Drug Prices and Value of Oncology Drugs in Italy

ObjectiveThe main objective of this study was to evaluate the potential role of efficacy data and other information available at the time of price and reimbursement (P&R) decision-making process within the definition of oncology treatment costs in Italy.MethodsThe study included all P&R dossiers submitted to the Italian Medicines Agency between July 2015 and December 2017. It prospectively collected the data of the P&R process starting from dossier submission up to the Italian Health Service reimbursement decision. The cost of treatment per patient was estimated using both the list price (“gross cost”) and the confidential net price (“net cost”) of drug packages and applied to the median duration of treatment. A 2-sample stage Heckman decomposition model was used to evaluate the potential role of efficacy data and other information available at the time of P&R decision making on the gross and net cost.ResultsA total of 37 oncology drugs related to 58 therapeutic indications were analyzed. The multivariate model showed that the variation of progression-free survival is the only variable predictor statistically associated with treatment cost, but this effect was observed only when confidential net prices were used (P=.026).ConclusionsConsidering the perspective of a developed country having a public healthcare service with a central reimbursement negotiation is determined a relevant reduction in the treatment cost purchased by public payers. This is a useful approach to guarantee the affordability of innovative oncology drugs and to contain public expenditures on healthcare. Furthermore, the negotiation of confidential discounts and agreement clauses in managed entry agreements seemed to reward oncology drugs displaying an added therapeutic benefit.     

Surveillance of COVID-19–Associated Multisystem Inflammatory Syndrome in Children,South Korea

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.     

Outcomes and factors associated with early mortality in pediatric postcardiotomy veno‐arterial extracorporeal membrane oxygenation

Mortality and morbidity of children received veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) support after cardiac surgery remain high despite remarkable advances in medical management and devices. The purpose of this study was to describe outcomes and risk factors of applying VA‐ECMO in the surgical pediatric population. We retrospectively analyzed 85 consecutive pediatric patients (aged <18 years) who received postcardiotomy VA‐ECMO from January 2010 to December 2018. Median (IQR) age at ECMO implantation in this cohort was 12.7 (6.4, 43.2) months, median weight was 8.5 (6.0, 12.8) kg, mean ECMO duration was 143.2 ± 81.6 hours and mean hospital length of stay was 48.4 ± 32.4 days. Seventy‐five patients (88.2%) were indicated for postcardiotomy cardiogenic shock. The successful ECMO weaning rate was 70.6% and in‐hospital mortality was 52.9%. The most common diagnosis was transposition of great arteries (n = 18, 21.2%), while acute kidney injury occurred most often (n = 64, 75.3%). Multivariate logistic regression analysis showed that thrombocytopenia, hemolysis, and nosocomial infection were positively correlated with in‐hospital mortality. Multivariate Cox proportional hazard regression analysis presented that thrombocytopenia significantly increased the 180‐day mortality in patients with successful weaning. Therefore, multiple factors had adverse effects on prognosis. Patient selection and procedures from ECMO implantation to weaning need to be closely monitored and performed in a timely manner to improve outcome.     

A novel approach to delivery of extracorporeal support using a modified continuous flow ventricular assist device in a mid‐volume congenital heart program

Extracorporeal life support (ECLS) is an essential component of a modern congenital cardiac surgery program. The circuit components and bedside management team may, however, vary among institutions. Here, we evaluate our initial experience with a modified ventricular assist device—based ECLS circuit primarily managed by the bedside nurse. We hypothesize that our outcomes are comparable to Extracorporeal Life Support Organization (ELSO) registry data. All patients who received ECLS from January 1, 2016 to December 31, 2019 at a single institution were included. Primary outcomes were survival to ECLS decannulation and discharge or transfer. Secondary outcomes included complications from ECLS. Data were compared to available ELSO registry data. Thirty‐seven patients underwent 44 ECLS runs during the study period. Forty percent of patients had single ventricle physiology. Nearly 46% of patients received ECLS as part of extracorporeal cardiopulmonary resuscitation (eCPR). Survival to ECLS decannulation (68.2%) and survival to discharge or transfer (61.4%) did not differ from overall ELSO outcomes (69.7%, P = .870 and 50.7%, P = .136), as well as survival to discharge or transfer in a comparable cohort of ELSO centers (53.1%, P = .081). Patients with complications had a lower rate of survival to discharge or transfer but this did not reach statistical significance (47.7% vs. 75.0%, P = .455). Neurologic (50.0%), hemorrhagic (45.5%), and renal complications (31.8%) were most common in this cohort. A modified ventricular assist device‐based ECLS circuit with primary management by the bedside nurse can provide comparable support in a neonatal and pediatric cardiac surgery population. Cost analyses and further delineation of the complication profile are necessary for a complete characterization of this system.     

Risks and Complications After Arthroplasty for Pathological or Impending Pathological Fracture of the Hip

