Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3–13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Predictors of Chemotherapy Induced Adverse Events in Pediatric Osteosarcoma Patients

Objective: To investigate the prevalence of chemotherapy-induced adverse events and the associated risk factors in pediatric patients with osteosarcoma. Methods: This retrospective cross-sectional study enrolled 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) treated at Srinagarind Medical Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, between January 1, 2008 and December 31, 2018. The prevalence of major adverse events and a correlation between baseline characteristics and adverse events were analyzed using a generalized estimating equation model. Result: The prevalence of adverse events in 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) was determined as chemotherapy-induced nausea and vomiting (29.2%; n=296), hepatotoxicity (21.2%; n=215), anemia (70.69%; n=719), neutropenia (26.65%; n=271), and thrombocytopenia (13.65%; n=139). Factors associated with chemotherapy-induced hepatotoxicity included methotrexate dose ≥ 12 g/m2 (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.22–1.39; P<0.001), plasma concentration of methotrexate at 72 hours >0.1 μM (OR 1.22; 95% CI 1.19–1.25; P<0.001), and pre-hydration rate ≤ 125 mL/m2/h (OR 1.10; 95% CI 1.07–1.12; P<0.001). Conclusion: Major adverse events are becoming more common in pediatric osteosarcoma patients, and risk factors include larger chemotherapy doses, higher plasma methotrexate concentrations, and a slower pre-hydration rate. The outcomes of the study could aid in the better treatment of toxicity in children with osteosarcoma.     

Efficacy and safety of cold snare polypectomy for sessile serrated polyps ≥ 10 mm: A systematic review and meta-analysis

BackgroundCold snare polypectomy (CSP) is a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. However, the efficacy and safety of this technique remain undetermined.AimsWe aimed to comprehensively evaluate the efficacy and safety of CSP for SSPs ≥ 10 mm.MethodsPubMed, EMBASE, Web of Science and Cochrane Library were searched up to January 2021.ResultsA total of 10 studies consisting of 1727 SSPs (range, 10–40 mm) from 1021 patients were included. The overall rates of technical success, adverse events (AEs) and residual SSPs were 100%, 0.7% and 2.9%, respectively. Subgroup analysis showed that the rates of technical success and AEs were comparable between CSP and cold endoscopic mucosal resection (EMR) (99.9% vs. 100% and 1.3% vs. 0.5%, respectively), between the proximal and distal colon (100% vs. 99.9% and 0.3% vs. 0, respectively), and between polyps of 10–19 mm and ≥20 mm (99.8% vs. 100% and 0.9% vs. 0, respectively). However, subgroup analysis showed that the rate of residual SSPs was slightly lower in CSP compared with cold EMR (1.3% vs. 3.9%), as well as in polyps of 10–19 mm compared with those ≥20 mm (3.1% vs. 4.7%).ConclusionCSP was an effective and safe technique for removing SSPs ≥ 10 mm.     

Minimally Invasive Treatments for Benign Prostatic Hyperplasia: Systematic Review and Network Meta-Analysis

PurposeTo review and to compare indirectly the outcomes of minimally invasive therapies for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.Materials and MethodsA literature search via Medline and Cochrane Central databases was completed for randomized control studies published between January 2000 to April 2020 for the following therapies: Rezum, Urolift, Aquablation, and prostatic artery embolization (PAE). Data on the following variables were included: International prostate symptom score (IPSS), maximum urinary flow rate, quality of life, and postvoid residual (PVR). Standard mean differences between treatments were compared through a meta-analysis using transurethral resection of the prostate (TURP) to assess differences in treatment effect.ResultsThere was no significant difference in outcomes between therapies for IPSS at the 3, 6, and 12-month follow ups. Although outcomes for Rezum were only available out to 3 months, there were no consistently significant differences in outcomes when comparing Aquablation versus PAE versus Rezum. TURP PVR was significantly better than Urolift at 3, 6, and 12 months. No significant differences in minor or major adverse events were noted.ConclusionAlthough significant differences in outcomes were limited, Aquablation and PAE were the most durable at 12 months. PAE has been well studied on multiple randomized control trials with minimal adverse events while Aquablation has limited high quality data and has been associated with bleeding-related complications.     

Pharmacokinetics and Early Tumor Response to Conventional Transarterial Chemoembolization with Sorafenib and Doxorubicin in a VX2 Rabbit Tumor Model

PurposeTo investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model.Materials and MethodsVX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1α, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry.ResultsThe median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 μg/mL (interquartile range [IQR], 7.42–33.5 μg/mL), and its maximal plasma concentration (C_max) was 0.164 μg/mL (IQR, 0.0798–0.528 μg/mL). The intratumoral concentration and C_max of doxorubicin were similar between the groups: 4.08 μg/mL (IQR, 3.18–4.79 μg/mL) and 0.677 μg/mL (IQR, 0.315–1.23 μg/mL), respectively, in the DOX-TACE group and 1.68 μg/mL (IQR, 0.795–4.08 μg/mL) and 0.298 μg/mL (IQR, 0.241–0.64 μg/mL), respectively, in the SORA-DOX-TACE group. HIF-1α expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups.ConclusionsThe addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.     

The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events

Objective To explore associations between lipoprotein-associated phospholipase A2(Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up.Methods A random sample of 2,031 participants(73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study(APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay(ELISA). The composite endpoint was a combination of first-eve...     

Incidence and clinical impact of tachyarrhythmic events following transcatheter aortic valve replacement: A review

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