Pre‐emptive and preventive opioids for postoperative pain in adults undergoing all types of surgery

Background: Postoperative pain is a common consequence of surgery and can have deleterious effects. It has been suggested that the administration of opioid analgesia before a painful stimulus may improve pain control. This can be done in two ways. We defined 'preventive opioids' as opioids administered before incision and continued postoperatively, and 'pre‐emptive opioids' as opioids given before incision but not continued postoperatively. Both pre‐emptive and preventive analgesia involve the initiation of an analgesic agent prior to surgical incision with the aim of reducing intraoperative nociception and therefore postoperative pain.Objectives: To assess the efficacy of preventive and pre‐emptive opioids for reducing postoperative pain in adults undergoing all types of surgery.Search methods: We searched the following electronic databases: CENTRAL, MEDLINE, Embase, AMED, and CINAHL (up to 18 March 2018). In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles. We did not apply any restrictions on language or date of publication.Selection criteria: We included parallel‐group randomized controlled trials (RCTs) only. We included participants aged over 15 years old undergoing any type of surgery. We defined postincision opioids as the same intervention administered after incision whether single dose (as comparator with pre‐emptive analgesia) or continued postoperatively (as comparator with preventive analgesia) (control group). We considered studies that did and did not use a double‐dummy placebo (e.g. intervention group received active drug before incision and placebo after incision; control group received placebo before incision and active drug after incision).Data collection and analysis: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: early acute postoperative pain (measured within six hours and reported on a 0‐to‐10 scale) and respiratory depression. Our secondary outcomes included: late acute postoperative pain (24 to 48 hours and reported on a 0‐to‐10 scale), 24‐hour morphine consumption, and adverse events (intraoperative bradycardia and hypotension). We used GRADE to assess the quality of the evidence for each outcome.Main results: We included 20 RCTs, including one unpublished study with 1343 participants. Two studies were awaiting classification as the full text for these studies was not available. One study evaluated pre‐emptive opioids, and 19 studies evaluated preventive opioids. We considered only one study to be at low risk of bias for most domains. The surgeries and opioids used varied, although roughly half of the included studies were conducted in abdominal hysterectomy, and around a quarter used morphine as the intervention. All studies were conducted in secondary care.Pre‐emptive opioids compared to postincision opioidsFor pre‐emptive opioids in dental surgery, there may be a reduction in early acute postoperative pain (mean difference (MD) ‐1.20, 95% confidence interval (CI) ‐1.75 to ‐0.65; 40 participants; 1 study; low‐quality evidence). This study did not report on adverse events (respiratory depression, bradycardia, or hypotension). There may be a reduction in late acute postoperative pain (MD ‐2.10, 95% CI ‐2.57 to ‐1.63; 40 participants; 1 study; low‐quality evidence). This study did not report 24‐hour morphine consumption.Preventive opioids compared to postincision opioidsFor preventive opioids, there was probably no reduction in early acute postoperative pain (MD 0.11, 95% CI ‐0.32 to 0.53; 706 participants; 10 studies; I2 = 61%; moderate‐quality evidence). There were no events of respiratory depression in four studies (433 participants). There was no important reduction in late acute postoperative pain (MD ‐0.06, 95% CI ‐0.13 to 0.01; 668 participants; 9 studies; I2 = 0%; moderate‐quality evidence). There may be a small reduction in 24‐hour morphine consumption (MD ‐4.91 mg, 95% CI ‐9.39 mg to ‐0.44 mg; 526 participants; 11 studies; I2 = 82%; very low‐quality evidence). There may be similar rates of bradycardia (risk ratio (RR) 0.33, 95% CI 0.01 to 7.88; 112 participants; 2 studies; I2 = 0%; low‐quality evidence) and hypotension (RR 1.08, 95% CI 0.25 to 4.73; 88 participants; 2 studies; I2 = 0%; low‐quality evidence).Authors' conclusions: Due to the low quality of the evidence, we are uncertain whether pre‐emptive opioids reduce postoperative pain. Based on the trials conducted thus far, there was no clear evidence that preventive opioids result in reductions in pain scores. It was unclear if there was a reduction in morphine consumption due to very low‐quality of evidence. Too few studies reported adverse events to be able to draw any definitive conclusions. Once assessed, the two studies awaiting classification may alter the conclusions of the review

Isolation, structure elucidation, identification and quantitative analysis of di(2-ethylhexyl) phthalate (DEHP) from the roots of Chlorophytum boriviliuanum (safed musli)

Chlorophytum borivilianum (safed musli) is a traditional herbaceous medicinal plant belonging to family Liliaceae. Its roots are being employed in folk medicine. The crude extract of C. borivilianum has been consumed due to its versatile therapeutic uses. The scientific studies related to the important pharmacological properties are widely conducted and the remarkable bioactivities of C. borivilianum are proven in literatures. So far, the isolated chemical compounds are mainly saponins. In this research, the isolation was focused on compounds other than saponins and bis(2-ethylhexyl) benzene-1,2-dicarboxylate was isolated for the first time from the roots of C. borivilianum. The structure was identified based on the spectral data of 1H NMR, 13C NMR, DEPT, COSY, HMBC, HMQC and also based on the comparison with the previous literature data. This is the first report regarding the presence of this compound in C. borivilianum as well as its genus. A high performance liquid chromatographic (HPLC) method with photodiode array detection was established to identify and quantify bis(2-ethylhexyl) benzene-1,2-dicarboxylate

Self-help materials for the prevention of smoking relapse: study protocol for a randomized controlled trial.

