACTH1₋24 stimulation in the assessment of pituitary patients.

CONTEXT: Measurement of plasma cortisol by immunoassay after ACTH1₋24 stimulation is used to assess the hypothalamic-pituitary-adrenal (HPA) axis. Liquid chromatography-tandem mass spectrometry (LCMS) has greater analytical specificity than immunoassay and equilibrium dialysis allows measurement of free plasma cortisol. OBJECTIVE: We investigated the use of measuring total and free plasma cortisol by LCMS and total cortisol by immunoassay during an ACTH1₋24 stimulation test to define HPA status in pituitary patients. DESIGN AND SETTING: This was a case control study conducted in a clinical research facility. PARTICIPANTS: We studied 60 controls and 21 patients with pituitary disease in whom HPA sufficiency (n = 8) or deficiency (n = 13) had been previously defined. INTERVENTION: Participants underwent 1 µg ACTH(1-24) intravenous and 250 µg ACTH1₋24 intramuscular ACTH1₋24 stimulation tests. MAIN OUTCOME MEASURES: Concordance of ACTH1₋24-stimulated total and free plasma cortisol with previous HPA assessment. RESULTS: Total cortisol was 12% lower when measured by immunoassay than by LCMS. Female sex and older age were positively correlated with ACTH1₋24-stimulated total and free cortisol, respectively. Measurements of total cortisol by immunoassay and LCMS and free cortisol 30 minutes after 1 µg and 30 and 60 minutes after 250 µg ACTH1₋24 were concordant with previous HPA axis assessment in most pituitary patients. However, free cortisol had greater separation from the diagnostic cutoff than total cortisol. CONCLUSIONS: Categorization of HPA status by immunoassay and LCMS after ACTH1₋24 stimulation was concordant with previous assessment in most pituitary patients. Free cortisol may have greater clinical use in patients near the diagnostic threshold.

Access to mental health in primary care: a qualitative meta-synthesis of evidence from the experience of people from 'hard to reach' groups.

Knowledge about depression, access and help-seeking has increasingly been influenced from a range of disciplines including clinical and applied social science. A range of interventions can improve outcomes of depression and anxiety. However, many in need do not seek help, or their interaction with care-givers does not address their needs. We carried out a systematic search for qualitative articles focusing on the experiences of eight exemplar groups with exceptional problems in access (the homeless, long-term unemployed, adolescents with eating disorders, depressed elderly people, advanced cancer sufferers, patients with medically unexplained symptoms, asylum seekers and people from black and minority ethnic groups). Twenty articles representing these groups were selected, findings were then developed using qualitative meta-synthesis, this suggested a range of mechanisms accounting for poor access among these groups. Many regarded their mental health problems as rooted in social problems and employed a variety of self-management strategies to maintain function. These strategies could involve social withdrawal, focusing available resources on close family relationships and work roles. Over-investment in these roles could result in a sense of insecurity as wider networks were neglected. Material disadvantage affected both the resources people could bring to performing social roles and influenced help-seeking. A tacit understanding of the material, psychological and social 'costs' of engagement by patients and health professionals could influence decisions to seek and offer help. These costs were felt to be proportionally higher in deprived, marginalized and minority communities, where individual resources are limited and the stigma attached to mental ill-health is high.

Lateral violence in the perioperative setting.

Lateral violence is disruptive, bullying, intimidating, or unsettling behavior that occurs between nurses in the workplace. The perioperative setting fosters lateral violence because of the inherent stress of performing surgery; high patient acuity; a shortage of experienced personnel; work demands; and the restriction and isolation of the OR, which allows negative behaviors to be concealed more easily. Lateral violence affects nurses' health and well-being and their ability to care for patients. Interventions to reduce lateral violence include empowerment of staff members and zero tolerance for lateral violence.

Recommendation for and receipt of cancer screenings among medicaid recipients 50 years and older.

BACKGROUND: Persons of low socioeconomic status, including those with Medicaid coverage, are more likely to be diagnosed with cancer at an advanced stage, but little is known about cancer screening practices among Medicaid recipients. Our objective was to identify cancer screening rates among older Medicaid recipients seen in a primary care setting, and to identify patient and physician characteristics associated with screening. METHODS: We used a stratified cluster sampling design to select a representative sample of 1951 North Carolina Medicaid recipients 50 years and older. Medical records were reviewed in the office of the primary care provider. Principal outcomes were the documentation of physician recommendations for and patient receipt of screening examinations for colorectal, breast, and cervical cancer. RESULTS: Documentation that colorectal, breast, and cervical cancer screening was recommended by the primary care provider was found for only 52.7%, 60.4%, and 51.5% of eligible patients, respectively. Documented rates of adequate screening were 28.2% for colorectal cancer, 31.7% for mammography within 2 years, and 31.6% for Papanicolaou test within 3 years. When medical record and claims data were combined, approximately half of eligible patients had evidence of screening. Length of the patient-physician relationship and African American race were positively associated with screening. CONCLUSIONS: Cancer screening rates among older Medicaid recipients fall far short of national objectives. Lack of a screening recommendation by the physician, rather than patient refusal of recommended tests, accounted for most instances of screening delinquency. Efforts to increase cancer screening rates among Medicaid recipients must address patient, physician, and organizational barriers to the routine identification and delivery of preventive services.

