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 < 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

Synthesis and DFT study of novel pyrazole, thiophene, 1,3-thiazole and 1,3,4-thiadiazole derivatives

Regioselective facile synthesis of innovative heterocycles from the reaction of 2-cyano-N-cyclohexylacetamide (3) with hydrazonoyl chloride (4) in basic condition afforded amino pyrazole derivative 6. The behavior of acetamide 3 with phenylisothiocyanate in DMF/KOH surveyed by addition of the α-halo ketones to yeild the corresponding thiophene derivative 13a, 13b, 16, 18 and 1,3-thiazoles 21. Reaction of intermediate potassium salt 9 with hydrazonoyl chloride 22a-e furnished the corresponding 1,2,4-thiadiazoles 24a-e. Density functional theory (DFT) calculations at the B3LYP and HF techniques combined with 6-31G(d) basis set to investigate the equilibrium geometry of the innovative compound pyrazoles 6 and the stability affording of HOMO/LUMO molecular orbitals

Assessment of modern irrigation versus flood irrigation on groundwater potentiality in old clayey lands

Groundwater management in semiarid and arid regions, like northern Egypt, is essential for the sustainability of scarce resources through monitoring groundwater status and sources of recharge to the aquifer. In the Qalyubia Governorate, Nile Delta, Egypt, the study examined the recharge of groundwater in lands subject to flood irrigation and compared it with water-saving irrigation methods to detect how irrigation practices influence the potentiality of groundwater. A simulation of the two irrigation techniques, flood irrigation, and water-saving irrigation, was performed. Using GMS, simulations are done to calculate the water balance in the main 8 districts of Qalyubia Governorate. In comparison to flood irrigation, it was found that water-saving irrigation has less recharge intensity, which in turn causes a lowering in groundwater levels. The decline in groundwater table ranges between 10 and 50 cm. Modern irrigation influences the potentiality of the Nile Delta aquifer, which can’t be underestimated

Synthesis of some novel pyrazolo[1,5-<i>a</i>]quinazolines and their fused derivatives

<p>New pyrazolo[1,5-<i>a</i>]quinazoline-3-carbonitriles <b>4a,b</b> were obtained via cyclocondensation of 5-amino-3-cyanomethyl-1<i>H</i>-pyrazole-4-carbonitrile (<b>1</b>) with enaminones of 1,3-cyclohexanedione derivatives <b>2a,b</b> in refluxing glacial acetic acid. Condensation of compounds <b>4a,b</b> with various aromatic aldehydes furnished the corresponding arylidene derivatives <b>6a–j</b>. On the other hand, condensation of <b>4a,b</b> with o-hydroxybenzaldehydes yielded the polyheterocyclic compounds <b>10a–h</b>. Coupling of compounds <b>4a,b</b> with aryldiazonium chlorides led to formation of 2-arylhydrazono derivatives <b>12a–h</b>. Also, reaction of compounds <b>4a,b</b> with phenyl isothiocyanate, followed by addition of ethyl chloroacetate and chloroacetonitrile, afforded the polyheterocyclic compounds based on pyrazolo[1,5-<i>a</i>]quinazoline core. The reaction of compounds <b>4a,b</b> with phenyl isothiocyanate and elemental sulfur gave the thiazole-2-thione derivatives <b>25a,b</b>. The reaction of enamines of compounds <b>4a,b</b> with each of hydrazine hydrate and guanidine hydrochloride afforded pyrazolo[4″,3″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-<i>a</i>]quinazolin-8-ones <b>30a,b</b> and pyrimido[5″,4″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-<i>a</i>]quinazolin-9(10H)-ones <b>33a,b</b>, respectively. The structures of all the newly synthesized compounds were elucidated by elemental analyses and spectral data. The plausible mechanisms have been postulated to account for their formation.</p

Induction of ovulation in women with PCOS using letrozole versus letrozole plus gonadotropin and its effect on spontaneous on going pregnancy rate through multicenter IVF in Beni-Suef city using randomized controlled study

