Incidence and predisposing factors for flucloxacillin-related hepatotoxicity in children.

BACKGROUND: Flucloxacillin-induced hepatotoxicity is well established in adults. However, there are few paediatric studies of flucloxacillin-induced hepatotoxicity despite this drug being among the most commonly prescribed in children. We aimed to determine the incidence of flucloxacillin-induced hepatotoxicity in children receiving IV therapy as well as identify risk factors for this adverse drug reaction. METHODS: We undertook a 2 year retrospective audit of children aged 0-18 years admitted to the Royal Children's Hospital (March 2019 to March 2021) who had liver function tests determined before and after receiving IV flucloxacillin for at least 24 hours duration. Causality was assessed using the Roussel Uclaf Causality Assessment Method and Naranjo criteria. RESULTS: Overall, the incidence of hepatotoxicity was 66/393 (17%). The median age of children with hepatotoxicity was 1.1 years (IQR 0.3-11.9), 43 (65%) received two or more concomitant hepatotoxic medications and 23 (35%) were receiving total parenteral nutrition. The median timing of onset of hepatotoxicity after commencement of flucloxacillin was 4 days (range 2-7). Severe hepatotoxicity (Common Terminology Criteria for Adverse Events grade 3 or above) occurred in 9/66 (14%) for bilirubin, 13/66 (20%) for ALT and 10/66 (15%) for GGT. Predisposing factors for hepatotoxicity were increasing age (OR 1.06 per additional year, 95% CI 1.01-1.10, P = 0.02), with adolescents aged 12-18 years having the highest risk (OR 5.10, 95% CI 2.02-12.85, P = 0.001), and two or more concomitant hepatotoxic medications (OR 2.51, 95% CI 1.02-6.18, P = 0.05). The median time to resolution of hepatotoxicity after cessation of flucloxacillin was 5 days (range 2-10). CONCLUSIONS: In children, older patients and those receiving two or more concomitant hepatotoxic medications are at greater risk of flucloxacillin-induced hepatotoxicity.

Hospital Teaching Status and Patient-Reported Outcomes Following Primary Total Hip Arthroplasty: An American Joint Replacement Registry Study.

INTRODUCTION: Previous studies have shown lower morbidity and mortality rates after total hip arthroplasty (THA) at academic teaching hospitals. This study sought to determine the relationship between hospital teaching status and patient-reported outcome measures following primary THA. METHODS: Using American Joint Replacement Registry data from 2012 to 2020, 4,447 primary, elective THAs with both preoperative and one year postoperative Hip disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS, JR) scores were analyzed. The main exposure variable was hospital teaching status, with three cohorts, as follows: major teaching hospitals, minor teaching hospitals, and non-teaching hospitals. Mean preoperative and one year postoperative HOOS, JR scores were compared. RESULTS: Preoperative HOOS, JR scores (nonteaching: 49.69 ± 14.42 versus major teaching: 47.68 ± 15.10 versus minor teaching: 42.46 ± 19.19, P < .001) were significantly higher at non-teaching hospitals than major and minor teaching hospitals, and these differences persisted at one year postoperatively (87.40 ± 15.14 versus 83.87 ± 16.68 versus 80.37 ± 19.27, P < .001). Both preoperative and postoperative differences in HOOS, JR scores were less than the minimum clinically important difference (MCID) at both time points. In multivariate regressions, non-teaching and minor teaching hospitals had similar odds of MCID achievement in HOOS, JR scores compared to major teaching hospitals. CONCLUSION: Using the HOOS, JR score as a validated outcome measure, undergoing primary THA at an academic teaching hospital did not correlate with higher postoperative HOOS, JR scores or greater chances of MCID achievement in HOOS, JR scores compared to non-teaching hospitals. Further work is required to determine the most important factors that may lead to improvement in patient-reported outcomes following THA.

Frequency of drug-induced liver injury in children receiving anti-staphylococcal penicillins.

