15 research outputs found

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

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    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

    Scarcity of Agricultural Labour in Cold-Arid Ladakh: Extent, Implications, Backward Bending and Coping Mechanism

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    This paper has investigated the extent of agricultural labour shortage, its implications and combating strategies in a cold-arid eco-region of Ladakh in Jammu & Kashmir. The study has observed that the intensity of male agricultural labour has decreased and of female labour has increased in the cold-arid region of Ladakh, thereby, suggesting imparting of professionalism through extension trainings and other capacity building programmes among female labourers. Regression analysis has revealed that the extent of mechanization, literacy and income of non-agricultural workers are significant and negative determinants of labour availability, while improvement in landholding size and land productivity would significantly improve their supply to the farming sector. At the farm level, labour scarcity has been estimated at 27 per cent in fodder to 70 per cent of total labour requirement in apricot. Labour shortage, especially during critical farm activities, has negative implications on farm profitability and productivity levels. Farmers have adopted various strategies to combat labour scarcity, but an optimum strategy seems to be still absent. Out-migration of rural labour has been observed as a regular livelihood-security gesture in the villages. Higher number of labour days and in turn, higher annual income has been found in the non-farm avenues. Interaction of variables like wage rates and tourism in the Ladakh region has resulted in backward bending of labour supply in agriculture. On the basis of findings of this study, a few policy suggestions have emerged which include linking of production with marketing through value addition to engage labour for most part of the year and innovation in the form of location and farm-size specific machines to combat labour scarcity. Study has also emphasized on encouragement of micro-agricultural enterprises and labour exchange system as a viable strategy to reduce severity of labour scarcity problem

    Deterministic Parameters of Growth and Yield of Wheat (Triticum aestivum L.) as Influenced by Fractional Application of Nitrogen and Potassium

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    An experiment was conducted during the winter (rabi) seasons of 2020-21 and 2021-22 at Krishi Vigyan Kendra, Budgam- Shere Kashmir University of Agricultural Sciences and Technology, Kashmir, to evaluate the growth and yield variability of wheat as effected by split application of potassium (K) and nitrogen (N). The experiment was set up in a split-plot design replicated thrice with K splits as main plot factor and N splits as sub plot factor which resulted in 15 treatment combinations, viz. of K 30 kg/ha [K1: 100% as basal dose-(RFP); K2: 50% as basal dose + 50% at active tillering; K3: 25 % as basal dose + 75% at active tillering] and 5 treatments of N:120 kg/ha in split ratios of [N1 : 50% as basal + 25% at jointing + 25% at booting stage (RFP); N2:25% as basal dose + 75% at active tillering; N3 : 25% as basal dose +50% at active tillering + 25% at booting; N4 : 50% as basal + 50% at active tillering; N5 : 0% as basal + 75% at active tillering + 25% at booting]. The results revealed that growth parameters like dry matter accumulation, leaf area index, SPAD reading at various phenological stages and quality parameters like N content (%) of grain and straw, protein content of grain, yield and N use efficiency were significantly more with the application of K in two equal splits in the ratio of 50:50 as compared to the treatment where K was applied in one split as 100% basal dose. There was the non-significant effect of split application of K and N on days taken to different phenological stages. Increase in N content (%) of grain was 5.76 and 5.73% during the year 2020-21 and 2021-22, respectively. Average percent increase in grain yield, protein content of grain and N use efficiency (grain yield (kg)/kg N applied) with the application of K in two equal splits in the ratio of 50:50 during both the years was 12.46, 5.81 and 12.46% that was significantly higher as compared to recommended fertilizer application (K1)

    Synthesis, Physicochemical Characterization, Biological Evaluation, In Silico and Molecular Docking Studies of Pd(II) Complexes with P, S-Donor Ligands

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    One homoleptic (1) and three heteroleptic (2–4) palladium(II) complexes were synthesized and characterized by various physicochemical techniques, i.e., elemental analysis, FTIR, Raman spectroscopy, 1H, 13C, and 31P NMR. Compound 1 was also confirmed by single crystal XRD, showing a slightly distorted square planar geometry. The antibacterial results obtained via the agar-well diffusion method for compound 1 were maximum among the screen compounds. All the compounds have shown good to significant antibacterial results against the tested bacterial strains, Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus, except 2 against Klebsiella pneumonia. Similarly, the molecular docking study of compound 3 has shown the best affinity with binding energy scores of −8.6569, −6.5716, and −7.6966 kcal/mol against Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus, respectively. Compound 2 has exhibited the highest activity (3.67 µM), followed by compound 3 (4.57 µM), 1 (6.94 µM), and 4 (21.7 µM) against the DU145 human prostate cancer cell line using the sulforhodamine B (SRB) method as compared to cisplatin (>200 µM). The highest docking score was obtained for compounds 2 (−7.5148 kcal/mol) and 3 (−7.0343 kcal/mol). Compound 2 shows that the Cl atom of the compound acts as a chain side acceptor for the DR5 receptor residue Asp B218 and the pyridine ring is involved in interaction with the Tyr A50 residue via arene-H, while Compound 3 interacts with the Asp B218 residue via the Cl atom. The physicochemical parameters determined by the SwissADME webserver revealed that no blood-brain barrier (BBB) permeation is predicted for all four compounds, while gastrointestinal absorption is low for compound 1 and high for the rest of the compounds (2–4). As concluding remarks based on the obtained in vitro biological results, the evaluated compounds after in vivo studies might be a good choice for future antibiotics and anticancer agents

