What is the impact of dexamethasone on postoperative pain in adults undergoing general anaesthesia for elective abdominal surgery: a systematic review and meta-analysis.

BACKGROUND: Previous meta-analysis of heterogeneous surgical cohorts demonstrated reduction in postoperative pain with perioperative intravenous dexamethasone, but none have addressed adults undergoing elective abdominal surgery. The aim of this study was to determine the impact of intravenous perioperative dexamethasone on postoperative pain in adults undergoing elective abdominal surgery under general anaesthesia. METHODS: This review was prospectively registered on the international prospective register of systematic reviews (CRD42020176202). Electronic databases Medical Analysis and Retrieval System Online (MEDLINE), Exerpta Medica Database (EMBASE), (CINAHL) Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and trial registries were searched to January 28 2021 for randomised controlled trials, comparing dexamethasone to placebo or alternative antiemetic, that reported pain. The primary outcome was pain score, and secondary outcomes were time to first analgesia, opioid requirements and time to post-anaesthesia care unit (PACU) discharge. RESULTS: Fifty-two studies (5768 participants) were included in the meta-analysis. Pain scores ≤ 4 hour (h) were reduced in patients who received dexamethasone at rest (mean difference (MD), - 0.54, 95% confidence interval (CI) - 0.72 to - 0.35, I2 = 81%) and on movement (MD - 0.42, 95% CI - 0.62 to - 0.22, I2 = 35). In the dexamethasone group, 4-24 h pain scores were less at rest (MD - 0.31, 95% CI - 0.47 to - 0.14, I2 = 96) and on movement (MD - 0.26, 95% CI - 0.39 to - 0.13, I2 = 29) and pain scores ≥ 24 h were reduced at rest (MD - 0.38, 95% CI - 0.52 to - 0.24, I2 = 88) and on movement (MD - 0.38, 95% CI - 0.65 to - 0.11, I2 = 71). Time to first analgesia (minutes) was increased (MD 22.92, 95% CI 11.09 to 34.75, I2 = 98), opioid requirements (mg oral morphine) decreased (MD - 6.66, 95% CI - 9.38 to - 3.93, I2 = 88) and no difference in time to PACU discharge (MD - 3.82, 95% CI - 10.87 to 3.23, I2 = 59%). CONCLUSIONS: Patients receiving dexamethasone had reduced pain scores, postoperative opioid requirements and longer time to first analgesia. Dexamethasone is an effective analgesic adjunct for patients undergoing abdominal surgery.

Development of a Core Outcome Set for studies evaluating the effects of anaesthesia on perioperative morbidity and mortality following hip fracture surgery.

BACKGROUND: Perioperative studies of patients following hip fracture have large heterogeneity within their reported outcomes. This study aimed to develop a core outcome set for use in perioperative studies comparing the types of anaesthesia for hip fracture surgery. METHODS: The consensus process consisted of a systematic review of the literature, three rounds of a Delphi survey, two consensus webinars, and face-to-face patient meetings. RESULTS: The Delphi participants represented nine stakeholder groups. The numbers of participants completing Rounds 1-3 were 242, 186, and 169, respectively. Seventeen outcomes that met the predefined consensus criteria were considered at two consensus meetings. A final set of 10 core outcomes was agreed: mortality, time from injury to surgery, acute coronary syndrome, hypotension, acute kidney injury, delirium, pneumonia, orthogeriatric input, being out of bed at day 1, and pain. CONCLUSIONS: We generated a consensus-based set of core outcomes recommended for use in all perioperative trials evaluating the effects of anaesthesia for hip fracture surgery. An important next step is developing consensus-based consistency on how they should be measured. CLINICAL TRIAL REGISTRATION: http://www.comet-initiative.org/studies/details/757.

