An editor's view of telemedicine

Should an editor hold a view about telemedicine, or should an editor be entirely disinterested? The editorial role has been defined by the International Committee of Medical journal Editors and a long list of editorial responsibilities has been set out by the World Association of Medical Editors. This represents something of a counsel of perfection, although clearly an editor should not have a personal view, in the sense of promoting telemedicine or dismissing it. Since telemedicine editors are almost bound to be active in research, they should take particular care with manuscripts involving their own work, for example standing aside from the editorial process and delegating editorial decisions to other members of the editorial staff. At the beginning of the 1990s, there were few publications about telemedicine in the peer-reviewed literature. The subsequent years have seen a rapid growth in numbers of articles and the emergence of two specialist journals. These are all healthy signs. However, there have been remarkably few studies of telemedicine's cost-effectiveness, which must represent a sign of its immaturity. On balance, the evidence seems to indicate that telemedicine research is in a healthy state.

Impact numbers: measures of risk factor impact on the whole population from case-control and cohort studies

Objective: To describe new measures of risk from case-control and cohort studies, which are simple to understand and relate to numbers of the population at risk. Design: Theoretical development of new measures of risk. Setting: Review of literature and previously described measures. Main results: The new measures are: (1) the population impact number (PIN), the number of those in the whole population among whom one case is attributable to the exposure or risk factor (this is equivalent to the reciprocal of the population attributable risk),- (2) the case impact number (CIN) the number of people with the disease or outcome for whom one case will be attributable to the exposure or risk factor (this is equivalent to the reciprocal of the population attributable fraction); (3) the exposure impact number (EIN) the number of people with the exposure among whom one excess case is attributable to the exposure (this is equivalent to the reciprocal of the attributable risk); (4) the exposed cases impact number (ECIN) the number of exposed cases among whom one case is attributable to the exposure (this is equivalent to the reciprocal of the aetiological fraction). The impact number reflects the number of people in each population (the whole population, the cases, all those exposed, and the exposed cases) among whom one case is attributable to the particular risk factor. Conclusions: These new measures should help communicate the impact on a population, of estimates of risk derived from cohort or case-control studies.

Enhanced downregulation of the p75 nerve growth factor receptor by cholesteryl and bis-cholesteryl antisense oligonucleotides

The effects of conjugating cholesterol to either or both ends of a phosphorothioate (PS) oligonucleotide were analyzed in terms of cellular uptake and antisense efficacy. The oligo sequence was directed against the p75 nerve growth factor receptor (p75), and was tested in differentiated PC12 cells, which express high levels of this protein. The addition of a single cholesteryl group to the 5'-end significantly increased cellular uptake and improved p75 mRNA downregulation compared with the unmodified PS oligo, However, only a minor degree of downregulation of p75 protein was obtained with 5' cholesteryl oligos, Three different linkers was used to attach the 5' cholesteryl group but were found not to have any impact on efficacy. Addition of a single cholesteryl group to the 3'-end led to greater p75 mRNA downregulation (31%) and p75 protein downregulation (28%) than occurred with the 5' cholesteryl oligos. The biggest improvement in antisense efficacy, both at the mRNA and protein levels, was obtained from the conjugation of cholesterol to both ends of the oligo. One of the bis-cholesteryl oligos was nearly as effective as cycloheximide at decreasing synthesis of p75, The bis-cholesteryl oligos also displayed significant efficacy at 1 mu M, whereas the other oligos required 5 mu M to be effective. The enhanced efficacy of bis-cholesteryl oligos is likely to be due to a combination of enhanced cellular uptake and resistance to both 5' and 3' exonucleases.

Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: Correlations with fetal growth

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFSP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gestation (K36). The mean concentration (+/-SEM) of total PGH increased significantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P < 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-5 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGK at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P < 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P < 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r = -0.52; P

Impact of voluntary folate fortification on plasma homocysteine and serum folate in Australia from 1995 to 2001: a population based cohort study

Study objective: To investigate the effect of the voluntary folate fortification policy in Australia on serum folate and total plasma homocysteine (tHcy) concentrations. Design: Population based cohort study. Setting: Perth, Western Australia. Participants: Men and women aged 27 to 77 years (n = 468), who were originally randomly selected from the Perth electoral roll. The cohort was surveyed in 1995/96 before widespread introduction of folate fortification of a variety of foods, and followed up on two occasions, firstly in 1998/99 and again in 2001, when a moderate number of folate fortified foods were available. Subjects with abnormal serum creatinine concentrations at baseline were excluded from this analysis. Main results: Repeated measures analysis of variance was used to determine changes in serum folate and tHcy over the three surveys and to assess whether time trends were related to age, sex, MTHFR C677T genotype, or consumption of folate fortified foods. An increase (38%) in mean serum folate (p < 0.0005) and a decrease (21%) in mean tHcy (p < 0.0005) were seen after introduction of the voluntary folate fortification policy in Australia. Serum folate was consistently higher (p = 0.032) and tHcy was consistently lower (p = 0.001) in subjects who consumed at least one folate fortified food compared with subjects who did not consume any folate fortified foods in the previous week. The time related changes in serum folate and tHcy were affected only by intake of folate fortified foods (p < 0.0005) and not by any other measured variables including age, sex, or MTHFR genotype. Conclusion: Voluntary fortification of foods with folate in Australia has been followed by a substantial increase in serum folate and decrease in tHcy in the general population.

