Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study

BACKGROUND: Head-to-head comparisons of combinations of more than one non-opioid analgesic (NOA) with morphine alone, for postoperative analgesia, are lacking. The objective of this multicentre, randomised, double-blind controlled trial was to compare the morphine-sparing effects of different combinations of three NOAs-paracetamol (P), nefopam (N), and ketoprofen (K)-for postoperative analgesia. METHODS: Patients from 10 hospitals were randomised to one of eight groups: control (C) received saline as placebo, P, N, K, PN, PK, NK, and PNK. Treatments were given intravenously four times a day during the first 48 h after surgery, and morphine patient-controlled analgesia was used as rescue analgesia. The outcome measures were morphine consumption, pain scores, and morphine-related side-effects evaluated 24 and 48 h after surgery. RESULTS: Two hundred and thirty-seven patients undergoing a major surgical procedure were included between July 2013 and November 2016. Despite a failure to reach a calculated sample size, 24 h morphine consumption [median (inter-quartile range)] was significantly reduced in the PNK group [5 (1-11) mg] compared with either the C group [27 (11-42) mg; P<0.05] or the N group [21 (12-29) mg; P<0.05]. Results were similar 48 h after surgery. Patients experienced less pain in the PNK group compared with the C, N, and P groups. No difference was observed in the incidence of morphine-related side-effects. CONCLUSIONS: Combining three NOAs with morphine allows a significant morphine sparing for 48 h after surgery associated with superior analgesia the first 24 h when compared with morphine alone. CLINICAL TRIAL REGISTRATION: EudraCT: 2012-004219-30; NCT01882530

The sense of smell, its signalling pathways, and the dichotomy of cilia and microvilli in olfactory sensory cells

Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the significance of olfaction to human life and speculate on what evolutionary factors contribute to keeping it alive. We then outline the functional architecture of olfactory sensory neurons and their signal transduction pathways, which are the primary detectors that render olfactory perception possible. Throughout the phylogenetic tree, olfactory neurons, at their apical tip, are either decorated with cilia or with microvilli. The significance of this dichotomy is unknown. It is generally assumed that mammalian olfactory neurons are of the ciliary type only. The existance of so-called olfactory microvillar cells in mammals, however, is well documented, but their nature remains unclear and their function orphaned. This paper discusses the possibility, that in the main olfactory epithelium of mammals ciliated and microvillar sensory cells exist concurrently. We review evidence related to this hypothesis and ask, what function olfactory microvillar cells might have and what signalling mechanisms they use

Encyclopedia of Questions and Answers: Over 800 Illustrations And Photographs

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P1462IMPACT OF HEART RATE AND BETA-BLOCKER USE ON THE LONG-TERM SURVIVAL OF CHRONIC HEMODIALYSIS PATIENTS

Abstract Background and Aims Increase in resting heart rate might influence mortalities of dialysis patients, and the use of β-blocker might improve their survival probability. However, the influence of heart rate and benefits of β-blocker on their survival are difficult to quantify because of following obstacles: prone to measurement errors; inherent association of heart rate with blood pressures, comorbidities, and medication use; and a necessity of repeated measurements of vital signs and medication use. Therefore, at the design process of our previous randomized control trial on the Olmesartan Clinical Trial in Okinawan patients under OKIDS (OCTOPUS), we included the repeated measures design to quantify the influence of vital sign values on the survival retrospectively. We combined the repeated measurement data and additional the long-term prognosis information of the participants obtained after the OCTOPUS with aim of investigating the influence of time varying covariates: heart rates, blood pressures, and β-blocker use, on the long-term survival of hemodialysis patients. Method We investigated 461 adult OCTOPUS participants who received chronic hemodialysis and antihypertensive medications in Okinawa. The OCTOPUS trial, which was conducted between June 2006 and June 2011, did not detect the survival benefit of angiotensin receptor blocker (ARB)NDT 2013, but the study and the additional follow-up of participants’ prognosis provided us with information to investigate influence of predictors on long-term survival in the population. Throughout the OCTOPUS trial, study participants were measured pre-dialysis blood pressures, pre-dialysis resting heart rates, and their medication use for one week at their dialysis centers every six months after their participations. Following the trial, we collected the prognosis information of all participants until July 31st, 2018. Finally, we merged the multiple-measured data during the OCTOPUS with the prognosis data. Mean values of three measurements of blood pressures and heart rates and β-blocker use were introduced to the Cox-regression model as time-varying covariates with essential non-time varying covariates, which include age, gender, and diabetes. Results In this retrospective cohort study, 221 (47.9%) out of 461 participants deceased, and the median follow-up length was 10.21 years. Initial mean resting heart rate and pre-dialysis mean blood pressure were 78(±10) per minute and 159.5(±14) mmHg, respectively. 10% of participants were prescribed β-blocker initially. The resting heart rate of all participants significantly decreased by 1.75 and 2.45 per minutes after two and four years respectively. β-blocker could significantly decrease the mean heart rate by 3.54 and 2.90 per minutes after two and four years. With our Cox-regression with the time varying covariates, increase of heart rate was significantly associated with higher mortality (P=0.002), but the use of β-blocker was not associated with the mortality. (P=0.691) Additionally, we could not detect the interaction of heart rate and β-blocker use on the mortality. (P= 0.796) Although lower blood pressure was significantly associated with higher mortality in our initial Cox-regression analysis, an introduction of interaction term of heart rate and blood pressure remove the significance of influence of blood pressure on the survival. Conclusion In hypertensive chronic hemodialysis patients, higher heart rate is associated with higher mortality. However, use of beta-blocker was not associated with improvement of their mortality. </jats:sec

