PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Does a high Mandard score really define a poor response to chemotherapy in oesophageal adenocarcinoma?

Background A high Mandard score implies a non-response to chemotherapy in oesophageal adenocarcinoma. However, some patients exhibit tumour volume reduction and a nodal response despite a high score. This study examines survival and recurrence patterns in these patients.Methods Clinicopathological factors were analysed using multivariable Cox regression assessing time to death and recurrence. Computed tomography-estimated tumour volume change was examined in a subgroup of consecutive patients.Results Five hundred and fifty-five patients were included. Median survival was 55 months (Mandard 1–3) and 21 months (Mandard 4 and 5). In the Mandard 4 and 5 group (332 patients), comparison between complete nodal responders and persistent nodal disease showed improved survival (90 vs 18 months), recurrence rates (locoregional 14.75 vs 28.74%, systemic 24.59 vs 48.42%) and circumferential resection margin positivity (22.95 vs 68.11%). Complete nodal response independently predicted improved survival (hazard ratio 0.34 (0.16–0.74). Post-chemotherapy tumour volume reduction was greater in patients with a complete nodal response (−16.3 vs −7.7 cm³, p = 0.033) with no significant difference between Mandard groups.Conclusion Patients with a complete nodal response to chemotherapy have significantly improved outcomes despite a poor Mandard score. High Mandard score does not correspond with a non-response to chemotherapy in all cases and patients with nodal downstaging may still benefit from adjuvant chemotherapy.Subject terms: Oesophageal cancer, Surgical oncology     

Socioeconomic determinants of health related quality of life in childhood and adolescence: results from a European study

Socioeconomic determinants of health related quality of life in childhood and adolescence: results from a European study . von Rueden , U. , Gosch , A. , Rajmil , L. , Bisegger , C. , Ravens-Sieberer , U. , the European KIDSCREEN group ( 2006 ) Journal of Epidemiology and Community Health , 60 , 130 – 135 .     

The European Menopause Survey 2005: women's perceptions on the menopause and postmenopausal hormone therapy.

OBJECTIVES: To identify and describe current women's thoughts about the menopause, hormone treatment (HT) and perceptions about breast cancer. METHODS: Between December 2004 and January 2005, 4201 postmenopausal women in seven European countries were interviewed via a standardized computer-aided telephone interview protocol. RESULTS: Almost all women reported to have experienced climacteric symptoms, and 63% of the women rated them as being severe. Only 52% of women were aware of the benefits of HT for relief of climacteric symptoms. Although 84% felt that severe symptoms should be treated, only 40% had used HT at some point in time. Thirty-four percent of the women preferring treatment with natural products did so because of the risk of breast cancer associated with HT. HT was recognized by 59% of the women as one of the most important contributors to an increased breast cancer risk. Most women received their information about HT and breast cancer risk from the media. CONCLUSIONS: This European survey reveals that the majority of women experience climacteric symptoms but that their decision whether or not to use HT is highly dependent on their concern about breast cancer risk. An increase in knowledge of the benefits and risks of HT is required for women to make appropriate decisions about hormone use.     

Human hepatocellular carcinoma tumor xenografts

Castrated or sham-operated male athymic mice were inoculated with cells from the human hepatocellular carcinoma cell line PLC/PRF/5. There were no significant differences between the two groups with respect to the number of animals developing tumors, the time to tumor development, or the subsequent rate of increase in either tumor base area or mouse serum alpha-fetoprotein concentration. Androgen receptors were assayed in nuclei obtained from three separate liver cancer cell lines and from normal adult human liver. Similar concentrations, ranging from 235 to 550 fmol/mg DNA, of nuclear androgen receptors were detected in all tissues. Low percentages of androgen receptors were retained on DNA-cellulose. Although the presence of receptors implies the potential for metabolic effects of androgens in normal and malignant liver, our in vivostudies suggest that castration does not alter significantly the growth of liver cancer xenografts in athymic mice.     

Allergy to laboratory animals: a retrospective and a prospective study.