Perioperative outcomes in the context of mode of anaesthesia for patients undergoing hip fracture surgery: systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses on the anaesthetic management of patients undergoing surgery for hip fracture have focused on randomized trials. Furthermore, heterogeneity in outcome reporting across the studies has made it difficult to inform best practice guidelines for patient care. METHODS: This systematic review examined how perioperative outcomes were reported and defined in the context of comparing modes of anaesthesia for hip fracture surgery. Outcomes were included from randomised and non-randomised studies published between January 2000 and July 2017. Meta-analyses were performed for regional versus general anaesthesia, with sensitivity analyses performed for spinal versus general anaesthesia. RESULTS: By including data from 15 large observational studies in this meta-analysis, we have increased the number of patients for whom outcomes were assessed from approximately 3000 to 202 000. There was no significant difference in 30-day mortality (OR 1.02; 95% CI 0.96, 1.07, I2 31%; n=200 616), prevalence of pneumonia (OR 1.07; 95% CI 0.94, 1.23, I2 34%; n=65 011), acute myocardial infarction (OR 0.96; 95% CI 0.88, 1.04, I2 0%, n=64 904), delirium (OR 1.07; 95% CI 0.72, 1.58, I2 93%, n=19 923), or renal failure (OR 0.94; 95% CI 0.54, 1.64, I2 0%, n=27 873) for regional compared with general anaesthesia [corrected]. There was a small statistically significant difference for length of stay (standardized mean difference -0.03; 95% CI -0.05, -0.02; I2 0%; n=78 711) favouring regional anaesthesia, which is unlikely to be clinically significant. Sensitivity analyses for the same outcomes examining spinal only vs general anaesthesia showed minor statistical significance for length of stay favouring spinal. We also present data highlighting the scale of the inconsistencies in reported outcomes across 32 studies, making evaluation in a standardized manner very difficult. As an example, mortality was reported in nine different ways throughout the studies. CONCLUSIONS: We highlight the need for agreement on outcome definitions and for a minimum core outcome set to be measured and reported in hip fracture studies. This would strengthen the evidence-based approach to delivering optimal care.

Ileocolonic neuroendocrine tumours identified in the English bowel cancer screening programme.

AIM: Ileocolonic neuroendocrine tumours (NETs) are diagnosed as part of bowel cancer screening programmes (BCSPs). The aim of this study was to identify and characterize NETs diagnosed within the English BCSP, a double-screen programme that uses guaic faecal occult blood test (gFOBT) screening and colonoscopy, by interrogating the national colorectal screening database and validating the findings with individual BCSP centres. METHOD: The Exeter database was interrogated by running queries to identify participants with coded NETs (from the start of the programme in July 2006 - 1 December 2014). A written proforma was sent to the responsible BCSP clinician for validation and characterization. RESULTS: During this period, 13 061 716 participants were adequately screened using gFOBTs, and 259 765 participants had definitively abnormal results. There were 146 unique participants with NET-related codes from 216 707 BCSP colonoscopies. The diagnosis rates per 100 000 colonoscopies were 29 rectal, 18 colonic and 11 ileal NETs. The majority of rectal NETs had Grade 1 (80%) and Stage T1 (85.1%) disease. Over half of ileal NETs (53.6%) in this study had invasive disease, with 85.2% having nodal and 36.1% having metastastatic disease. CONCLUSION: The current study highlights the rate of colorectal NETs diagnosed in the English BCSP. These data highlight a higher-than-anticipated incidence, and the potential additional benefit of BCSPs in identifying occult NETs.

Validation of the EORTC QLQ-BIL21 questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder.

BACKGROUND: There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice. METHODS: This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder. Patients completed the questionnaire at baseline pretherapy and subsequently at 2 months. Following this, the psychometric properties of reliability, validity, scale structure and responsiveness to change were analysed. RESULTS: Analysis of the QLQ-BIL21 scales showed appropriate reliability with Cronbach's α-coefficients >0.70 for all scales overall. Intraclass correlations exceeded 0.80 for all scales. Convergent validity >0.40 was demonstrated for all items within scales, and discriminant validity was confirmed with values <0.70 for all scales compared with each other. Scale scores changed in accordance with Karnofsky performance status and in response to clinical change. CONCLUSIONS: The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder.

An outpatient low-intensity locomotor training programme for paediatric chronic incomplete spinal cord injury.

