Effect of patient age on glioblastoma perioperative treatment costs: a value driven outcome database analysis

Introduction

Identification of groups of patients or interventions with higher associated treatment costs may be beneficial in efforts to decrease the overall financial burden of glioblastoma (GBM) treatment. The authors’ objective was to evaluate perioperative surgical treatment cost differences between elderly and nonelderly patients with GBM using the Value Driven Outcome (VDO) database.

Methods

The authors obtained data from a retrospective cohort of GBM patients treated surgically (resection or biopsy) at their institution from August 2011 to February 2018. Data were compiled using medical records and the VDO database.

Results

A total of 181 patients with GBM were included. Patients were grouped into age?<?70 years at time of surgery (nonelderly; n?=?121) and?≥?70 years (elderly; n?=?60). Costs were approximately 38% higher in the elderly group on average (each patient was mean 0.68% of total cohort cost vs. 0.49%, p?=?0.044). Higher age significantly, but weakly, correlated with higher treatment cost on linear regression analysis (p?=?0.007; R²?=?0.04). Length of stay was significantly associated with increased cost on linear regression (p?<?0.001, R²?=?0.84) and was significantly longer in the elderly group (8.7?±?11.3 vs. 5.2?±?4.3 days, p?=?0.025). The cost breakdown by facility, pharmacy, supply/implants, imaging, and laboratory costs was not significantly different between age groups. Elderly patients with any postoperative complication had 2.1 times greater total costs than those without complication (p?=?0.094), 2.9 times greater total costs than nonelderly patients with complication (p?=?0.013), and 2.3 times greater total costs than nonelderly patients without complication (p?=?0.022).

Conclusions

GBM surgical treatment costs are higher in older patients, particularly those who experience postoperative complications.

     

Correlates of economic decisions in the dorsal and subgenual anterior cingulate cortices

The anterior cingulate cortex can be divided into distinct ventral (subgenual, sgACC) and dorsal (dACC), portions. The role of dACC in value‐based decision‐making is hotly debated, while the role of sgACC is poorly understood. We recorded neuronal activity in both regions in rhesus macaques performing a token‐gambling task. We find that both encode many of the same variables; including integrated offered values of gambles, primary as well as secondary reward outcomes, number of current tokens and anticipated rewards. Both regions exhibit memory traces for offer values and putative value comparison signals. Both regions use a consistent scheme to encode the value of the attended option. This result suggests that neurones do not appear to be specialized for specific offers (that is, neurones use an attentional as opposed to labelled line coding scheme). We also observed some differences between the two regions: (i) coding strengths in dACC were consistently greater than those in sgACC, (ii) neurones in sgACC responded especially to losses and in anticipation of primary rewards, while those in dACC showed more balanced responding and (iii) responses to the first offer were slightly faster in sgACC. These results indicate that sgACC and dACC have some functional overlap in economic choice, and are consistent with the idea, inspired by neuroanatomy, which sgACC may serve as input to dACC.     

Histopathological changes in the oesophageal mucosa in Egyptian children with corrosive strictures: A single-centre vast experience

