PROSPECT methodology for developing procedure-specific pain management recommendations: an update.

The procedure-specific postoperative pain management (PROSPECT) working group develops evidence-based pain management recommendations. PROSPECT methodology is unique and rigorous. However, several limitations were recognised that needed to be addressed, and several new factors were identified that improved PROSPECT methodology. The aim of this article is to present updated PROSPECT methodology for development of recommendations for procedure-specific pain management, focusing on the methodological revisions we will implement. In future, included randomised clinical trials will need to be prospectively registered on a publicly accessible clinical trials database and the study design, including the primary outcome in the registration, should coincide with that in the published manuscript. Placebo-controlled studies in which the analgesic intervention of interest is solely paracetamol, non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2-specific inhibitors or opioids will not be included. Studies comparing one drug in a particular class with another in the same class will also not be included. Future projects will use the Cochrane Collaboration risk of bias tool for quality of reporting of methodology and results. A modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach will be used for grading of level of evidence and strength of recommendations. Finally, the updated PROSPECT methodology addresses several other limitations and implements new factors that all add rigour and transparency to developing procedure-specific pain management recommendations.

Isolated Tillaux Fracture in a Skeletally-Mature Patient: A Rare Presentation.

Isolated Tillaux fractures are uncommon injuries that occur due to external rotational forces acting on the ankle joint. They are more commonly seen in adolescents due to the presence of open epiphyses. In adults, isolated Tillaux fractures present as plafond fractures well described with the AO (Arbeitsgemeinschaft für Osteosynthesefragen) Classification as well as Types 1, 2, and 3 according to the degree of articular comminution present. They occur rarely and can be easily missed or misdiagnosed as other ankle injuries. A thorough clinical examination, combined with imaging studies such as X-rays and CT scans, can aid in accurate diagnosis and treatment planning. Management typically involves open reduction and internal fixation, followed by a short period of immobilization and early mobilization with non-weight bearing. We present a case report of a 27-year-old female who presented with an isolated Tillaux fracture of the ankle following a road traffic accident. This type of fracture is typically seen in teenagers and young adults due to the incomplete closure of the growth plate, which makes it more susceptible to injury. The patient underwent open reduction and internal fixation with a contoured three-hole 3.5 mm titanium T-plate, followed by immobilization in a plaster splint for one week. Early mobilization was encouraged with strict non-weight bearing for 8-10 weeks. Follow-up at 12 weeks revealed complete union at the fracture site, with the patient being asymptomatic except for minimal pain and mild restriction in dorsiflexion.

Polysaccharide and monosaccharide guided liver delivery of Sorafenib Tosylate - A nano-strategic approach and comparative assessment of hepatospecificity.

Hepatospecific delivery by ligand based receptor targeting is an established strategy to augment therapy associated with liver diseases and disorders. Previously, we have investigated the effect of ligand headgroup on cellular uptake mediated by the asialoglycoprotein receptor by in silico and in vitro approach. In this paper, we report the design of agarose based liposomes for delivery to liver cancer cells and provide a proof of concept of the targeting efficiency against galactose liposomes using an in vivo approach. Sorafenib Tosylate loaded targeting liposomes were developed and optimized using factorial design. Comparative evaluation including cell cytotoxicity, pharmacokinetics and biodistribution and hepatospecific uptake was performed for both the liposomal systems. The formulations possessed a particle size of 150 - 180 nm and a zeta potential of 30 - 60 mV depending on the amount of ligand and drug loading, with more than 90% entrapment efficiency. A two-fold increase in cytotoxicity was observed with agarose-based liposomes as compared to galactose based liposomes. In vivo PK evaluation indicated a reduction in half life of drug when loaded in agarose ligand loaded system, probably due to greater uptake in the liver as evidenced in biodistribution study. Intrahepatic disposition revealed a higher PC/NPC uptake ratio with the targeted systems as compared to conventional liposomes, although the agarose-based system resulted in highest uptake ratio. A biocompatible platform for specific delivery of drugs to hepatocytes was established validating a rational approach to design liver targeting systems.

PROSPECT guidelines for video-assisted thoracoscopic surgery: a systematic review and procedure-specific postoperative pain management recommendations.