STUDY DESIGN: Single case study. OBJECTIVES: Intensive locomotor training programmes have recently been implemented in paediatric settings for patients with chronic incomplete spinal cord injury. This case study examines whether a lower-intensity locomotor training programme can improve functional ambulation. SETTING: Tertiary care setting in Melbourne, Australia. METHODS: A pretest-post-test design was used for a 17-year-old boy, 16 months after incomplete spinal injury at T6, who was classified as American Spinal Injury Association (ASIA) level C. He participated in two weekly sessions of locomotor training for a period of 6 weeks. Lower Extremity Motor Score (LEMS), Walking Index for Spinal Cord Injury (WISCI II), 6-min walk test (6MWT), 10-m walk test (10MWT), Timed Up and Go (TUG), and the PedsQL were measured before training, immediately after training and 6 weeks after training had ceased. RESULTS: The WISCI II score improved from 6 at baseline to 9 immediately post treatment and this was maintained at follow-up. The PedsQL score was also significantly improved immediately post treatment and at 6 weeks follow-up. The LEMS and 6MWT improved after the intervention also. CONCLUSION: This case study provides evidence of improvements following a less-intensive locomotor training programme in an outpatient setting. Studies with larger samples are required to fully examine the benefits of this programme.

Lipopolysacchride-treated mammary carcinomas secrete proinflammatory chemokines and exhibit reduced growth rates in vivo, but not in vitro.

Toll-like receptors (TLR) are pattern recognition receptors that play a pivotal role in the initiation of immune responses. Here we report that the murine mammary carcinoma 4T1 constitutively expressed genes encoding TLR2, 3, 4 and 5. Moreover, treatment of the 4T1 cell line with peptidoglycan (PGN), polyinosinic-polycytidylic acid (Poly(I:C)) or lipopolysaccharide (LPS), agonists for TLR2, 3 or 4 respectively, induced nuclear translocation of NFkappaB and secretion of CCL2, CCL5 and CXCL1 in a dose dependent manner. Although treating the tumor cells with the TLR agonists did not modulate growth or viability of the tumor cells in vitro, 4T1 exhibited a decreased growth rate in vivo following treatment with LPS that was dependent upon the presence of CD8(+) T cells. Analysis of 3 additional murine mammary carcinomas revealed that they also secreted CCL2, CCL5 and CXCL1 in response to TLR agonist treatment, and LPS treated 168 and SM1 tumors exhibited decreased growth rates in vivo, but not in vitro. These data indicated that 4 out of 4 murine mammary carcinomas secreted proinflammatory chemokines following treatment with TLR agonists, and 3 out of 4 of the mammary carcinomas responded to LPS treatment in a manner that decreased tumor growth in vivo.

Clinical evaluation of Toxi.Prep: a semiautomated solid-phase extraction system for screening of drugs in urine.

A prototype Toxi.Prep (TP) system that utilizes solid-phase extraction (SPE) has been developed as a method for broad-spectrum drug screening and identification of tetrahydrocannabinol (THC) metabolites in urine. TP can simultaneously extract up to seven specimens while automating the process of sample extraction, washing, and elution onto a chromatogram. TP was compared with the Toxi. Lab A (TL-A) system for extraction of basic drugs only. In a blind study, 33 distinct drugs and metabolites were detected in 55 urines over 13 runs. Of the drug occurrences, 68.8% (141 of 205) were detected on both TP and TL-A. Of the 13 runs, quinidine and quinine, nortriptyline metabolites, and diphenhydramine were noted more frequently on TP than TL-A, whereas nicotine and metabolites, morphine, and methadone metabolites were more frequently noted on TL-A. Twenty specimens were analyzed for THC metabolites. Of the cases positive for THC metabolites, 100% (16 of 16) were positive by both methods. Time and motion studies for all runs proved an overall labor reduction for extraction and spotting by approximately 40%.

An evaluation of a short course in resuscitation training in a district general hospital.

One hundred nurses underwent a short form of cardiopulmonary resuscitation training, comprising a short lecture and practical training. This significantly improved theoretical knowledge, but failed to achieve a uniformly high standard of practical skill. After initial training the subjects were divided into three groups. Group 1 underwent monthly refresher sessions, Group 2 a single refresher at 3 months and Group 3 no refresher training prior to re-testing of all subjects at 6 months. Knowledge and skills had declined in all three groups. Theoretical scores were better preserved in the groups having refresher training. Frequent refresher training failed to improve the poor initial performance in the practical skills. The time required to produce adequate training is greater than that which can be provided by clinical staff and necessitates the appointment of a resuscitation training officer.