BackgroundTreatment options for metastatic osseous lesions of the proximal femur include hemiarthroplasty (HA) or total hip arthroplasty (THA) depending on lesion characteristics and patient demographics. Studies assessing short-term outcomes after HA/THA in this patient population are limited. Therefore, the purpose of this present study was to identify short-term rates of morbidity and mortality after HA/THA for pathological proximal femur fractures, as well as readmission and reoperation rates and reasons.MethodsThis study utilized a large, prospectively collected registry to identify patients who underwent HA/THA between 2011 and 2018. Patients were stratified by indication for surgery, including pathological fracture, nonpathological fracture, and osteoarthritis. Baseline patient characteristics and postoperative complications were compared using bivariate and/or multivariate analysis.ResultsIn total, 883 patients undergoing HA/THA for a pathological fracture were identified. Relative to an osteoarthritis cohort, these patients tended to be older, had a lower body mass index, and had significantly more preoperative comorbidities. These patients had high rates of total complications (13.93%), including thirty-day mortality (3.29%), unplanned return to the operating room (4.98%), and pulmonary complications (3.85%). Patients with pathological fracture had a longer operative duration relative to osteoarthritis and nonpathological cohorts (+27 and +25 minutes, respectively), despite having high rates of HAs performed.ConclusionPatients undergoing hip arthroplasty for pathologic proximal femur fracture have increased morbidity and mortality relative to an osteoarthritis cohort. However, patients with a pathological fracture have similar rates of morbidity and mortality when compared with a nonpathological fracture cohort, but did experience higher rates of perioperative blood transfusion and unplanned readmissions.Level of EvidenceIII.     

Combined breast conservation therapy versus mastectomy for BRCA mutation carriers – A systematic review and meta-analysis

BackgroundThe non-inferiority of combined breast conservation surgery (BCS) and radiotherapy (breast conservation therapy or BCT) compared to mastectomy in sporadic breast cancer cases is well recognised. Uncertainty remains regarding optimal surgical practice in BRCA mutation carriers.AimsTo evaluate the oncological safety of combined BCT versus mastectomy in BRCA mutation carriers following breast cancer diagnosis.MethodsA systematic review was performed as per PRISMA and MOOSE guidelines. Observational studies comparing BCS and mastectomy in BRCA carriers were identified. Dichotomous variables were pooled as odds ratios (OR) using the Mantel–Haenszel method. Log hazard ratios (lnHR) for locoregional recurrence (LRR), contralateral breast cancer, disease-free and overall survival and their standard errors were calculated from Kaplan-Meier or cox-regression analyses and pooled using the inverse variance method.ResultsTwenty three studies of 3807 patients met inclusion criteria; 2200 (57.7%) were BRCA1 and 1212 (31.8%) were BRCA2 carriers. Median age at diagnosis was 41 years with 96 months follow up. BCS was performed on 2157 (56.7%) while 1408 (41.5%) underwent mastectomy. An increased risk of LRR was observed in patients treated with BCS (HR:4.54, 95% Confidence Interval: 2.77–7.42, P < 0.001, heterogeneity (I²) = 0%). However, the risks of contralateral breast cancer (HR:1.51, 95%CI: 0.44–5.11, P = 0.510, I² = 80%), disease recurrence (HR:1.16, 95%CI: 0.78–1.72, P = 0.470, I² = 44%), disease-specific recurrence (HR:1.58, 95%CI: 0.79–3.15, P = 0.200, I² = 38%) and death (HR:1.10, 95%CI: 0.72–1.69, P = 0.660, I² = 38%) were equivalent for combined BCT and mastectomy.ConclusionsSurvival outcomes following combined BCT is comparable to mastectomy in BRCA carriers. However, the risk of LRR is increased. Patient counselling should be tailored to incorporate these findings.     

基于“药辅合一”理念的Pickering乳技术提升儿科用药羚珠散中石菖蒲挥发油热稳定性的研究

目的 在“药辅合一”理念下导入Pickering乳技术,提升儿科用药羚珠散中石菖蒲挥发油的稳定性。方法 对羚珠散各饮片粉末进行初步表征,确定稳定剂。通过成乳量、包油量和乳剂形态筛选出最佳稳定剂质量浓度、油水比和制备方法。并使用近红外光谱（nearinfraredspectroscopy,NIRS）分析石菖蒲油在Pickering乳中的包裹状态。比较不同时间下各组别挥发油的保有量、丙二醛和过氧化物的含量。再通过GC-MS分析其中成分的变化趋势。结果 筛选出珍珠粉作为Pickering乳的稳定剂,珍珠粉质量浓度为65 mg/mL,油水比9∶11为最优成乳条件,高压均质法为最优的制备方法,NIRS分析可知石菖蒲挥发油被珍珠粉包裹,Pickering乳液中没有形成新的化学键。对比各组在不同时间段下石菖蒲油的保有率和其中丙二醛和过氧化物含量,可知40℃放置1、3、8 h的Pickering乳剂相比于石菖蒲挥发油组有更高的保有率和更低的氧化程度。GC-MS分析结果表明,相比于石菖蒲挥发油组,Pickering乳组挥发性成分的稳定性显著提高。结论 在“药辅合一”理念下Pickering乳可用于含油固...     

Successful kidney transplantation in a patient with pre-existing chronic myeloid leukemia treated with imatinib

Active malignancy is an absolute contraindication to kidney transplantation. As for chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal into a manageable chronic disease with a close-to-normal life expectancy. To date it is unknown whether kidney transplantation can be safely performed in patients with pre-existing CML. We describe the clinical course of a 57-year-old male patient with chronic kidney disease caused by reflux nephropathy. This patient had undergone first kidney transplantation 20 years earlier and had again been on chronic hemodialysis for 6 years when CML was diagnosed. First-line therapy with 400 mg imatinib daily was well tolerated and induced an optimal cytogenetic and molecular response 3 months after initiation. One and a half years after CML diagnosis, a second kidney transplantation from a deceased donor was performed. Immunosuppression included basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids. Currently, 2 years posttransplant, renal allograft function is stable (serum creatinine 1.09 mg/dL, estimated glomerular filtration rate 75 mL/min per 1.73 m²), and CML remains in deep molecular remission with imatinib. Imatinib-treated CML in deep molecular remission could be regarded as inactive malignancy and may therefore not be viewed as an absolute contraindication to kidney transplantation.