Video-assisted thoracoscopic surgery has become increasingly popular due to faster recovery times and reduced postoperative pain compared with thoracotomy. However, analgesic regimens for video-assisted thoracoscopic surgery vary significantly. The goal of this systematic review was to evaluate the available literature and develop recommendations for optimal pain management after video-assisted thoracoscopic surgery. A systematic review was undertaken using procedure-specific postoperative pain management (PROSPECT) methodology. Randomised controlled trials published in the English language, between January 2010 and January 2021 assessing the effect of analgesic, anaesthetic or surgical interventions were identified. We retrieved 1070 studies of which 69 randomised controlled trials and two reviews met inclusion criteria. We recommend the administration of basic analgesia including paracetamol and non-steroidal anti-inflammatory drugs or cyclo-oxygenase-2-specific inhibitors pre-operatively or intra-operatively and continued postoperatively. Intra-operative intravenous dexmedetomidine infusion may be used, specifically when basic analgesia and regional analgesic techniques could not be given. In addition, a paravertebral block or erector spinae plane block is recommended as a first-choice option. A serratus anterior plane block could also be administered as a second-choice option. Opioids should be reserved as rescue analgesics in the postoperative period.

Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting - Synthesis and comparative in silico and in vitro assessment.

Ligands with the polysaccharide headgroups have been recently reported by our group to possess enhanced interaction with asialoglycoprotein receptor (ASGPR) in silico as compared to ligands having galactose moieties. This enhanced interaction is a result of the polymer's backbone support in anchoring the ligand in a specific orientation within the bilayer. In this paper, we have attempted to provide an in vitro proof of concept by performing a comparative evaluation of polysaccharide and monosaccharide-based ligands. Docking was performed to understand interaction with ASGPR in silico. Agarose and galactose conjugates with behenic acid were synthesized, purified, and characterized to yield biocompatible hepatospecific ligands which were incorporated into nanoliposomes. Cellular internalization of these targeted liposomes was studied using confocal microscopy and flow cytometry. The toxicity potential was assessed in vivo. Results indicated that the polysaccharide-based ligand increased cellular uptake due to better interaction with the receptor as compared to ligand bearing a single galactose group. In addition to developing novel liver targeting ligands, the study also established proof of concept that has been suggested by earlier in silico investigations. The approach can be used to design targeting ligands and develop formulations with improved targeting efficacy.

PROSPECT guideline for total hip arthroplasty: a systematic review and procedure-specific postoperative pain management recommendations.

The aim of this systematic review was to develop recommendations for the management of postoperative pain after primary elective total hip arthroplasty, updating the previous procedure-specific postoperative pain management (PROSPECT) guidelines published in 2005 and updated in July 2010. Randomised controlled trials and meta-analyses published between July 2010 and December 2019 assessing postoperative pain using analgesic, anaesthetic, surgical or other interventions were identified from MEDLINE, Embase and Cochrane databases. Five hundred and twenty studies were initially identified, of which 108 randomised trials and 21 meta-analyses met the inclusion criteria. Peri-operative interventions that improved postoperative pain include: paracetamol; cyclo-oxygenase-2-selective inhibitors; non-steroidal anti-inflammatory drugs; and intravenous dexamethasone. In addition, peripheral nerve blocks (femoral nerve block; lumbar plexus block; fascia iliaca block), single-shot local infiltration analgesia, intrathecal morphine and epidural analgesia also improved pain. Limited or inconsistent evidence was found for all other approaches evaluated. Surgical and anaesthetic techniques appear to have a minor impact on postoperative pain, and thus their choice should be based on criteria other than pain. In summary, the analgesic regimen for total hip arthroplasty should include pre-operative or intra-operative paracetamol and cyclo-oxygenase-2-selective inhibitors or non-steroidal anti-inflammatory drugs, continued postoperatively with opioids used as rescue analgesics. In addition, intra-operative intravenous dexamethasone 8-10 mg is recommended. Regional analgesic techniques such as fascia iliaca block or local infiltration analgesia are recommended, especially if there are contra-indications to basic analgesics and/or in patients with high expected postoperative pain. Epidural analgesia, femoral nerve block, lumbar plexus block and gabapentinoid administration are not recommended as the adverse effects outweigh the benefits. Although intrathecal morphine 0.1 mg can be used, the PROSPECT group emphasises the risks and side-effects associated with its use and provides evidence that adequate analgesia may be achieved with basic analgesics and regional techniques without intrathecal morphine.