Optimising cardiac surgery outcomes in people with diabetes: the OCTOPuS pilot feasibility study

Background: surgical outcomes are worse in people with diabetes, in part, because of the effects of hyperglycaemia, obesity and other comorbidities. Two important uncertainties in the management of people with diabetes undergoing major surgery exist: (1) how to improve diabetes management prior to an elective procedure and (2) whether that improved management leads to better post-operative outcomes. Objective: the Optimising Cardiac Surgery ouTcOmes in People with diabeteS project aimed to assess whether a pre-operative outpatient intervention delivered by a multidisciplinary specialist diabetes team could improve diabetes management and cardiac surgical outcomes for people with diabetes. Although the intervention could be applied to any surgical discipline, cardiothoracic surgery was chosen because 30–40% of those undergoing elective cardiac revascularisation have diabetes.Methods: the project had three phases: (1) designing the intervention, (2) a pilot study of the intervention and (3) a multicentre randomised controlled study in United Kingdom cardiothoracic centres to assess whether the intervention could improve surgical outcomes. The first two phases were completed, but the COVID-19 pandemic and its subsequent effects on cardiothoracic services and research capacity in the United Kingdom meant that the randomised controlled study could not be undertaken. Intervention development: two rapid literature reviews were undertaken to understand what factors influence surgical outcomes in people with diabetes and what interventions have previously been tested. The Optimising Cardiac Surgery ouTcOmes in People with diabeteS intervention was based on an existing nurse-led outpatient intervention, delivered in the 3 months before elective orthopaedic surgery. This intervention reduced pre-operative glycated haemoglobin and reduced length of stay. We undertook a survey of United Kingdom cardiothoracic surgeons, which found limited and inconsistent pre-operative management of people with diabetes awaiting cardiothoracic surgery. A prototype intervention was developed following discussions with relevant stakeholders. Pilot study: the pilot feasibility study recruited 17 people with diabetes and was undertaken by the diabetes and cardiothoracic surgery departments at University Hospital Southampton NHS Foundation Trust. Biomedical data were collected at baseline and prior to surgery. We assessed how the intervention was used. In-depth qualitative interviews with participants and healthcare professionals explored perceptions and experiences of the intervention and how it might be improved. Thirteen people completed the study and underwent cardiothoracic surgery. All components of the Optimising Cardiac Surgery ouTcOmes in People with diabeteS intervention were used, but not all parts were used for all participants. Minor changes were made to the intervention following feedback from the participants and healthcare professionals. Median (interquartile range) glycated haemoglobin fell 10 mmol/mol (3–13) prior to surgery. The median duration of admission for surgery was 7 (interquartile range 6–9) days. Multicentre randomised controlled study of the United Kingdom cardiothoracic centres: we could not proceed to the multicentre randomised controlled study because of the impact of COVID-19 on the delivery of cardiothoracic surgical services and research capacity. Conclusion: there remains an urgent need to improve the surgical outcomes for people with diabetes. This project demonstrated that it is possible to develop a clinical pathway to improve diabetes management prior to admission. Limitations: we could not test the effectiveness of the intervention in a multicentre randomised controlled trial because of the COVID-19 pandemic. Future work: the intervention is available for future research or clinical implementation.</p