BACKGROUND: Most people who stop smoking successfully for a few weeks will return to smoking again in the medium term. There are few effective interventions to prevent this relapse and none used routinely in clinical practice. A previous exploratory meta-analysis suggested that self-help booklets may be effective but requires confirmation. This trial aims to evaluate the effectiveness and cost-effectiveness of a set of self-help educational materials to prevent smoking relapse in the National Health Service (NHS) Stop Smoking Service. METHODS/DESIGN: This is an open, randomized controlled trial. The target population is carbon monoxide (CO) verified quitters at four weeks in the NHS stop smoking clinic (total sample size N = 1,400). The experimental intervention tested is a set of eight revised Forever Free booklets, including an introduction booklet and more extensive information on all important issues for relapse prevention. The control intervention is a leaflet that has no evidence to suggest it is effective but is currently given to some patients using NHS stop smoking services. Two follow-up telephone interviews will be conducted at three and 12 months after the quit date. The primary outcome will be prolonged abstinence from months four to 12 with no more than five lapses, confirmed by a CO test at the 12-month assessment. The secondary outcomes will be seven-day self-report point prevalence abstinence at three months and seven-day biochemically confirmed point prevalence abstinence at 12 months. To assess cost-effectiveness, costs will be estimated from a health service perspective and the EQ-5D will be used to estimate the QALY (Quality Adjusted Life Year) gain associated with each intervention. The comparison of smoking abstinence rates (and any other binary outcomes) between the two trial arms will be carried out using odds ratio as the outcome statistic and other related statistical tests. Exploratory subgroup analyses, including logistic regression analyses with interaction terms, will be conducted to investigate possible effect-modifying variables. DISCUSSION: The possible effect of self-help educational materials for the prevention of smoking relapse has important public health implications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN36980856.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Sticking under wet conditions: the remarkable attachment abilities of the torrent frog, staurois guttatus

Tree frogs climb smooth surfaces utilising capillary forces arising from an air-fluid interface around their toe pads, whereas torrent frogs are able to climb in wet environments near waterfalls where the integrity of the meniscus is at risk. This study compares the adhesive capabilities of a torrent frog to a tree frog, investigating possible adaptations for adhesion under wet conditions. We challenged both frog species to cling to a platform which could be tilted from the horizontal to an upside-down orientation, testing the frogs on different levels of roughness and water flow. On dry, smooth surfaces, both frog species stayed attached to overhanging slopes equally well. In contrast, under both low and high flow rate conditions, the torrent frogs performed significantly better, even adhering under conditions where their toe pads were submerged in water, abolishing the meniscus that underlies capillarity. Using a transparent platform where areas of contact are illuminated, we measured the contact area of frogs during platform rotation under dry conditions. Both frog species not only used the contact area of their pads to adhere, but also large parts of their belly and thigh skin. In the tree frogs, the belly and thighs often detached on steeper slopes, whereas the torrent frogs increased the use of these areas as the slope angle increased. Probing small areas of the different skin parts with a force transducer revealed that forces declined significantly in wet conditions, with only minor differences between the frog species. The superior abilities of the torrent frogs were thus due to the large contact area they used on steep, overhanging surfaces. SEM images revealed slightly elongated cells in the periphery of the toe pads in the torrent frogs, with straightened channels in between them which could facilitate drainage of excess fluid underneath the pad

PID tuning with input constraint: application on food processing

PID controllers are probably the most common used industrial controller. PID controller has gone through few decades and has survived successfully through the changes of technology from analogue era into digital era. Actuator saturation is among the most common and significant problem in control systems design as it may lead to instability and consequently affect the performance of the process. Normal PID controller does not take this into consideration. Normally, an anti windup compensator is added as the remedy for this constraint. For alternative, this research investigates the possibility to tune PI controller when the system is under saturation. This research will put emphasis on first order plus time delay process and an expression is developed for saturation level, U as a function of controller gain, c K with the range of R 0.8-2 (ratio of time delay to time constant). Simple and accurate correlations are obtained for the saturation level (u) and controller gain, Kc. The proposed relations overcome this input constraint by explicitly considering the saturation level during the tuning of PI controller. Thus, saturation can be avoided and at the same time, it gives satisfactory performance. This method is named as BL tuning method and applied on spray drying process. The results showed that this BL tuning method could give satisfactory performance in controlling the process