Background: We developed a multicenter randomized observational trial to assess the effectiveness of letrozole monotherapy and the co-therapy of letrozole and gonadotropins on pregnancy outcomes including the ovulation induction, pregnancy rate, estradiol (E2) levels and endometrial thickness in infertile women with polycystic ovarian syndrome (PCOS).Methods:At three in vitro fertilization (IVF) centers in Egypt, we conducted our study since May 2019 until we have recruited the planned number of patients. Infertile PCOS patients were recruited after they met our criteria. We had two intervention groups based on the treatment regimen.Moreover, baseline parameters, outcomes, and hormonal assessment was conducted throughout the study period.&nbsp; Results: We included 90 patients in this study and were equally randomized into two groups; the letrozole monotherapy (Group A) and the letrozole with gonadotropins (Group B) groups. The mean age was significantly higher in group A [26 (±3.5)] than group B [24.2 (±3.1)] (P= 0.015). Both groups showed resulted in similar pregnancy rates (31.1%) (P= 0.079).Moreover, group B [2.4 (±0.8)] resulted in a significantly higher (P= 0.023) mean number of follicles than group A [2.0 (±0.7)]. On the other hand, no statistical significance was estimated in terms of estradiol levels and endometrial thickness (P= 0.209 and 0.485, respectively).&nbsp

A Proposed Uncertainty Reduction Criterion of Renewable Energy Sources for Optimal Operation of Distribution Systems

Power system operation and planning studies face many challenges with increasing of renewable energy sources (RESs) penetration. These challenges revolve around the RESs uncertainty and its applications on probabilistic forecasting, power system operation optimization and power system planning. This paper proposes a novel and effective criterion for uncertainties modeling of the RESs as well as system loads. Four sorting stages are applied for the proposed uncertainty cases reduction. Added to that, it proposes three different uncertainty reduction strategies for obtaining different accuracy and speed options. The proposed reduction strategies are tested on medium and large scale distribution systems; IEEE 69-bus and 118-bus systems. The obtained results verify the effectiveness of the proposed criterion in uncertainties modeling in distribution systems with acceptable level of accuracy

Anticancer Effects with Molecular Docking Confirmation of Newly Synthesized Isatin Sulfonamide Molecular Hybrid Derivatives against Hepatic Cancer Cell Lines

The current study investigated the cytotoxic effect of ten sulfonamide-derived isatins, following molecular hybridization, based on the association principles, on hepatocellular carcinoma (HCC) HepG2 and Huh7 cell lines, compared for safety using human normal retina pigmented epithelial (RPE-1) cells. The ten compounds showed variable in vitro cytotoxicity on HepG2 and Huh7 cells, using the MTT assay. Four compounds (4/10) were highly cytotoxic to both HepG2 and HuH7. However, only 3 of these 4 were of the highest safety margin on RPE-1 cells in vitro and in the in vivo acute (14-day) oral toxicity study. These later, superior three compounds&rsquo; structures are 3-hydroxy-3-(2-oxo-2-(p-tolyl)ethyl)-5-(piperidin-1-ylsulfonyl)indolin-2-one (3a), N-(4-(2-(2-oxo-5-(piperidin-1-ylsulfonyl)indolin-3-ylidene)acetyl)phenyl)acetamide (4b), and N-(3-(2-(2-oxo-5-(piperidin-1-ylsulfonyl)indolin-3-ylidene)acetyl)phenyl)acetamide (4c). The half-maximal inhibitory concentration (IC50) of the tested compounds (3a, 4b, and 4c) on HepG2 cells were approximately 16.8, 44.7, and 39.7 &mu;M, respectively. The 3a, 4b, and 4c compounds significantly decreased the angiogenic marker epithelial growth factor receptor (EGFR) level and that was further confirmed via molecular docking inside the EFGR active site (PDB: 1M17). The binding free energies ranged between &minus;19.21 and &minus;21.74 Kcal/mol compared to Erlotinib (&minus;25.65 Kcal/mol). The most promising compounds, 3a, 4b, and 4c, showed variable anticancer potential on &ldquo;hallmarks of cancer&rdquo;, significant cytotoxicity, and apoptotic anti-angiogenic and anti-invasive effects, manifested as suppression of Bcl-2, urokinase plasminogen activation, and heparanase expression in HepG2-treated cells&rsquo; lysate, compared to non-treated HepG2 cells. In conclusion, compound &ldquo;3a&rdquo; is highly comparable to doxorubicin regarding cell cycle arrest at G2/M, the pre-G0 phases and early and late apoptosis induction and is comparable to Erlotinib regarding binding to EGFR active site. Therefore, the current study could suggest that compound &ldquo;3a&rdquo; is, hopefully, the most safe and active synthesized isatin sulfonamide derivative for HCC management

