Clinical Activity and Quality of Life Indices Are Valid Across Ulcerative Colitis But Not Crohn’s Disease Phenotypes

Background Clinical activity and quality of life (QOL) indices assess disease activity in Crohn’s disease (CD) and ulcerative colitis (UC). However, a paucity of data exists on the validity of these indices according to disease characteristics. Aims To examine the correlation between QOL and clinical activity indices and endoscopic disease activity according to disease characteristics. Methods We used a prospective registry to identify CD and UC patients ≥18 years old with available information on Short Inflammatory Bowel Disease Questionnaire scores (SIBDQ), Harvey–Bradshaw Index (HBI) and simple endoscopic scores for CD (SES-CD), and Simple Clinical Colitis Activity Index (SCCAI) and Mayo endoscopic score for UC. We used Spearman rank correlations to calculate correlations between indices and Fisher transformation to compare correlations across disease characteristics. Results Among 282 CD patients, we observed poor correlation between clinical activity and QOL indices to SES-CD with no differences in correlation according to disease characteristics. Conversely, among 226 UC patients, clinical activity and QOL had good correlation to Mayo endoscopic score (r = 0.55 and −0.56, respectively) with better correlations observed with left-sided versus extensive colitis (r = 0.73 vs. 0.45, p = 0.005) and shorter duration of disease (r = 0.61 vs. 0.37, p = 0.04). Conclusions Our data suggest good correlation between SCCAI and endoscopic disease activity in UC, particularly in left-sided disease. Poor correlations between HBI or SIBDQ and SES-CD appear to be consistent across different disease phenotypes.American Gastroenterological Associatio

Immune system-wide Mendelian randomization and triangulation analyses support autoimmunity as a modifiable component in dementia-causing diseases

Immune system and blood–brain barrier dysfunction are implicated in the development of Alzheimer’s and other dementia-causing diseases, but their causal role remains unknown. We performed Mendelian randomization for 1,827 immune system- and blood–brain barrier-related biomarkers and identified 127 potential causal risk factors for dementia-causing diseases. Pathway analyses linked these biomarkers to amyloid-β, tau and α-synuclein pathways and to autoimmunity-related processes. A phenome-wide analysis using Mendelian randomization-based polygenic risk score in the FinnGen study (n = 339,233) for the biomarkers indicated shared genetic background for dementias and autoimmune diseases. This association was further supported by human leukocyte antigen analyses. In inverse-probability-weighted analyses that simulate randomized controlled drug trials in observational data, anti-inflammatory methotrexate treatment reduced the incidence of Alzheimer’s disease in high-risk individuals (hazard ratio compared with no treatment, 0.64, 95% confidence interval 0.49–0.88, P = 0.005). These converging results from different lines of human research suggest that autoimmunity is a modifiable component in dementia-causing diseases

Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination : A systematic review and meta-analysis

Research Funding National Health and Medical Research Council. Grant Number: APP1194679 World Health Organization Article Funding Open access publishing facilitated by The University of Sydney, as part of the Wiley - The University of Sydney agreement via the Council of Australian University Librarians.Peer reviewedPublisher PD

Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination:A systematic review and meta-analysis

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.</p

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

High fidelity numerical investigations of tailored magnetic fields for defect reduction in continuous casting of steel