BACKGROUND The caustic ingestion continues to be a major problem worldwide especially in developing countries. The long-term complications include stricture and increased life time risk of oesophageal carcinoma. Patients suffered from corrosive induced oesophageal strictures have more than a 1000-fold risk of developing carcinoma of the oesophagus.AIM To determine the possibility of oesophageal mucosal dysplasia after prolonged dilatation in post corrosive stricture.METHODS This observational study was conducted at the Paediatric Endoscopy Unit in Cairo University Children's Hospital. It included children of both sexes older than 2 years of age who had an established diagnosis of post-corrosive oesophageal stricture and repeated endoscopic dilatation sessions for more than 6 mo. All patients were biopsied at the stricture site after 6 mo of endoscopic dilatation. A histopathological examination of an oesophageal mucosal biopsy was performed for the detection of chronic oesophagitis, inflammatory cellular infiltration and dysplasia.RESULTS The mean age of the enrolled children was 5.9 ± 2.6 years; 90% of the patients had ingested an alkaline corrosive substance(potash). The total number of endoscopic dilatation sessions were ranging from 16 to 100 with mean number of sessionswas 37.2 ± 14.9. Histopathological examination of the specimens showed that 85%of patients had evidence of chronic oesophagitis(group A) in the form of basal cell hyperplasia, hyperkeratosis and subepithelial fibrosis. Thirteen percent of the patients had evidence of reactive atypia(group B) in the form of severe neutrophilic intraepithelial inflammatory cellular infiltration, and 2 patients(2%)had mild squamous dysplasia(group C); we rebiopsied these two patients 6 mo after the initial pathological assessment, guided by chromoendoscopy by Lugol's iodine.CONCLUSION The histopathology of oesophageal mucosal biopsies in post-corrosive patients demonstrates evidence of chronic oesophagitis, intraepithelial inflammatory cellular infiltration and dysplasia. Dysplasia is one of the complications of postcorrosive oesophageal stricture.     

Transurethral bipolar prostatectomy: Where do we stand now?

Transurethral resection of the prostate(TURP) is considered the gold standard surgical treatment of symptomatic benign prostatic hyperplasia. TURP has gained ground in urologic centers of excellence forits effective long term results with low incidence of complications. Far away from excellence, it associated with blood loss, and TUR syndrome particularly in patients with larger prostates. For this reasons, many minimally invasive new techniques have been implemented in recent years. Bipolar technique has recently been introduced, to minimize the complications of the standard TURP technique.     

Optical techniques for tracking multiple myeloma engraftment, growth, and response to therapy

Multiple myeloma (MM), the second most common hematological malignancy, initiates from a single site and spreads via circulation to multiple sites in the bone marrow (BM). Methods to track MM cells both in the BM and circulation would be useful for developing new therapeutic strategies to target MM cell spread. We describe the use of complementary optical techniques to track human MM cells expressing both bioluminescent and fluorescent reporters in a mouse xenograft model. Long-term tumor growth and response to therapy are monitored using bioluminescence imaging (BLI), while numbers of circulating tumor cells are detected by in-vivo flow cytometry. Intravital microscopy is used to detect early seeding of MM cells to the BM, as well as residual cancer cells that remain in the BM after the bulk of the tumor is eradicated following drug treatment. Thus, intravital microscopy provides a powerful, albeit invasive, means to study cellular processes in vivo at the very early stage of the disease process and at the very late stage of therapeutic intervention when the tumor burden is too small to be detected by other imaging methods.     

Left atrial appendage lipoma: an unusual location of cardiac lipomas

Cardiac lipomas are benign neoplasms of the heart and accounts for 8.4% of all primary tumors. They can occur sporadically at any age with no sex preference. The tumor originates mostly in the subendocardium and subepicardium but very rarely within the myocardium. Clinically this tumor is asymptomatic and found incidentally in the vast majority of cases. On occasion large lesions can lead to mechanical obstruction and pericardial effusions if located in the epicardium. Although lipomas can occur at different atrial or ventricular locations, it was never reported at the level of the left atrial appendage (LAA). Usually a mass in the LAA represents a thrombus, however there are few case reports of LAA tumors mainly representing fibroelastomas, myxomas, hemangiomas, and malignant tumors. To our knowledge there are no reported cases of left atrial appendage lipomas (LAAL) in the medical literature. We report the first case of LAAL discovered incidentally on transesophageal echocardiogram during off pump coronary artery bypass grafting.     

Role of occult hepatitis B virus in chronic hepatitis C patients with flare of liver enzymes

Background

Occult HBV infection is defined by detection of HBV DNA in the serum or liver tissue of patients who test negative for HBsAg. The prevalence of occult HBV is higher in hepatitis C virus (HCV) positive patients than HCV negative patients and may have an impact on their clinical outcome. In this study, we evaluated the role of occult hepatitis B virus infection in chronic hepatitis C patients with ALT flare.