An Effective Bi-Stage Method for Renewable Energy Sources Integration into Unbalanced Distribution Systems Considering Uncertainty

The output generations of renewable energy sources (RES) depend basically on climatic conditions, which are the main reason for their uncertain nature. As a result, the performance and security of distribution systems can be significantly worsened with high RES penetration. To address these issues, an analytical study was carried out by considering different penetration strategies for RES in the radial distribution system. Moreover, a bi-stage procedure was proposed for optimal planning of RES penetration. The first stage was concerned with calculating the optimal RES locations and sites. This stage aimed to minimize the voltage variations in the distribution system. In turn, the second stage was concerned with obtaining the optimal setting of the voltage control devices to improve the voltage profile. The multi-objective cat swarm optimization (MO-CSO) algorithm was proposed to solve the bi-stages optimization problems for enhancing the distribution system performance. Furthermore, the impact of the RES penetration level and their uncertainty on a distribution system voltage were studied. The proposed method was tested on the IEEE 34-bus unbalanced distribution test system, which was analyzed using backward/forward sweep power flow for unbalanced radial distribution systems. The proposed method provided satisfactory results for increasing the penetration level of RES in unbalanced distribution networks.Peer reviewe

Optimal Harmonic Mitigation in Distribution Systems with Inverter Based Distributed Generation

In recent years, with the widespread use of non-linear loads power electronic devices associated with the penetration of various renewable energy sources, the distribution system is highly affected by harmonic distortion caused by these sources. Moreover, the inverter-based distributed generation units (DGs) (e.g., photovoltaic (PV) and wind turbine) that are integrated into the distribution systems, are considered as significant harmonic sources of severe harmful effects on the system power quality. To solve these issues, this paper proposes a harmonic mitigation method for improving the power quality problems in distribution systems. Specifically, the proposed optimal planning of the single tuned harmonic filters (STFs) in the presence of inverter-based DGs is developed by the recent Water Cycle Algorithm (WCA). The objectives of this planning problem aim to minimize the total harmonic distortion (THD), power loss, filter investment cost, and improvement of voltage profile considering different constraints to meet the IEEE 519 standard. Further, the impact of the inverter-based DGs on the system harmonics is studied. Two cases are considered to find the effect of the DGs harmonic spectrum on the system distortion and filter planning. The proposed method is tested on the IEEE 69-bus distribution system. The effectiveness of the proposed planning model is demonstrated where significant reductions in the harmonic distortion are accomplished.Peer reviewe

Antigenic evaluation of extracted fimbrial protein obtained from pathogenic Escherichia coli isolated from diarrheic camel neonates

Enteropathogenic Escherichia coli (EPEC) were considered prime reason of diarrhea among neonatal livestock animals in developing countries and could be of public health importance via contaminated milk and meat.&nbsp; Continual attempts were conducted to combat this illness using various antigenic determinants. This study was performed on four E. coli serotypes O26, O45, O103 and O111, which were previously recovered from diarrheic camel calves in Giza, Egypt. Extraction of fimbrial proteins was carried out through dialysis then evaluation of their immunogenic activity was preceded. SDS-PAGE electrophoresis was performed on crude extracted fimbrial proteins and revealed single band for each isolate ranged from 22 to 33kDa. Immunobloting was implemented on the extracted crude fimbrial proteins against E.coli O26 antisera formerly prepared in rabbit.These findings suggested that the fimbrial proteins are of immunogenicity importance and can serve as a protective passive vaccine antigen in prevention of diarrhea caused by EPEC and ETEC infection in camel calves