Twenty four volunteers who had been allergic to laboratory animals for some years were examined by means of a questionnaire paying particular attention to symptoms associated with rats and by serological and skin tests with extracts of rat urine (retrospective study). Nasal and eye symptoms were reported by 21 and 16 individuals respectively: 13 had asthma. Positive skin tests and high levels of specific IgE antibody to rat urine extract were found in 17 of the more severely affected individuals and this group included 12 of those with asthma. Latent periods of work with animals before symptoms appeared varied from 0.5 to 12 years. Also 148 individuals were studied during their first year of work with animals (prospective study). Symptoms developing during the year were reported by 15%, asthma by 2%. IgE antibody levels to rat urine were raised in 40% of affected and 6% of the unaffected individuals but there was no significant correlation between symptoms and either antibody levels or positive skin tests. Allergic symptoms developing during the first year of postemployment were, on the whole, much milder than those seen in the retrospective study. A tentative conclusion is that most individuals who become allergic to laboratory animals develop the condition in a mild form during their first year of employment but it appears probable that atopic individuals, although having an equal chance of developing allergy as compared with non-atopic individuals, may eventually progress to a more severe form of the disease.     

Drug driving from a user's perspective

The bulk of research into drug driving in Australia has been undertaken from a road safety orientation where drug driving is viewed within the broader context of road safety and driver behaviour. Such a specific focus precludes the broader behavioural, contextual and cultural issues associated with substance use. This study aimed to address this issue by focusing on drug driving behaviour within the context of illicit substance use. A series of focused interviews were conducted with 211 illicit drug users from urban and regional centres. A consistent theme identified in the interviews was that drug driving was not necessarily viewed as risky behaviour but rather as an outcome of illicit substance use. Further, some interviewees saw their drug use as enhancing their driving skills and frequently the motor vehicle was viewed as a safe place to use. Overall there was agreement among interviewees that the likelihood of being apprehended for drug driving by police was minimal; this perception was reinforced by past experience. The lack of concern for detection of drug driving behaviour suggests that research should continue into the development and implementation of enforcement programs and roadside detection.     

Growth of children from 0-5 years: with special reference to mother's smoking in pregnancy

A cohort of 1163 pregnant women in two small towns in South Wales, UK, was identified and followed until the children born to them were five years of age. Growth in these children is described and a number of determinants identified. Social-class differences were very small at birth but differences in height became clear by the age of two years and in head circumference before this. In height the differences were largely accounted for by greater growth in social class I, but there was a gradient in head circumference throughout all the social classes. The social class effects gradually increased as the children became older. Parity of the mothers had a small effect on size at birth but age of the mother had no effect once parity was allowed for. Data on illnesses in the children were collected but no effect on growth could be detected. By far the most important determinant of growth which could be controlled is maternal smoking. About 40% of the women smoked, about 17% heavily (15 or more cigarettes per day) and the prevalence of smoking altered little during pregnancy. There was a graded effect of smoking on growth up to a 9% deficit in birth-weight, a 2% deficit in length at birth and a 1.5% deficit in head circumference in the babies born to the mothers who smoked most heavily (25 or more cigarettes per day) compared with non-smokers. There effects decreased with age but there were still residual effects at age five years.     

Changes in the biophysical properties and ultrastructure of lungs, and intrapulmonary fibrin deposition in experimental acute pancreatitis

Using an experimental model of acute pancreatitis in the rat, we have studied changes in the biophysical properties of lungs and intrapulmonary fibrin deposition in this condition. Acute pancreatitis is associated with a significant decrease in pulmonary compliance (p less than 0.01) and a significant increase in lung weight (p less than 0.01) compared with a control sham operation group. These changes are associated with a 24% increase in intrapulmonary 125I fibrinogen deposition (p less than 0.01), and an 18% increase in 125I fibrinogen deposition per gram of lung tissue (p less than 0.05) in acute pancreatitis, compared with a control sham operation group. The increased fibrinogen deposition is abolished by treatment with low dose heparin. Using the same animal model changes in pulmonary ultrastructure are shown using scanning electron microscopy. The results indicate that pulmonary abnormalities are associated with intrapulmonary fibrin deposition in experimental acute pancreatitis and these findings may be relevant to the well described respiratory complications of the condition in man.