Methods

Sixty HBsAg negative patients with chronic hepatitis C virus infection were included. Patients were divided into 2 groups according to their ALT level: 30 patients with normal or slightly high ALT and 30 patients with ALT flare (≥ 5 times normal values). Patients in both groups were examined for the detection of anti-HBs, anti-HBc IgM, and anti-HBc IgG. HBV DNA was detected using semi-nested PCR technique.

Results

In patients with normal or slightly high ALT, HBV DNA was detected in 4 (13.3%) patients, while in those with ALT flare, HBV DNA was detected in 19 (63.3%) patients (p < 0.001). No association was found between the presence of HBV DNA and various serology markers of HBV infection.

Conclusion

Presence of occult hepatitis B, with its added deleterious effect, must always be considered in chronic hepatitis C patients especially those with flare in liver enzymes; HBsAg should not be used alone for the diagnosis of HBV infection.     

Safety, tolerability, and pharmacokinetics of amuvatinib from three phase 1 clinical studies in healthy volunteers

Purpose

Amuvatinib is a multi-targeted tyrosine kinase inhibitor with activity that also disrupts DNA damage repair through suppression of homologous recombination protein Rad51. Amuvatinib dry-powder capsules (DPC) showed evidence of activity in early Phase 1 cancer studies but low systemic exposure. The purposes of the studies were to investigate the cause of low exposure, develop, and test an alternative formulation with improved exposure, and establish the dose to be tested in future studies in cancer patients.

Methods

Three studies were conducted in a total of 58 healthy subjects: a food-effect study using amuvatinib DPC, a single-dose pharmacokinetic study comparing amuvatinib DPC to a new lipid-suspension capsules (LSC), and a multiple-dose pharmacokinetic study using amuvatinib LSC.

Results

A high-fat meal administered with amuvatinib DPC increased the rate and extent of absorption compared to the Fasted state, a 183 and 118% increase in the mean C _max and AUC_0–∞ of amuvatinib, respectively. The single-dose pharmacokinetics of amuvatinib LSC resulted in an approximately two-third-fold increased exposure (AUC) compared with amuvatinib DPC. The multiple-dose pharmacokinetics of the amuvatinib LSC 300 mg administered every 8 h exhibited improved accumulation compared with the 12-h regimens and achieved presumed therapeutic level safely with no serious or severe adverse events reported. No subject discontinued treatment due to an adverse event.

Conclusion

Amuvatinib LSC, 300 mg every 8 h, is being studied in cancer patients based on the improved exposure and similar safety profile to amuvatinib DPC. A lipid-based formulation approach may be a useful tool for other low aqueous soluble compounds.     

α-Adducin gene promoter DNA methylation and the risk of essential hypertension

This study was conducted to test the association between promoter DNA methylation of α-Adducin (ADD1) gene and the risk of essential hypertension (EH). A total of 150 EH patients and 100 aged- and gender-matched controls were investigated. DNA methylation levels of five cytosine-phosphate-guanine (CpG) dinucleotides on ADD1 promoter were measured employing bisulfite pyrosequencing technology. Our results showed that females have a higher ADD1 DNA methylation than males and a significantly lower CpG1 methylation level is associated with increased risk of EH among them. As for males, a significant association between lower CpG2-5 methylation levels and increased risk of EH was shown. In addition, CpG2-5 methylation was found to be a highly significant predictor for EH among males. In females, CpG1 methylation was considered a predictor of hypertension. No significant correlations were found with biochemical measures, apart from the concentration of aspartate aminotransferase which was inversely correlated with ADD1 CpG2-5 methylation levels among female controls (r = ?0.703). These findings highlight that ADD1 methylation may have a contributing role in the pathogenesis of EH with varying implications for both genders.