Nitrosating activity in Escherichia coli.

Nitrosation activity was measured in Escherichia coli isolates and a range of nitrite reductase (nir) mutants. Activity was only detected in intact cells and could be inhibited by a number of treatments such as sonication and osmotic shock. Aerobically-grown cells had highest nitrosation activity compared to oxygen-limited ones. Inclusion of nitrite in growth media induced high activities of nitrite reductase and for some isolates, nitrosation. Analysis of nir mutants identified two which were unable to nitrosate. This result suggested that NADH-dependent nitrite reductase was implicated either directly or indirectly in nitrosation.

Industrial employee drug screening: a blind study of laboratory performance using commercially prepared controls.

Reference laboratories are an integral component of any industrial employee drug screening program. We evaluated the performance and accuracy of the reference laboratories used by Rockwell International, a large industrial employer with an active drug screening program. A total of 829 commercially prepared control samples containing drugs of abuse, over-the-counter drugs, and analytes found in the normal employee population were disguised as routine submissions to reference laboratories used by nine Rockwell facilities. Analyses of results included compilation of false-positive and false-negative errors per drug per laboratory and a correlation of errors with preliminary and confirmation methods. Error rates of 2% false-positive results and 20% false-negative results were found for all laboratories. The errors were not limited to any one technique nor to any particular drug. The error rates observed suggest the need for routine blind testing programs and increased interaction between industry and laboratories.

A rapid sample-preparation technique for thin-layer chromatographic analysis for 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in human urine.

In this rapid TLC method of analysis for the urinary cannabinoid metabolite, 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), hydrolyzed urine specimens are aspirated through a porous, alkyl-silica extraction layer located along the lower edge of a biphasic thin-layer chromatogram; THC-COOH is simultaneously extracted from the sample and concentrated on the TLC plate for subsequent migration and detection. The method, evaluated in a blind study, identified all samples containing THC-COOH greater than or equal to 20 micrograms/L. The technique increases samples throughput, sensitivity, and specificity as compared with conventional TLC methods and is applicable to a wide variety of compounds.

Evaluation of a multiple-variable thin-layer and reversed-phase thin-layer chromatographic scheme for identification of basic and neutral drugs in an emergency toxicology setting.

An analytical scheme composed of one normal-phase thin-layer chromatographic (TLC) method, one reversed-phase thin-layer chromatographic (RPTLC) method, and sequential analyte detection through four stages of color reactions is described. Eighty-one basic or neutral drugs were analyzed with this scheme and seventy-four were uniquely characterized with 95% confidence. Six of the remaining seven formed three unresolved pairs. The scheme was evaluated by mean list length analysis and shown to offer analyte resolution similar to that of a scheme of TLC and gas chromatography (GC) with nonspecific detection. Nine out of ten unknowns from the field of eighty-one drugs were uniquely identified with 95% confidence by the TLC/RPTLC scheme. The tenth unknown was not completely resolved from its isomer, but was statistically the more probable candidate.

Nanomelic chondrocytes synthesize a glycoprotein related to chondroitin sulfate proteoglycan core protein.

Chicken embryos homozygous for the autosomal recessive gene nanomelia exhibit cartilage defects, synthesize low levels of cartilage chondroitin sulfate proteoglycan (CSPG), and are missing the CSPG core protein (Argraves, W. S., McKeown-Longo, P. J., and Goetinck, P. F. (1981) FEBS Lett. 131, 265). In our studies of nanomelic chondrocytes in culture, we detected neither sulfate-labeled CSPG nor its Mr 370,000 core protein. However, in immunoprecipitation reactions using both polyclonal and monoclonal antibodies directed against the cartilage CSPG core protein, we identified a protein of Mr 300,000 that contains an epitope found in the hyaluronic acid-binding region of the normal core protein. This protein was also detected among products synthesized by chondrocytes obtained from phenotypically normal embryos resulting from matings between parents heterozygous for nanomelia. Sensitivity to endoglycosidase H indicated that the product is a glycoprotein with attached mannose-rich oligosaccharides. Pulse-chase studies revealed the disappearance of the glycoprotein after 6 h of chase, but no detectable formation of proteoglycan. Our results suggest that although nanomelic chondrocytes are deficient in the production of normal CSPG and its core protein, they do synthesize a smaller, immunologically related glycoprotein that does not undergo the post-translational processing characteristic of the normal cartilage core protein.

