Formulation and Permeation Kinetic Studies of Flurbiprofen Gel

Purpose: To investigate the in vitro permeation and drug release kinetics of flurbiprofen gel.Methods: Thirteen batches (G1, G2 … G13) of flurbiprofen gels were prepared using different ratios ofpermeation enhancers, i.e., propylene glycol (PG) and polyethylene glycol (PEG), by response surface methodology (RSM). Viscosity, pH, spreadability, consistency and drug content of the flurbiprofen gels were measured. Permeation experiments were conducted using silicone membrane in a modified Franz diffusion cell. Permeation parameters determined include diffusion coefficient (D), Flux (J), lag time (tLag), permeation coefficient (Kp), input rate (IR) and enhancement ratio (ER). Primary skin irritation test was performed for the optimized gel, G3, using 11 human volunteers.Results: Maximum solubility (72.15 ± 0.02 mg/mL) of flurbiprofen was observed in a mixture (2:1) of methanol and water. Partition coefficient (Ko/w) was determined as logP = 3.68 ± 0.11. The gels were stable under various storage conditions, and were homogenous, crystalline and transparent. Viscosity, pH, spreadability, consistency and drug content were in the range of 150 – 178 × 102 cps, 5.42 - 5.75, 5.0 - 7.0 g.cm/s, 3.0 - 9.0 mm, and 97.99 - 99.86 %, respectively. No irritation or lesions (erythma, redness and ulceration) occurred in human volunteers over a 30-day period. The optimized formulation, G3, showed maximum flux through silicone membrane.Conclusion: PG and PEG are effective enhancers of flurbiprofen from  various formulations when used in various ratios.Keywords: Flurbiprofen, Gel, Diffusion, Permeation enhancers, Skin irritation, Silicone membran

Comprehensive glycosylation profiling of IgG and IgG-fusion proteins by top-down MS with multiple fragmentation techniques

We employed top- and middle-down analyses with multiple fragmentation techniques including electron transfer dissociation (ETD), electron capture dissociation (ECD), and matrix-assisted laser desorption ionization in-source decay (MALDI-ISD) for characterization of a reference monoclonal antibody (mAb) IgG1 and a fusion IgG protein. Fourier transform ion cyclotron resonance (FT-ICR) or high performance liquid chromatography electrospray ionization (HPLC-ESI) on an Orbitrap was employed. These experiments provided a comprehensive view on the protein species; especially for different glycosylation level in these two proteins, which showed good agreement with oligosaccharide profiling. Top- and middle-down MS provided additional information regarding glycosylation sites and different combinational protein species that were not available from oligosaccharide mapping or conventional bottom-up analysis. Finally, incorporating a limited enzymatic digestion by immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS) with MALDI-ISD analysis enabled extended sequence coverage of the internal region of protein without pre-fractionation. Biological significance: Oligosaccharide profiling together with top- and middle-down methods enabled: 1) detection of heterogeneous glycosylated protein species and sites in intact IgG1 and fusion proteins with high mass accuracy, 2) estimation of relative abundance levels of protein species in the sample, 3) confirmation of the protein termini structural information, and 4) improved sequence coverage by MALDI-ISD analysis for the internal regions of the proteins without sample pre-fractionation

Application of a new system for classifying root canal morphology in undergraduate teaching and clinical practice: a national survey in Malaysia

Aim To evaluate and compare the feedback of final year undergraduate dental students in eight Malaysian dental schools on the application of a new system for classifying root canal morphology in teaching and clinical practice. Methods One PowerPoint presentation describing two classification systems for root canal morphology (Oral Surgery Oral Medicine Oral Pathology, 1974 38, 456 and its supplemental configurations, International Endodontic Journal 2017, 50, 761) was delivered to final year undergraduate dental students in eight dental schools in Malaysia by two presenters (each presented to four schools). To examine students’ feedback on the utility of each system, printed questionnaires consisting of six questions (five multiple choice questions and one open‐ended question) were distributed and collected after the lecture. The questionnaire was designed to compare the classification systems in terms of accuracy, practicability, understanding of root canal morphology and recommendation for use in pre‐clinical and clinical courses. The exact test was used for statistical analysis, with the level of significance set at 0.05 (P = 0.05). Results A total of 382 (out of 447) students participated giving a response rate of 86%. More than 90% of students reported that the new system was more accurate and more practical compared with the Vertucci system (P 0.05). The students’ responses for all questions were almost similar for both presenters (P > 0.05). Conclusions The new system of International Endodontic Journal 2017, 50, 761 for classifying root and canal morphology was favoured by final year undergraduate dental students in Malaysia. The new system has the potential to be included in the undergraduate endodontic curriculum for teaching courses related to root and canal morphology

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Outcomes of obstructed abdominal wall hernia: results from the UK national small bowel obstruction audit

Background: Abdominal wall hernia is a common surgical condition. Patients may present in an emergency with bowel obstruction, incarceration or strangulation. Small bowel obstruction (SBO) is a serious surgical condition associated with significant morbidity. The aim of this study was to describe current management and outcomes of patients with obstructed hernia in the UK as identified in the National Audit of Small Bowel Obstruction (NASBO). Methods: NASBO collated data on adults treated for SBO at 131 UK hospitals between January and March 2017. Those with obstruction due to abdominal wall hernia were included in this study. Demographics, co-morbidity, imaging, operative treatment, and in-hospital outcomes were recorded. Modelling for factors associated with mortality and complications was undertaken using Cox proportional hazards and multivariable regression modelling. Results: NASBO included 2341 patients, of whom 415 (17·7 per cent) had SBO due to hernia. Surgery was performed in 312 (75·2 per cent) of the 415 patients; small bowel resection was required in 198 (63·5 per cent) of these operations. Non-operative management was reported in 35 (54 per cent) of 65 patients with a parastomal hernia and in 34 (32·1 per cent) of 106 patients with an incisional hernia. The in-hospital mortality rate was 9·4 per cent (39 of 415), and was highest in patients with a groin hernia (11·1 per cent, 17 of 153). Complications were common, including lower respiratory tract infection in 16·3 per cent of patients with a groin hernia. Increased age was associated with an increased risk of death (hazard ratio 1·05, 95 per cent c.i. 1·01 to 1·10; P = 0·009) and complications (odds ratio 1·05, 95 per cent c.i. 1·02 to 1·09; P = 0·001). Conclusion: NASBO has highlighted poor outcomes for patients with SBO due to hernia, highlighting the need for quality improvement initiatives in this group