Factors influencing routine cognitive impairment screening in older at-risk drinkers: Findings from a qualitative study in the United Kingdom

Cognitive Impairment (CI) screening is recommended for those engaged in harmful levels of alcohol use. However, there is a lack of evidence on implementation. This paper explores the barriers and facilitators to CI screening experienced across a service specifically for older drinkers. The findings draw on data gathered as part of an evaluation of a multilevel programme to reduce alcohol-related harm in adults aged 50 and over in five demonstration areas across the United Kingdom. It is based on qualitative interviews and focus groups with 14 service providers and 22 service users. Findings are presented thematically under the section headings: acceptability of screening, interpretation and making sense of screening and treatment options. It is suggested that engagement with CI screening is most likely when its fit with agency culture and its purpose is clear; where service providers have the technical skills to administer and discuss the results of screening with service users; and where those undertaking screening have had the opportunity to reflect on their own experience of being screened. Engagement with CI screening is also most likely where specific intervention pathways and engagement practices can be accessed to respond to assessed need.     

Pharmacokinetics and pharmacodynamics of prolonged oral etoposide in women with metastatic breast cancer

The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0–24 h) 1.95±0.87 mg/ml per min (mean ± SD), apparent oral clearance 60.9±21.7 ml/min per 1.73 m², peak plasma concentration 5.6±2.5 g/ml, time to peak concentration 73±35 min and half-life 220±83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal E_max equation. A good fit was found between day 1 AUC and neutrophil toxicity (R ²=0.77). All patients who had a day 1 AUC>2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m²). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R ²=98.9%). The equation AUC_pr=–0.376+0.631×C_4h+0.336×C_6h was validated on the test set with a relative mean predictive error of –0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett St, Melbourne 3000, Australia     

Detection of hepatic tumor perfusion following transcatheter arterial chemoembolization with dynamic susceptibility contrast-enhanced echoplanar imaging

The aim of the study was to evaluate the usefulness of the magnetic resonance (MR) perfusion maps in the detection of liver tumor perfusion following transcatheter arterial chemoembolization (TACE). MR dynamic susceptibility contrast-enhanced imaging was performed in 12 patients with 10 confirmed hepatocellular carcinoma and 2 confirmed hepatic metastasis using single-shot echoplanar pulse sequence. Time-intensity curves for all hepatic tumors showed a transient signal drop and the hepatic blood volume (HBV) maps were reconstructed. On the HBV maps, most tumors (80%) demonstrated hyperperfusion before TACE and hypoperfusion following TACE. The site and the degree of residual hyperperfusion within the tumor on the HBV maps correlated well with the areas of hypervascularity on the angiograms. In conclusion, the MR perfusion maps can be a promising technique for detecting the perfusion of the residual tumor tissue following TACE.     

Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91. Received: 7 January 1999 / Accepted: 18 May 1999     

Use of the lectin from Amaranthus caudatus as a histochemical probe of proliferating colonic epithelial cells

A newly isolated lectin, Amaranthus caudatus agglutinin (also called amaranthin or ACA), which binds to the Thomsen-Friedenreich antigen (T-antigen) and its sialylated variants, was used as a histochemical probe for proliferating cells in sections of human colonic tissues. Binding inhibition studies revealed that ACA binds to different sites on histological sections when compared to peanut agglutinin, which also recognizes the T-antigen. ACA bound selectively to the cells at the base of the colonic crypt [46 +/- 4% (SEM) of glands] which is the zone of proliferation in this tissue and preferentially labeled cytoplasmic and apical membrane glycoconjugates. Only 7 +/- 2% of the upper portions of the colonic crypts were labeled (P less than 0.001 compared to the base), and this was largely a result of extensive labeling in 2 of 23 samples studies. A marked increase in histochemical labeling by ACA was seen in adenomatous polyps and adenocarcinomas of the colon, in which 82 +/- 7 and 97 +/- 2% of the glandular units were labeled, respectively. Transitional mucosa and connective tissue adjacent to cancers were also labeled by ACA. Neuraminidase studies indicated that removal of sialic acid residues enhanced binding by peanut agglutinin, but not ACA, to glycoconjugates in cancer specimens. Specimens of colonic tissue from patients with familial adenomatous polyposis (FAP) were examined with ACA; 83 +/- 7% of adenomatous glands and 60 +/- 7% of glands in flat, normal-appearing tissue were labeled. Colonic tissues from persons at 50% risk for hereditary nonpolyposis colorectal cancer (HNPCC), FAP, and normal colons were studied and given "weighted average" labelling scores that ranged from 0-400 to accommodate variable intensity and distribution of labeling. Normal colons had a weighted average score of 65 +/- 33; FAP tissues had a score of 224 +/- 76 (P less than 0.001 compared to normal colon) and HNPCC tissues had a score of 74 +/- 70 (P less than 0.05 compared to normal colon). A group of five HNPCC cases had scores of 203 +/- 43 (P less than 0.001 compared to normal colon). ACA labels glycoconjugates in the proliferative region of normal human colonic epithelium and neoplastic lesions of the colon. The results of FAP and HNPCC tissues suggest that it may be useful for identifying foci of abnormal proliferation in familial colorectal cancer syndromes.