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

Medicinal Chemistry Strategies in Targeting TGF-βR1 Kinase Domain: Unveiling Insights into Inhibitor Structure–Activity Relationship (SAR)

The transforming growth factor-β (TGF-β) signaling pathway is involved in various cellular functions, including immunological response, extracellular matrix formation, differentiation, growth and development, and cell cycle regulation. The TGF β receptor type 1 (TGF-βR1) has emerged as a key component of this pathway, exhibiting significant overexpression in diverse malignancies, including hepatocellular carcinoma, gastric cancer, breast cancer, and colon cancer. Multiple therapeutic targets have been identified for the TGF-β signaling pathway, encompassing antibodies, ligand traps, vaccines, antisense oligonucleotides, and small-molecule TGF-βR1 kinase inhibitors. This review delineates the structural and functional characteristics of the small-molecule TGF-βR1 kinase inhibitors. The inhibitors discussed herein are categorized based on shared pharmacophoric features, notably a five-membered heterocyclic ring linked to three distinct features (R1, R2, and R3). These features interact with amino acids within the selectivity pocket, hinge region, or solvent-exposed area, respectively. These insights contribute to a clearer understanding of the structural requirements for selective TGF-βR1 inhibition. The presented findings in this review article offer a valuable foundation for future drug discovery efforts targeting the TGF-β signaling pathway

Acquired heart diseases in children in Gadarif pediatrics teaching hospital, Gadarif state, Eastern Sudan

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Acquired heart diseases (AHD) are heterogeneous diseases including rheumatic heart disease (RHD) and other affecting the heart and blood vessels after birth but usually appear clinically after 5 years of age. AHD considered as major cause of   morbidity and mortality. The present study was designed to document the spectrum, the affected age and clinical characteristics of AHDs in children of Gadarif state, eastern Sudan.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods&lt;/strong&gt;: This was a descriptive cross section study conducted in Gadarif pediatrics teaching hospital in period from June to Dec 2019.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 46 children from Gadarif pediatrics teaching hospital with confirmed AHD were enrolled in this study. The females were 27 (58.7%), with a male-to-female ratio of 1.4:1. The mean age was 10.6±3.9 years (age’s ≤16 years old); the most common affected age group was 10-14 years accounted 18 (39.1) cases. RHD was the commonest AHD found in 38 (82.6%) patients, the commonest valvular lesion was mitral regurgitation 31 (73.9%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;RHD was the most common AHD in the children in the present study, there is need to improve the scope of intervention facilities in the Sudan particularly in rural areas to prevent the growing and spread of these diseases.&lt;/p&gt;</jats:p