Design of PI controller with input constraint: application on blending process

Because of their simplicity, reliability and effectiveness, proportional–integral–derivative (PID) controllers remain the most widely used controllers in the process industries. Actuator saturation is among the most common and significant problem in control systems design. Normal PID controller does not take this into consideration. Normally, an anti‐windup compensator is employed in the system to overcome the problem. In this contribution, a new set of controller tuning relations is developed to tune the PI controller when the system is under saturation. The blending process was described as first order plus time delay (FOPTD) process and an expression is developed for saturation level, U as a function of controller gain, Kc with the range of R 0.4–2 (ratio of time delay to time constant). The proposed tuning rule relate the parameters of the controller to the parameters of a FOPTD model of the plant to a step change in the set point. The proposed method was applied to PI controller and tested on the process of blending system of sweetened condensed milk. The performance of the controller with various tuning formulae incorporated with classical anti‐windup strategies has been compared. The simulation results showed that the proposed method could give satisfactory performance in controlling the process

Repression of cyclin D1 as a target for germ cell tumors

Metastatic germ cell tumors (GCT) are curable, however GCTs refractory to cisplatin-based chemotherapy have a poor prognosis. This study explores D-type cyclins as molecular targets in GCTs because all-trans-retinoic acid (RA)-mediated differentiation of the human embryonal carcinoma (EC) cell line NT2/D1 is associated with G1 cell cycle arrest and proteasomal degradation of cyclin D1. RA effects on D-type cyclins are compared in human EC cells that are RA sensitive or dually RA and cisplatin resistant (NT2/D1-R1) and in clinical GCTs that have both EC and mature teratoma components. Notably, GCT differentiation was associated with reduced cyclin D1 but increased cyclin D3 expression. RA was shown here to repress cyclin D1 through a transcriptional mechanism in addition to causing its degradation. The siRNA-mediated repression of individual cyclin D species resulted in growth inhibition in both RA sensitive and resistant EC cells. Only repression of cyclin D1 occurred in vitro and when clinical GCTs mature, implicating cyclin D1 as a molecular therapeutic target. To confirm this, the EGFR-tyrosine kinase inhibitor, Erlotinib, was used to repress cyclin D1. This inhibited proliferation in RA and cisplatin sensitive and resistant EC cells. Taken together, these findings implicate cyclin D1 targeting agents for the treatment of GCTs

Self-help educational booklets for the prevention of smoking relapse following smoking cessation treatment: a randomized controlled trial.

AIMS: Most people who quit smoking for a short term will return to smoking again in 12 months. We tested whether self-help booklets can reduce relapse in short-term quitters after receiving behavioural and pharmacological cessation treatment. DESIGN: A parallel-arm, pragmatic individually randomized controlled trial. SETTING: Smoking cessation clinics in England. Participants People who stopped smoking for 4 weeks after receiving cessation treatment in stop smoking clinics. INTERVENTION: Participants in the experimental group (n=703) were mailed eight booklets, each of which taught readers how to resist urges to smoke. Participants in the control group (n=704) received a leaflet currently used in practice. MEASUREMENTS: The primary outcome was prolonged, carbon monoxide-verified abstinence from months 4 to 12. The secondary outcomes included 7-day self-reported abstinence at 3 and 12 months. Mixed-effects logistic regression was used to estimate treatment effects and to investigate possible effect modifying variables. FINDINGS: There were no statistically significant differences between the groups in prolonged abstinence from months 4 to 12 (36.9% versus 38.6%; odds ratio 0.93, 95% confidence interval 0.75-1.16; P=0.524). In addition, there were no significant differences between the groups in any secondary outcomes. However, people who reported knowing risky situations for relapse and using strategies to handle urges to smoke were less likely to relapse. CONCLUSIONS: In people who stop smoking successfully with behavioural support, a comprehensive self-help educational programme to teach people skills to identify and respond to high-risk situations for return to smoking did not reduce relapse

Modelling the atmospheric dispersion of radiotracers in small-scale, controlled detonations: validation of dispersion models using field test data

A series of modelling exercises, based on field tests conducted in the Czech Republic, were carried out by the ‘Urban’ Working Groups as part of the International Atomic Energy Agency’s Environmental Modelling for Radiation Safety II, Modelling and Data for Radiological Impact Assessment (MODARIA) I and MODARIA II international data compilation and model validation programmes. In the first two of these programmes, data from a series of field tests involving dispersion of a radiotracer, 99mTc, from small-scale, controlled detonations were used in a comparison of model predictions with field measurements of deposition. In the third programme, data from a similar field test, involving dispersion of 140La instead of 99mTc, were used. Use of longer-lived 140La as a radiotracer allowed a greater number of measurements to be made over a greater distance from the dispersion point and in more directions than was possible for the earlier tests involving shorter-lived 99mTc. The modelling exercises included both intercomparison of model predictions from several participants and comparison of model predictions with the measured data. Several models (HotSpot, LASAIR, ADDAM/CSA-ERM, plus some research models) were used in the comparisons, which demonstrated the challenges of modelling dispersion of radionuclides from detonations and the need for appropriate meteorological measurements

Nipah Virus Infection in Dogs, Malaysia, 1999

The 1999 outbreak of Nipah virus encephalitis in humans and pigs in Peninsular Malaysia ended with the evacuation of humans and culling of pigs in the epidemic area. Serologic screening showed that, in the absence of infected pigs, dogs were not a secondary reservoir for Nipah virus