INTRODUCTION: Anti-staphylococcal penicillins (ASPs) are among the most commonly prescribed antibiotics in children and are associated with a risk of drug-induced liver injury (DILI). Despite the frequent use of ASPs in children, there is no consensus on whether liver function tests (LFTs) should be routinely monitored during treatment. OBJECTIVES: To review the literature on the frequency of ASP-related DILI in children to determine the incidence, risk factors and outcomes of hepatotoxicity. METHODS: PubMed, MEDLINE and Embase were searched in January 2022 for original studies of children who received cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin or oxacillin that included ≥10 children aged up to 18 years, and presented data on the incidence of DILI in children exposed to ASPs. RESULTS: Overall, two studies of oral flucloxacillin, two of intravenous (IV) methicillin, three of IV nafcillin and four of IV oxacillin were included. The mean onset of DILI ranged between 7.0 and 19.0 days following commencement of antibiotic treatment and all episodes resolved between 14.2 and 16.0 days after drug discontinuation, with no specific treatment required. This review found that the incidence of DILI in children was 1 in 50 000 for oral flucloxacillin and ranged from 1 in 3 to 13 for IV oxacillin, methicillin and nafcillin. CONCLUSIONS: This review found that routine LFT monitoring is not required in children receiving low dose oral flucloxacillin in a primary care setting, although pharmacovigilance is critical. For IV preparations, the existing data support routine LFT monitoring in those receiving treatment for at least 7 days.

Mechanical complications after total knee arthroplasty.

INTRODUCTION: With the increasing demand for total knee arthroplasty (TKA) and the burden of revision TKA on the healthcare system, as well as the quality of life implications for patients, it is extremely important for surgeons to be able to anticipate and prevent TKA mechanical complications. Surgeons must be familiar with the different causes and mechanisms of TKA complications so that they can properly treat patients with failed TKAs and better avoid these complications. AREAS COVERED: This review addresses TKA mechanical complications and provides context for the topic. A detailed review of surgical factors, implant factors, and patient factors that contribute to mechanical complications after TKA is provided. All of the literature cited in this review was gathered from the PubMed online database using different keywords based on the section of the manuscript. EXPERT OPINION: As surgeons and engineers solve certain issues in TKA, new challenges will inevitably arise. We must continue to push forward and innovate from both a surgical technique and implant design perspective.

Posterior hip fracture dislocation from a non-contact injury while playing soccer. "A Case Report".

Case: 35-Year old male presented with acute right hip pain after a pivoting motion while playing soccer. This was a non-contact injury. Imaging revealed a posterior hip dislocation with an associated posterior wall acetabular fracture. He was treated with closed reduction of the hip followed by subsequent open reduction internal fixation of the acetabular fracture. Conclusion: Posterior hip fracture dislocations can occur in adults following low energy non-contact injuries. Successful outcomes can be achieved if they are treated in a timely fashion, but unrecognized injuries can lead to devastating consequences.

Total Knee Arthroplasty After Genicular Nerve Radiofrequency Ablation: Reduction in Prolonged Opioid Use Without Increased Postsurgical Complications.

INTRODUCTION: Genicular nerve radiofrequency ablation (GNRFA) is an increasingly used nonsurgical treatment modality for patients with advanced knee osteoarthritis. Previous studies have demonstrated this to be an effective and safe method to decrease pain and increase functionality in this patient population. The purpose of this study was to compare 2-year postoperative complication rates and rates of prolonged postoperative opioid usage between patients undergoing total knee arthroplasty (TKA) after previous GNRFA and those undergoing TKA alone. METHODS: Patients who underwent primary TKA after prior GNRFA (GNRFA-TKA) of the ipsilateral knee were identified in a national all-payer claims database from 2010 to 2019. Univariate and multivariable analyses were conducted comparing those with prior GNRFA and those without. Outcomes of interest included prolonged postoperative opioid usage, 2-year revision rates, and 90-day medical complications. Statistical analysis was conducted using R software provided by the PearlDiver Database. RESULTS: In total, 675 patients in the GNRFA-TKA cohort were compared with a control cohort of 255,351 patients. Genicular nerve radiofrequency ablation-total knee arthroplasty patientshad lower odds of prolonged opioid use postoperatively (OR: 0.478; 95%: 0.409 to 0.559; P < 0.001). No notable difference was observed in the 2-year surgical outcomes between cohorts. Patients in the GNRFA-TKA cohort had lower odds of requiring a blood transfusion and having postoperative anemia, all arrhythmias, and urinary infections compared with primary TKA control patients. CONCLUSION: Preoperative GNRFA leads to a lower rate of prolonged postoperative opioid use in patients undergoing TKA, without an increased risk of complications. Future prospective studies are needed to validate the findings of this database study.