Informed consent? How do primary care professionals prepare women for cervical smears: a qualitative study.

BACKGROUND: Cervical screening is a procedure that is mainly carried out in primary care, predominantly by general practitioners (GPs) and practice nurses (PNs). Much has been published about the effects on women of receiving an abnormal smear result but little has been done to investigate the preparation of women by primary care professionals for this. OBJECTIVE: To explore the self-reported behaviours of GPs and PNs in preparing a woman for a cervical smear test and possible abnormal result. METHODS: Letters inviting respondents to participate were sent to selected GPs and PNs at medical student teaching practices in Manchester, England. Twelve GPs and 15 PNs were interviewed. Interviews were audiotaped and covered aspects of the cervical screening programme, practice protocols and explored views about consenting a woman for a smear test and the information giving about the possibility of an abnormal test result. Interviews were analysed by constant comparison and the interview schedule modified. Recruitment for interviews ceased when category saturation was achieved. CONCLUSION: PNs and GPs differed widely in their descriptions of how they prepare a women for a smear. PNs reported following routines which they felt incorporated women's questions and anxieties; GPs reported that the discussion with the woman depended on the reason for doing the smear but also the amount of time available within the consultation. Few respondents reported raising issues of reliability or sensitivity of the test with women, neither did they report discussing with women the possibility of an abnormal smear result or what further investigation and treatment may be required. The degree of persuasion reported by practitioners used to encourage women to attend for smears varied and was related to their attitudes to the national cervical screening programme. PRACTICE IMPLICATIONS: The current system for recall being separate from practice activity, whilst ensuring accuracy of the data-base, may limit the opportunity for information-giving which is sensitive to the needs to the local population. There is a need to include consent issues in the training of PNs, rather than just practical aspects of smear-taking, and to formalise training updates for GPs. In addition, the taking of opportunistic smears and the constraints placed upon time and information-giving need addressing. The role of other primary care staff in encouraging women to attend for smears raises training needs for these staff which practices or primary care trusts must address.

Attempted control of hyperglycemia during cardiopulmonary bypass fails to improve neurologic or neurobehavioral outcomes in patients without diabetes mellitus undergoing coronary artery bypass grafting.

OBJECTIVE: Hyperglycemia worsens outcomes in critical illness. This randomized, double-blind, placebo-controlled clinical trial tested whether insulin treatment of hyperglycemia during cardiopulmonary bypass would reduce neurologic, neuro-ophthalmologic, and neurobehavioral outcomes after coronary artery bypass grafting. METHODS: Three hundred eighty-one nondiabetic patients undergoing isolated coronary artery bypass grafting were given infusions of insulin or placebo when their blood glucose concentration exceeded 100 mg/dL during cardiopulmonary bypass. The primary outcome measure was the combined incidence of new neurologic, neuro-ophthalmologic, or neurobehavioral deficits or neurologic death observed at 4 to 8 days postoperatively. This same measure was assessed secondarily at 6 weeks and 6 months. Length of hospital stay was also compared as a secondary assessment. RESULTS: The 2 groups were well matched at baseline. The insulin-treated group had significantly lower blood glucose concentrations during bypass. Sixty-six percent of subjects in the insulin-treated group and 67% of subjects in the control group demonstrated a new or worsening neurologic, neuro-ophthalmologic, or neurobehavioral deficit or neurologic death at the 4- to 8-day assessment. Outcomes were also similar in the 2 groups at 6 weeks (37% and 39% incidence, respectively) and 6 months (30% and 25%, respectively). Median lengths of stay were 7 and 6 days, respectively, in the treatment and control groups. None of these outcome differences was statistically significant. CONCLUSION: Attempted control of hyperglycemia during cardiopulmonary bypass had no significant effect on the combined incidence of neurologic, neuro-ophthalmologic, or neurobehavioral deficits or neurologic death and failed to shorten the length of hospital stay. These results do not contradict those of other studies showing that aggressive control of hyperglycemia in the postoperative period will improve outcome.

