(11)C-Pittsburgh compound B (PIB) binding is moderately increased in most patients with probable cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage. The distribution may differ from that seen in Alzheimer disease. (11)C-PIB PET may assist in the in vivo diagnosis of CAA and serve as a surrogate marker for future therapeutic studies.
An array of cell-surface antigens expressed by human cancers have been identified as targets for antibody-based therapies. The great majority of these antibodies do not have specificity for cancer but recognize antigens expressed on a range of normal cell types (differentiation antigens). Over the past two decades, our group has analyzed thousands of mouse monoclonal antibodies for cancer specificity and identified a battery of antibodies with limited representation on normal human cells. The most tumor-specific of these antibodies is 806, an antibody that detects a unique epitope on the epidermal growth factor receptor (EGFR) that is exposed only on overexpressed, mutant, or ligand-activated forms of the receptor in cancer.
In vitro
immunohistochemical specificity analysis shows little or no detectable 806 reactivity with normal tissues, even those with high levels of wild-type (wt)EGFR expression. Preclinical studies have demonstrated that 806 specifically targets a subset of EGFR expressed on tumor cells, and has significant anti-tumor effects on human tumor xenografts, primarily through abrogation of signaling pathways. The present clinical study was designed to examine the
in vivo
specificity of a chimeric form of mAb 806 (ch806) in a tumor targeting/biodistribution/pharmacokinetic analysis in patients with diverse tumor types. ch806 showed excellent targeting of tumor sites in all patients, no evidence of normal tissue uptake, and no significant toxicity. These
in vitro
and
in vivo
characteristics of ch806 distinguish it from all other antibodies targeting EGFR.
). The first infusion of hu3S193 was trace labeled with Indium-111, and biodistribution, pharmacokinetics, tumor uptake, and immune response were evaluated in all patients. Results: A total of 15 patients (7 male/8 female; age range, 42-76 years; 6 breast, 8 colorectal cancer, and 1non^small-cell lung cancer) were entered into the study. Transient grade 1to 2 nausea and vomiting was observed following infusion of hu3S193 at the 40mg/m 2 dose level only. There was one episode of dose-limiting toxicity with self-limiting CommonToxicity Criteria grade 3 elevated alkaline phosphatase observed in one patient with extensive liver metastases. The biodistribution of 111 In-hu3S193 showed no evidence of any consistent normal tissue uptake, and 111In-hu3S193 uptake was observed in cutaneous, lymph node, and hepatic metastases. Hu3S193 displayed a long serum half-life (T 1/2 h = 189.63 F 62.17 h). Clinical responses consisted of 4 patients with stable disease and 11 patients with progressive disease, although one patient experienced a 89% decrease in a lymph node mass, and one patient experienced inflammatory symptoms in cutaneous metastases, suggestive of a biological effect of hu3S193. No immune responses (human anti-human antibody) to hu3S193 were observed. Conclusion: Hu3S193 is well tolerated and selectively targets tumors, and the long half-life and biological function in vivo of this antibody makes it an attractive potential therapy for patients with Le y -expressing cancers.
Aim
To describe sociodemographic characteristics and comorbidities of a large cohort of Australian general practice‐based patients identified as having chronic kidney disease (CKD), using data from National Prescribing Service (NPS) MedicineWise's MedicineInsight dataset, and compare this dataset to the 2011–2012 Australian Health Survey's (AHS) CKD prevalence estimates.
Methods
This was a cohort study using deidentified, longitudinal, electronic health record data collected from 329 practices and 1 483 416 patients distributed across Australia, from 1 June 2013 until 1 June 2016. Two methods were used to calculate the CKD prevalence. One used the same method as used by the 2011–2012 AHS, based on one estimate of the estimated glomerular filtration rate (eGFR) or albumin/creatinine ratios (ACR). The other defined CKD more rigorously using eGFR or ACR results at least 90 days apart.
Results
In 2016, of 1 310 602 active patients, 710 674 (54.2%) did not have an eGFR or ACR test, while 524 961 (40.1%) had an eGFR or ACR test but did not meet AHS criteria for CKD. Age–sex adjusted rates of CKD (compared to AHS) were CKD 1–0.45% (3.9%), CKD 2–0.62% (2.5%), CKD 3a: 3.1% (2.7%), CKD 3b: 1.14% (0.6%), CKD 4–5: 0.41% (0.3%). The CKD cohort defined more rigorously using eGFR and ACR measures >90 days apart, had comorbidities of atrial fibrillation (30.5%), cardiovascular disease (25.0%), diabetes mellitus (17.1%) and hypertension (14.8%).
Conclusion
The MedicineInsight dataset contains valuable and timely information about Australian patients with CKD, and provides prevalence estimates similar to those from AHS data.
Background: Chronic kidney disease (CKD) affects drug elimination and patients with CKD require appropriate adjustment of renally cleared medications to ensure safe and effective pharmacotherapy. The main objective of this study was to determine the extent of potentially inappropriate prescribing (PIP; defined as the use of a contraindicated medication or inappropriately high dose according to the kidney function) of renally-cleared medications commonly prescribed in Australian primary care, based on two measures of kidney function. A secondary aim was to assess agreement between the two measures. Methods: Retrospective analysis of routinely collected de-identified Australian general practice patient data (NPS MedicineWise MedicineInsight from January 1, 2013, to June 1, 2016; collected from 329 general practices). All adults (aged ≥18 years) with CKD presenting to general practices across Australia were included in the analysis. Patients were considered to have CKD if they had two or more estimated glomerular filtration rate (eGFR) recorded values < 60 mL/min/1.73m 2 , and/or two urinary albumin/creatinine ratios ≥3.5 mg/mmol in females (≥2.5 mg/mmol in males) at least 90 days apart. PIP was assessed for 49 commonly prescribed medications using the Cockcroft-Gault (CG) equation/eGFR as per the instructions in the Australian Medicines Handbook. Results: A total of 48,731 patients met the Kidney Health Australia (KHA) definition for CKD and had prescriptions recorded within 90 days of measuring serum creatinine (SCr)/estimated glomerular filtration rate (eGFR). Overall, 28, 729 patients were prescribed one or more of the 49 medications of interest. Approximately 35% (n = 9926) of these patients had at least one PIP based on either the Cockcroft-Gault (CG) equation or eGFR (CKD-EPI; CKD-Epidemiology Collaboration Equation). There was good agreement between CG and eGFR while determining the appropriateness of medications, with approximately 97% of the medications classified as appropriate by eGFR also being considered appropriate by the CG equation. Conclusion: This study highlights that PIP commonly occurs in primary care patients with CKD and the need for further research to understand why and how this can be minimised. The findings also show that the eGFR provides clinicians a potential alternative to the CG formula when estimating kidney function to guide drug appropriateness and dosing.
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