PROSPECT guideline for elective caesarean section: updated systematic review and procedure-specific postoperative pain management recommendations.

Caesarean section is associated with moderate-to-severe postoperative pain, which can influence postoperative recovery and patient satisfaction as well as breastfeeding success and mother-child bonding. The aim of this systematic review was to update the available literature and develop recommendations for optimal pain management after elective caesarean section under neuraxial anaesthesia. A systematic review utilising procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in the English language between 1 May 2014 and 22 October 2020 evaluating the effects of analgesic, anaesthetic and surgical interventions were retrieved from MEDLINE, Embase and Cochrane databases. Studies evaluating pain management for emergency or unplanned operative deliveries or caesarean section performed under general anaesthesia were excluded. A total of 145 studies met the inclusion criteria. For patients undergoing elective caesarean section performed under neuraxial anaesthesia, recommendations include intrathecal morphine 50-100 µg or diamorphine 300 µg administered pre-operatively; paracetamol; non-steroidal anti-inflammatory drugs; and intravenous dexamethasone administered after delivery. If intrathecal opioid was not administered, single-injection local anaesthetic wound infiltration; continuous wound local anaesthetic infusion; and/or fascial plane blocks such as transversus abdominis plane or quadratus lumborum blocks are recommended. The postoperative regimen should include regular paracetamol and non-steroidal anti-inflammatory drugs with opioids used for rescue. The surgical technique should include a Joel-Cohen incision; non-closure of the peritoneum; and abdominal binders. Transcutaneous electrical nerve stimulation could be used as analgesic adjunct. Some of the interventions, although effective, carry risks, and consequentially were omitted from the recommendations. Some interventions were not recommended due to insufficient, inconsistent or lack of evidence. Of note, these recommendations may not be applicable to unplanned deliveries or caesarean section performed under general anaesthesia.

Computational study of the intermolecular interactions and their effect on the UV-visible spectra of the ternary liquid mixture of benzene, ethanol and propylene glycol.

Quantum chemical calculations are well-equipped to provide answers to the questions regarding the different aspects of intermolecular interactions. We investigate the benzene, ethanol and 1,2 propanediol ternary mixture with theoretical as well as experimental UV-Vis spectroscopy. An extensive theoretical study on the molecular structure and UV-Vis spectral analysis was undertaken using density functional theory (DFT) method. Structural parameter analysis and the HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) energy gap help to describe the possible interaction between molecules in dimer and in combination. Interaction energy has been calculated from topological study. Time-dependent density functional theory (TDDFT) calculations on dimer/cluster in gas phase help to understand the effect of the molecular interaction on the overall spectral shift and related intensity variation. Our results show that in the ternary mixture, the interaction energies of the interactions are π-π interaction: 0.52-2.57 kcal/mol, Hp-π interaction: 1.15 kcal/mol and H-bonding: 2.49 to 4.46 kcal/mol. The π-π interaction and H-bonding cause red shift in absorption spectra while Hp-π interaction causes blue shift. In the ternary mixture, the strength of different kinds of interaction depends on the concentration, and as each interaction has its own effect on spectral shift, the overall experimental spectra get broader and distorted from the Gaussian shape.

Adjustable coupling and in situ variable frequency electron paramagnetic resonance probe with loop-gap resonators for spectroscopy up to X-band.

In standard electron paramagnetic resonance (EPR) spectroscopy, the frequency of an experiment is set and the spectrum is acquired using the magnetic field as the independent variable. There are cases in which it is desirable instead to fix the field and tune the frequency such as when studying avoided level crossings. We have designed and tested an adjustable frequency and variable coupling EPR probe with loop-gap resonators (LGRs) that works at a temperature as low as 1.8 K. The frequency is tuned by adjusting the height of a dielectric piece of sapphire inserted into the gap of an LGR; coupling of the microwave antenna is varied with the height of the antenna above the LGR. Both coupling antenna and dielectric are located within the cryogenic sample chamber, but their motion is controlled with external micrometers located outside the cryostat. The frequency of the LGR (∼4 GHz) can be adjusted by more than 1 GHz (>25%). To cover a wide range of frequencies, different LGRs can be designed to cover frequencies up to X-band. We demonstrate the operation of our probe by mapping out avoided crossings for the Ni4 molecular nanomagnet to determine the tunnel splittings with high precision.