Butorphanol for Post-Operative Analgesia - A Comparative Clinical Study with Ketorolac

Introduction: Butorphanol, an opioid derivative has been shown to have, in addition to its analgesic properties, several other advantageous effects like antistressor, sedative and anti-shivering action. The efficacy and safety profile of ketorolac, yet another widely used post-operative analgesic is well documented. This study aims to compare the two analgesics. Aims and objectives: This study was conducted to compare the analgesic efficacy and other effects of butorphanol and ketorolac, administered intramuscularly, in post-operative patients who have undergone lower abdominal and pelvic surgeries. Materials and methods: 50 patients undergoing lower abdominal and pelvic surgeries under general or spinal anaesthesia were randomly divided into two Groups (25 each). At a particular level of post-operative pain, the patients Groups I and II were administered intramuscular ketorolac 30mg and butorphanol 2mg respectively. The analgesic effect was studied using Visual Analogue Scale (VAS) and the verbal category scale. Patients were monitored for the sedative action, respiratory status and other vital parameters for 300 minutes and for other adverse reactions over the next twelve hours. Observations: Butorphanol provided better analgesia within the first two hours of administration, while ketorolac was more effective at 4-5 hours. Better sedative action without any significant respiratory depressant effect was demonstrated with butorphanol. There were no clinically significant hemodynamic fluctuations or adverse reactions with butorphanol or ketorolac. Conclusions: Butorphanol provides better early analgesia as compared to ketorolac with a desirable and safe sedative effect in post-operative patients who have undergone lower abdominal and pelvic surgeries

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

An Iterative Technique for Improved Two-level Logic Minimization

In this paper, we describe an iterative heuristic technique to improve the quality of results obtained during two-level logic minimization using ESPRESSO. Although ESPRESSO minimizes the number of cubes in the solution e#ectively, there are several problem instances where its results are worse than the Quine-McCluskey based exact minimization technique. Our technique is designed to improve the results of ESPRESSO while utilizing ESPRESSO's Unate Recursive Paradigm based optimization heuristics, on account of their simplicity and power. Our technique is based on performing a series of iterations of ESPRESSO, in each of which we extract a number of cubes and append them into a HYPER-COVER. For the given (and subsequent) iterations of ESPRESSO, these cubes are considered as don't care cubes. By e#ectively selecting the number of iterations performed by our heuristic, we can trade o# the improvement in solution quality against the run-time of our algorithm. We have implemented several variants of our iterative algorithm, and have compared their e#ectiveness. We show that with a small number of iterations, our technique is able to improve on the number of cubes in the solution, with an acceptable run-time overhead. The best variant is able to improve the ESPRESSO cube count by up to 18%, with an acceptable increase in run-time. In 58 examples where the ESPRESSO results can be potentially improved, one of the variants of our algorithm demonstrated better results than ESPRESSO for 27 cases

Intra-operative haemodynamic volatility in a patient undergoing retroperitoneal cyst excision

Excision of a suspected retroperitoneal, duodenal duplication cyst was performed in a pre-operatively normotensive patient under combined epidural and general anaesthesia. Intraoperatively, the cystic tumour was discovered to be a retroperitoneal mass, free from duodenal or adrenal origin. Development of severe arrhythmias, ST segment changes and hypertensive spikes during cyst handling and dissection suggested the possibility of a catecholamine-secreting tumour. These were managed effectively with pharmacological agents. Subsequently, histopathology of the specimen revealed a paraganglioma. Vasoactive tumour has to be suspected in every patient undergoing anaesthesia for retroperitoneal cystic lesion

Penetrating abdominal injury in a polytrauma patient: Anaesthetic challenges faced

Penetrating abdominal injuries are potentially life threatening due to the associated hemorrhagic shock and visceral injury. Through and through penetrating injury with polytrauma is rarely encountered. We report a case presenting with in situ projecting heavy metallic rod in a through and through penetrating abdominal injury along with foreign body in a road traffic accident. Anaesthetic management was difficult due to inability to position in supine, rapidly progressing hemorrhagic shock and hypoxia due hemopneumothorax. Two operating tables were used with adequate intervening space to accommodate the posteriorly projecting metallic rod during intubation in supine position. Intensive monitoring and resuscitation resulted in uneventful successful outcome

Sevoflurane versus isoflurane in shoulder arthroscopy in beach chair position in patients with prior interscalene brachial plexus block: A prospective randomised equivalency-based haemodynamic evaluation trial

Background and Aims: There is a paucity of literature on comparative effects of different inhalational anaesthetics in beach chair position (BCP) for shoulder arthroscopy. We aimed to investigate and compare the haemodynamic effects, anaesthetic and surgical outcomes between two inhalational agents. Methods: In this randomised study, patients of age 18–60 years, were allotted to two groups (29, sevoflurane and 28, isoflurane) and received protocol-based anaesthesia. Intraoperatively, different haemodynamic and other data were recorded. Results: All mean of averages of individual subject's vitals were comparable between the groups [P = 0.681, 0.325, 0.803, and 0.051, respectively for systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR)]. Higher mean HR was recorded for maximum readings of isoflurane (P = 0.028). Equivalency was observed for SBP, MBP, and DBP (P = 0.000, 002, and 0.027, respectively). Process capability indices indicated that sevoflurane had better values (Pp: 0.55 versus 0.41, Ppk: 0.35 versus 0.22) for SBP as with MBP (Pp: 0.62 versus 0.51, Ppk: 0.36 versus 0.33). For achieving optimal vision, higher pump pressures (PPs) were demanded by surgeon (P = 0.025) and higher differences observed between initial and highest PPs (P = 0.027), in isoflurane subjects. Multivariable analysis revealed that no continuous predictor was able to predict the quality of vision except additional pump flow factor, for both groups. Conclusion: Both inhalational agents demonstrated equivalent haemodynamic effects. Increased arthroscopic PP requirements were observed with isoflurane anaesthesia. Sevoflurane may be superior to isoflurane during BCP arthroscopy