User involvement in clinical governance.

OBJECTIVES: To investigate the involvement of users in clinical governance activities within Primary Care Groups (PCGs) and Trusts (PCTs). Drawing on policy and guidance published since 1997, the paper sets out a framework for how users are involved in this agenda, evaluates practice against this standard and suggests why current practice for user involvement in clinical governance is flawed and why this reflects a flaw in the policy design as much as its implementation. DESIGN: Qualitative data comprising semi-structured interviews, reviews of documentary evidence and relevant literature. SETTING: Twelve PCGs/PCTs in England purposively selected to provide variation in size, rurality and group or trust status. PARTICIPANTS: Key stakeholders including Lay Board members (n = 12), Chief Executives (CEs) (n = 12), Clinical Governance Leads (CG leads) (n = 14), Mental Health Leads (MH leads) (n = 9), Board Chairs (n = 2) and one Executive Committee Lead. RESULTS: Despite an acknowledgement of an organizational commitment to lay involvement, in practice very little has occurred. The role of lay Board members in setting priorities and implementing and monitoring clinical governance remains low. Beyond Board level, involvement of users, patients of GP practices and the general public is patchy and superficial. The PCGs/PCTs continue to rely heavily on Community Health Councils (CHCs) as a conduit or substitute for user involvement; although their abolition is planned, their role to be fulfilled by new organizations called Voices, which will have an expanded remit in addition to replacing CHCs. CONCLUSIONS: Clarity is required about the role of lay members in the committees and subcommittees of PCGs and PCTs. Involvement of the wider public should spring naturally from the questions under consideration, rather than be regarded as an end in itself.

Intraoperative insulin therapy does not reduce the need for inotropic or antiarrhythmic therapy after cardiopulmonary bypass.

OBJECTIVE: To determine whether attempted glucose control through intraoperative insulin therapy reduces the need for inotropic or antiarrhythmic therapy after cardiopulmonary bypass (CPB). DESIGN: Post hoc analysis of a randomized, masked clinical trial of insulin therapy for prevention of neurobehavioral deficits. SETTING: Single university hospital. PARTICIPANTS: Nondiabetic patients undergoing elective coronary artery bypass graft surgery (n = 381). INTERVENTIONS: Patients received either insulin infusions in an attempt to maintain blood glucose at 80 to 120 mg/dL (n = 188) or placebo (saline; n = 193). Inotropic therapy was defined as the initiation of vasoactive support with epinephrine or amrinone infusions or mechanical support with the initiation of an intra-aortic balloon pump in the operating room or within 12 hours postoperatively. Antiarrhythmic therapy was defined as cardioversion, antiarrhythmic medications, or pacing. MEASUREMENTS AND MAIN RESULTS: Of patients, 64 in the placebo group and 71 in the insulin group required inotropic support after CPB (p = not significant). The use of cardioversion (55 in placebo group v 61 in insulin group), antiarrhythmic medications (64 in placebo group v 76 in insulin group), and pacing (118 in placebo group v 117 in insulin group) was similar between groups. Inotropic drug support was associated with age >60 years, female gender, reduced preoperative ejection fraction, history of angina, and increased duration of CPB. CONCLUSION: Intraoperative insulin therapy did not reduce the use of inotropic or antiarrhythmic support after cardiac surgery with CPB. The lack of benefit may be due to the inability to prevent hyperglycemia during the physiologic stress of CPB or a tribute to the effectiveness of modern myocardial preservation techniques.

Emboli and Neuropsychological Outcome Following Cardiopulmonary Bypass.

The dramatic decline in mortality related to cardiac surgery has resulted in over 330,000 surgeries involving cardiopulmonary bypass (CPB) being performed yearly in the United States. Although few patients die as a result of cardiac surgery, over two thirds of the patients demonstrate evidence of acute neuropsychological dysfunction postoperatively. The potential mechanisms contributing to post-CPB neuropsychological deficits are many, but two major inter-related etiologic factors, hypo-perfusion and emboli, are suggested as the probable culprits. If embolism is the cause of the deficits, increasing cerebral perfusion would deliver more emboli and increase the amount and severity of injury. Conversely, if hypoperfusion is the cause of the injury, then decreasing brain blood flow to minimize embolic delivery would increase the likelihood of perfusion injury. By monitoring the carotid arteries of patients undergoing coronary artery bypass graft surgery, we have determined the frequency and quantity of embolic signals that occur during CPB. Although we have not been able to determine the nature of the embolus, gaseous or solid, we have demonstrated a relationship between the overall embolic load and the probability of having NP dysfunction. (ECHOCARDIOGRAPHY, Volume 13, September 1996)