Formulation, characterization and in vivo evaluation of novel edible dosage form containing nebivolol HCl

O objetivo deste trabalho foi desenvolver um gel comestível para veiculação de cloridrato de nebivolol, com características reológicas adequadas, que podem fornecer meio de administrar o fármaco em casos de disfagia orofaríngea e pacientes geriátricos. Géis comestíveis foram preparados utilizando goma gelana de baixa acetilação e citrato de sódio, em diferentes concentrações. Estudou-se o efeito da concentração da solução no tempo de gelificação, a viscosidade e a liberação do fármaco. A formulação otimizada apresentava consistência de pudim, o que é considerado adequado para pacientes disfágicos como sugerido pela National Dysphagia Diet Task Force. A formulação otimizada contendo 0,4% (m/v) de goma gelana e 0,3% (m/v) de citrato de sódio mostrou que mais de 95% de fármaco foi liberado em 20 minutos. Esta formulação também mostrou, significativamente, melhor perfil farmacocinético, quando comparado com os comprimidos convencionais comercializados administrados a coelhos brancos neozelandeses (n = 3). A formulação otimizada manteve-se estável durante 6 meses, armazenada a 25 oC ± 0,2 °C/60 ± 5% de UR. A partir deste estudo, conclui-se que a nova forma de gel comestível contendo cloridrato de nebivolol pode ser mais eficaz no tratamento de hipertensão em pacientes portadores de disfagia.The objective of this investigation was to develop a novel oral edible gel dosage form for nebivolol hydrochloride, with suitable rheological characteristics that can provide a means of administering the drug to dysphagic and geriatric patients. Edible gels were prepared using low acetylated gellan gum and sodium citrate in different concentrations. The effect of concentration of the solution on gelation time, viscosity, and drug release was studied. Optimized formulation had "spoon thick" consistency that is considered suitable for dysphagic patients as suggested by National Dysphagia Diet Task Force. The optimized formulation containing gellan gum (0.4 % w/v) and sodium citrate (0.3 % w/v) showed more than 95% drug release in 20 minutes. This formulation also showed significantly better pharmacokinetic profile when compared to marketed conventional tablets in New Zealand white rabbits (n = 3). Optimized formulation was found stable for 6 months when stored at 25 °C ± 0.2 °C/60 ± 5% RH. From this study, it can be concluded that the novel edible gel dosage form containing nebivolol hydrochloride may prove to be more efficacious in the treatment of hypertension in dysphagic patients

Extramedullary leukemia in children presenting with proptosis

<p>Abstract</p> <p>Background</p> <p>We highlight the orbital manifestations of acute myeloid leukemia and the role of peripheral blood smear in the diagnosis of these cases. A total of 12 patients who presented with proptosis and were subsequently diagnosed to have acute myeloid leukemia based on incision biopsy or peripheral blood smear were included in the study.</p> <p>Results</p> <p>A retrospective review of all cases of acute myeloid leukemia presenting to the Orbital clinic was performed. The age at presentation, gender, presenting features, duration of symptoms and fundus features were noted. In addition the temporal relationship of the orbital disease to the diagnosis of leukemia, laterality, location of the orbital mass, imaging features and the diagnostic tools used to diagnose leukemia were noted. The median age at presentation was 6 years. The male: female ratio was 0.7:1. None of these patients had been diagnosed earlier as having acute myeloid leukemia. The presenting features included proptosis in all patients, orbital mass in 5 (41.7%), visual symptoms in 2 (16.7%) and subconjunctival hemorrhage in one patient (8.3%). A diagnosis of acute myeloid leukemia was established by incision biopsy in 4 patients, subsequently confirmed by peripheral blood smear testing and bone marrow biopsy in 2 patients which revealed the presence of systemic involvement. Imprint smears of the biopsy identified blasts in 2 of 4 cases. In 8 patients presenting with ocular manifestations, diagnosis was established by peripheral blood smear examination alone which revealed a diagnosis of acute myeloid leukemia.</p> <p>Conclusion</p> <p>A peripheral blood smear should be performed in all cases of sudden onset proptosis or an orbital mass in children and young adults along with an orbital biopsy. It can always be complemented with a bone marrow biopsy especially in cases of aleukemic leukemia or when the blood smear is inconclusive.</p

Single-pulse chemical shock tube for ignition delay measurements

We describe a single-pulse chemical shock tube CST2 established for measuring the reaction rate of chemical reactions and ignition delay for fuels at high temperature along with the procedure for its calibration. The suitability of the facility for measuring the ignition delay is demonstrated by measuring the ignition delay for the ethane-oxygen gas mixture in the temperature range 1250-1611 K by recording the ignition-induced pressure jump and emission from CH radical simultaneously. The results obtained in the present study compare well with the earlier reported values

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Formulation, characterization and in vivo evaluation of novel edible dosage form containing nebivolol HCl

ABSTRACT The objective of this investigation was to develop a novel oral edible gel dosage form for nebivolol hydrochloride, with suitable rheological characteristics that can provide a means of administering the drug to dysphagic and geriatric patients. Edible gels were prepared using low acetylated gellan gum and sodium citrate in different concentrations. The effect of concentration of the solution on gelation time, viscosity, and drug release was studied. Optimized formulation had "spoon thick" consistency that is considered suitable for dysphagic patients as suggested by National Dysphagia Diet Task Force. The optimized formulation containing gellan gum (0.4 % w/v) and sodium citrate (0.3 % w/v) showed more than 95% drug release in 20 minutes. This formulation also showed significantly better pharmacokinetic profile when compared to marketed conventional tablets in New Zealand white rabbits (n = 3). Optimized formulation was found stable for 6 months when stored at 25 °C ± 0.2 °C/60 ± 5% RH. From this study, it can be concluded that the novel edible gel dosage form containing nebivolol hydrochloride may prove to be more efficacious in the treatment of hypertension in dysphagic patients

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Cerebral atypical teratoid rhabdoid tumour arising in a child treated for acute lymphoblastic leukaemia

Atypical teratoid rhabdoid tumours (ATRT) are rare, arising typically in childhood. ATRT arising as a secondary tumour in children treated for acute lymphoblastic leukaemia have not been reported so far. We report a case of ATRT in a 17-year-old boy, 11 years after he was treatment for acute lymphoblastic leukaemia with cranial radiation