In the Continuous Casting (CC) process, defects are created when the inclusions are entrained deep into the strand and are entrapped in the solidifying shell. Both the creation and entrapment of inclusions are a function of transient fluid flow behavior in the mold along with the inclusion properties. This thesis focuses on better understanding of mold flow with Electromagnetic Braking (EMBr), which is an attractive method due to its non-intrusive nature. EMBr greatly influences turbulent flow in the continuous casting mold and its transient stability, which affects level fluctuations and inclusion entrainment. Large eddy simulations are performed to investigate these transient flow phenomena using an accurate numerical scheme implemented on a Graphics Processing Unit (GPU). Two arrangements of EMBr are studied in this work, the single ruler EMBr configuration and the “Flow-Control-mold” or “FC-mold” EMBr configuration. The effects of each configuration are studied by comparing with corresponding cases without any applied magnetic field. The in-house developed CFD model is first applied to simulate experiments conducted on a 1/6th scale physical caster model with GaInSn as the low-melting conducting liquid and is then applied to the corresponding full-size caster to evaluate scaling criterion in the presence of applied magnetic fields. The mold flow has a classic “double-roll” flow pattern without the application of any magnetic fields. The application of ruler EMBr over the nozzle deflects the jets upwards and increases the top surface velocity. With insulated walls, the mold flow has large scale fluctuations and an unstable flow pattern. This instability is completely damped by using conducting side walls. These flow patterns are matched well in the corresponding real-size caster by maintaining only the Stuart number. However, to match the level fluctuations between the two casters, a Froude number ratio based scaling technique is applied. The computational model is next applied to study transient flow in a real commercial steel caster and the computed results are compared with nail board measurements. Without magnetic fields, this caster exhibits a “double-roll” flow pattern, but with transient unbalanced flow oscillations, producing unbalanced flows and vortices which might be detrimental to steel quality. The application of a FC-mold EMBr damps this unbalanced flow behavior and also reduces surface velocity, surface level fluctuations, and variations in the surface level profile. Although this might lessen slag entrainment problems, the small surface velocities resulting from this strong magnetic field across the top surface may make the meniscus prone to freezing and associated surface defects

In vitro antioxidant activity of pet ether extract of black pepper

Objective: To investigate the in vitro antioxidant activity of different fractions (R1, R2 and R3) obtained from pet ether extract of black pepper fruits (Piper nigrum   Linn.) Materials and Methods: The fractions R1, R2 and R3 were eluted from pet ether and ethyl acetate in the ratio of 6:4, 5:5 and 4:6, respectively. 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radical, superoxide anion radical, nitric oxide radical, and hydroxyl radical scavenging assays were carried out to evaluate the antioxidant potential of the extract. Results: The free radical scavenging activity of the different fractions of pet ether extract of P. nigrum (PEPN) increased in a concentration dependent manner. The R3 and R2 fraction of PEPN in 500 µg/ml inhibited the peroxidation of a linoleic acid emulsion by 60.48±3.33% and 58.89±2.51%, respectively. In DPPH free radical scavenging assay, the activity of R3 and R2 were found to be almost similar. The R3 (100µg/ml) fraction of PEPN inhibited 55.68±4.48% nitric oxide radicals generated from sodium nitroprusside, whereas curcumin in the same concentration inhibited 84.27±4.12%. Moreover, PEPN scavenged the superoxide radical generated by the Xanthine/Xanthine oxidase system. The fraction R2 and R3 in the doses of 1000µg/ml inhibited 61.04±5.11% and 63.56±4.17%, respectively. The hydroxyl radical was generated by Fenton′s reaction. The amounts of total phenolic compounds were determined and 56.98 µg pyrocatechol phenol equivalents were detected in one mg of R3. Conclusions: P. nigrum could be considered as a potential source of natural antioxidant

Fast Dissolving Tablets of Aloe Vera Gel

Purpose: The objective of this work was to prepare and evaluate fast dissolving tablets of the nutraceutical, freeze dried Aloe vera gel. Methods: Fast dissolving tablets of the nutraceutical, freeze-dried Aloe vera gel, were prepared by dry granulation method. The tablets were evaluated for crushing strength, disintegration time, wetting time, friability, drug content and drug release. A 32 full factorial design was applied to investigate the combined effect of two formulation variables -amounts of microcrystalline cellulose and mannitol. Results: The results of multiple regression analysis revealed that in order to obtain a fast dissolving tablet of the Aloe vera gel, an optimum concentration of mannitol and a higher content of microcrystalline cellulose should be used. A response surface plot was also provided to graphically represent the effect of the independent variables on the disintegration time and wetting time. The validity of the generated mathematical model was tested by preparing a check point batch. Conclusion: This investigation has demonstrated that satisfactory fast dissolving Aloe vera gel tablets can be formulated. It also showed the potential of experimental design in understanding the effect of formulation variables on the quality of fast dissolving tablets