Confirmation and certainty in toxicology screening.

Confirmation of presumptive positive urine drug screens, necessary to minimize the reporting of false-positive results, can be costly and time-consuming. The predictive value model can be used to select the confirming tests and to calculate the confidence of the result. The predictive value of a test result is the probability, based on the sensitivity and specificity of the test, that the result is a true positive or a true negative. The predictive value model applied to toxicology screening tests for drugs of abuse showed that prevalence, in addition to sensitivity and specificity, was the factor controlling the confidence level of a result. For example, the predictive value of a positive result for a screening test that has a sensitivity of 99% and a specificity of 99%, applied to screening in a population with a prevalence of 1% is 0.50; for a prevalence of 10%, it is 0.92. Confirmation with a second, chemically independent, test of equal sensitivity and specificity increases the predictive value to 0.99.

Laboratory detection of cannabinoids.

Cannabis, or marijuana, has been known and used as a drug for many thousands of years. Recent interest in drug abuse and detection has spurred the development of several methodologies for cannabinoid detection. These methods include immunoassays and chromatography. Laboratories routinely performing cannabinoid testing use two or more methodologies; the accepted method is to screen with one methodology and confirm by a second. These methodologies vary widely in sensitivity, specificity, and time required for analysis. Although therapeutic applications of cannabis constituents often produce undesirable side effects, two cannabinoids, delta 9-THC and nabilone, have been approved for use as antiemetics in chemotherapy. Further investigations of cannabinoid pharmacology and structure-activity relationships may result in the development of promising new therapeutic agents.

In-vitro production of nitrosamines by bacteria isolated from the operated stomach.

Evidence is presented of in-vitro catalysis of nitrosation by organisms isolated from the hypoacidic operated stomach. Subjects taking part in a prospective study of potential premalignancy after benign ulcer surgery underwent endoscopy, and samples of gastric juice were obtained aseptically. The organisms present were identified using the API system and tested for their ability to catalyse the nitrosation of the secondary amine, morpholine, at neutral pH and 37 degrees C. Four of the five species tested were found to be capable of the catalysis. Cellular disruption and denaturation of protein abolished the catalytic ability, suggesting that the catalysis is mediated by an enzymic system. Osmotic shock experiments indicate that the enzyme site may be on the inner membrane.

An investigation of possible risk factors associated with gastric cancer after benign ulcer operations.

The risk of developing gastric cancer has been investigated in a case-control study and in a prospective investigation. In the case-control study, 1495 cases of gastric cancer were identified in five city hospitals and matched with autopsy controls from the same hospitals. The frequency of operations for benign ulcer [partial gastrectomy (PG) and gastroenterostomy] was similar in the two groups. Thus, there was no increased risk for late gastric cancer after an ulcer operation. A total of 140 operated ulcer subjects [80 truncal vagotomy and drainage (TVD), 60 PG and 78 nonoperated cases attending with dyspepsia (C)] were examined by endoscopy, multiple gastric biopsy and analysis of gastric juice for nitrite. Biopsies were graded for gastritis and a gastritis index was derived (normal, 1; superficial gastritis, 2; chronic atrophic gastritis: mild, 3; moderate, 4; severe, 5). More atrophic gastritis was found in operated subjects than in controls: TVD, 2.3 +/- 0.08 (mean +/- SE); PG, 2.6 +/- 0.1 versus C, 1.8 +/- 0.08, p less than 0.01. The severity of atrophic gastritis increased after an operation interval of 20 years in PG subjects (p less than 0.05). Intestinal metaplasia was a common change, but unequivocal epithelial dysplasia was not observed. Two cases of operated stomach cancer were found. High levels of nitrite were positively correlated with pH and a high gastritis index. This evidence does not suggest that ulcer surgery leads to either an increased risk of cancer or a precancerous condition.