    Computational Investigation of 1, 3, 4 Oxadiazole Derivatives as Lead Inhibitors of VEGFR 2 in Comparison with EGFR : Density Functional Theory, Molecular Docking and Molecular Dynamics Simulation Studies

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    Vascular endothelial growth factor (VEGF) is an angiogenic factor involved in tumor growth and metastasis. Gremlin has been proposed as a novel therapeutic pathway for the treatment of renal inflammatory diseases, acting via VEGFR 2 receptor. To date, most FDA-approved tyrosine kinase (TK) inhibitors have been reported as dual inhibitors of EGFR and VEGFR 2. The aim of the present study was to find the potent and selective inhibitor of VEGFR 2 specifically for the treatment of renal cancer. Fourteen previously identified anti-inflammatory compounds i.e., 1, 3, 4 oxadiazoles derivatives by our own group were selected for their anti-cancer potential, targeting the tyrosine kinase (TK) domain of VEGFR2 and EGFR. A detailed virtual screening-based study was designed viz density functional theory (DFT) study to find the compounds stability and reactivity, molecular docking for estimating binding affinity, SeeSAR analysis and molecular dynamic simulations to confirm protein ligand complex stability and ADMET properties to find the pharmacokinetic profile of all compounds. The DFT results suggested that among all the derivatives, the 7g, 7j, and 7l were chemically reactive and stable derivatives. The optimized structures obtained from the DFTs were further selected for molecular docking, and the results suggested that 7g, 7j and 7l derivatives as the best inhibitors of VEGFR 2 with binding energy values -46.32, -48.89 and -45.01 kJ/mol. The Estimated inhibition constant (IC50) of hit compound 7j (0.009 mu M) and simulation studies of its complexes confirms its high potency and best inhibitor of VEGFR2. All the derivatives were also docked with EGFR, where they showed weak binding energies and poor interactions, important compound 7g, 7j and 7i exhibited binding energy of -31.01, -33.23 and -34.19 kJ/mol respectively. Furthermore, the anticancer potential of the derivatives was confirmed by cell viability (MTT) assay using breast cancer and cervical cancer cell lines. At the end, the results of ADMET studies confirmed these derivatives as drug like candidates. Conclusively, the current study suggested substituted oxadiazoles as the potential anticancer compounds which exhibited more selectivity towards VEGFR2 in comparison to EGFR. Therefore, the identified lead molecules can be used for the synthesis of more potent derivatives of VEGFR2, along with extensive in vitro and in vivo experiments, that can be used to treat various cancers, especially renal cancers, and to prevent angiogenesis due to aberrant expression of VEGFR2.Funding Agencies|King Saud University, Riyadh Saudi Arabia [RSP-2021/357]</p

    Rectal diclofenac reduces the risk and severity of post-ERCP pancreatitis: a prospective, randomized, double-blind controlled study.

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    Background: Pancreatitis is the most common and feared complication of endoscopic retrograde cholangiopancreatography and its frequency is generally about 1 to 10%. A number of drugs have been used to reduce the frequency of post-ERCP pancreatitis but with conflicting results. We assessed the whether the use of diclofenac administered as rectal suppository would reduce the frequency of post-ERCP pancreatitis. Methods: A total of 925 patients were randomly assigned in a double blind fashion to receive diclofenac given as rectal suppository of100mg (467 patients) or inert placebo (458 patients) 15 min before ERCP. Serum amylase levels and patient and procedure related risk factors for post-ERCP pancreatitis were prospectively evaluated for all patients. Results The overall frequency of post-ERCP pancreatitis was 3.56%, compared to placebo, diclofenac significantly reduced the frequency (5.02% vs 2.1%; p = 0.01) as well as severity of post-ERCP pancreatitis (placebo, 19 mild, 2 moderate, 2 severe; diclofenac, 9 mild, 1 moderate, 0 severe; p = 0.02). Conclusions: Prophylactic administration of rectal diclofenac reduces the frequency and severity of post-ERCP pancreatitis

    Prospective, randomized and controlled study of the efficacy of rabeprozole and placebo in the treatment of nonerosive reflux disease.

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    Background: Nonerosive reflux disease is defined as the presence of typical symptoms of gastroesophageal reflux disease in absence of visible esophageal mucosal injury at endoscopy. 24 hour ph study is needed to define the sub group. Treatment with the acid inhibitory agents is effective, proton pump inhibitors are most effective form of therapy. Clinical results to date suggest that anti-secretory therapy may be less effective in providing symptom relief for the patients nonerosive reflux disease than the patients with erosive disease. Objective: To assess prospectively effectiveness of proton pump inhibitors in nonerosive reflux disease Methods: A total of 200 patients with nonerosive reflux disease were randomized to receive placebo (98) or rabeprozole (102) for 6 months, with consultations at 3 weeks, 6 weeks, and 6 months. The primary end points were change in the severity of heart burn and regurgitation at the above mention periods. Results: Demographics of the randomized in each group were comparable except that placebo group included more males. The baseline characteristics between two groups were similar. After 6 month of treatment, reduction of visual analogue scale (VAS) of heartburn was prominent in treatment group (63% vs. 15%). At 3 weeks and six weeks, treatment group showed greater reduction of VAS for heart burn (p<0.01). Patients of the treatment group had lower frequency of heartburn (p<0.01) and regurgitation (p<0.01) at the end of the 6 month treatment. For the adverse effects, there was no difference in the both groups. Conclusions: Rabeprozole was more effective than placebo of the treatment of symptoms presented by the patients with nonerosive reflux disease, who had positive 24 hour ph study
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