The impact of diabetes on survival among patients with first myocardial infarction

OBJECTIVE - The purpose of this paper is to estimate the impact of diabetes on survival among patients with first acute myocardial infarction, using data from the World Health Organization (WHO) Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) Project in Newcastle, New South Wales, Australia. RESEARCH DESIGN AND METHODS - The WHO MONICA Project is a community-based surveillance system that monitors coronary heart disease morbidity and mortality. All patients with suspected coronary events were observed for 28 days after the onset of symptoms. RESULTS - Of 5,322 patients with acute myocardial infarction and no previous history of ischemic heart disease (3,643 men and 1,679 women), 333 men (9%) and 224 women (13%) had a history of diabetes. The age-adjusted 28-day case fatality for women with diabetes (25%) was significantly higher than for women without diabetes (16%); relative risk 1.56 (95% CI: 1.19-2.04). The difference for men was also significant (25% with diabetes and 20% without diabetes); relative risk 1.25 (95% CI: 1.02-1.53). Age-specific case fatality increased significantly with age in both men and women without diabetes, but systematic age effects were not so apparent in patients with diabetes. Case fatality significantly decreased over the study period in patients without diabetes, but not among the diabetic patients. CONCLUSIONS - The increased risk of death in the diabetic patients remained after accounting for their poorer risk factor profiles; even if they reached the hospital alive, diabetic patients were also less likely to survive than nondiabetic patients. The relative impact of diabetes on survival is greater in women than in men.

Assessing alternative models of individualism and collectivism: A confirmatory factor analysis

Six alternative structural models of individualism-collectivism are reviewed and empirically compared in a confirmatory factor analysis of questionnaire data from an Australian student sample (N=340). Central to the debate about the structure of this broad social attitude are the issues of (I) polarity (are individualism and collectivism bipolar opposites, or orthogonal factors?) and (2) dimensionality (are individualism and collectivism themselves higher-order constructs subsuming several more specific factors and, if so, what are they?). The data from this Australian sample support a model that represents individualism and collectivism as a higher-order bipolar factor hierarchically subsuming several bipolar reference-group-specific individualisms and collectivisms. Copyright (C) 2001 John Wiley & Sons, Ltd.

Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma

MC1R gene variants have previously been associated with red hair and fair skin color, moreover skin ultraviolet sensitivity and a strong association with melanoma has been demonstrated for three variant alleles that are active in influencing pigmentation: Arg151Cys, Arg160Trp, and Asp294His. This study has confirmed these pigmentary associations with MC1R genotype in a collection of 220 individuals drawn from the Nambour community in Queensland, Australia, 111 of whom were at high risk and 109 at low risk of basal cell squamous cell carcinoma. Comparative allele frequencies for nine MC1R variants that have been reported in the Caucasian population were determined for these two groups, and an association between prevalence of basal cell carcinoma, squamous cell carcinoma, solar keratosis and the same three active MC1R variant alleles was demonstrated [odds ratio=3.15 95% CI (1.7, 5.82)]. Three other commonly occurring variant alleles: Val60Leu, Val92Met, and Arg163Gln were identified as having a minimal impact on pigmentation phenotype as well as basal cell carcinoma and squamous cell carcinoma risk. A significant heterozygote effect was demonstrated where individuals carrying a single MC1R variant allele were more likely to have fair and sun sensitive skin as well as carriage of a solar lesion when compared with those individuals with a consensus MC1R genotype. After adjusting for the effects of pigmentation on the association between MC1R variant alleles and basal cell carcinoma and squamous cell carcinoma risk, the association persisted, confirming that presence of at least one variant allele remains informative in terms of predicting risk for developing a solar-induced skin lesion beyond that information gained through observation of pigmentation phenotype.

Peritoneal cytology: impact on disease-free survival in clinical stage I endometrioid adenocarcinoma of the uterus

The prognostic significance of positive peritoneal cytology in endometrial carcinoma has led to the incorporation of peritoneal cytology into the current FIGO staging system, While cytology was shown to be prognostically relevant in patients with stage II and III disease, conflicting data exists about its significance in patients who would have been stage I but were classified as stage III solely and exclusively on the basis of positive peritoneal cytology (clinical stage I). Analysis was based on the data of 369 consecutive patients with clinical stage I endometrioid adenocarcinoma of the endometrium. Standard treatment consisted of an abdominal total hysterectomy, bilateral salpingo-oophorectomy with or without pelvic lymph node dissection. Peritoneal cytology was obtained at laparotomy by peritoneal washing of the pouch of Douglas and was considered positive if malignant cells could be detected regardless of the number of malignant cells present. Disease-free survival (DFS) was considered the primary statistical endpoint. In 13/369 (3.5%) patients, positive peritoneal cytology was found. The median follow-up was 29 months and 15 recurrences occurred. Peritoneal cytology was independent of the depth of myometrial invasion and the grade of tumour differentiation, Patients with negative washings had a DFS of 96'7e at 36 months compared with 67% for patients with positive washings (log-rank P < 0.001). The presence of positive peritoneal cytology in patients with clinically stage I endometrioid adenocarcinoma of the endometrium is considered an adverse prognostic factor. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

The impact of genotyping error on haplotype reconstruction and frequency estimation

The choice of genotyping families vs unrelated individuals is a critical factor in any large-scale linkage disequilibrium (LD) study. The use of unrelated individuals for such studies is promising, but in contrast to family designs, unrelated samples do not facilitate detection of genotyping errors, which have been shown to be of great importance for LD and linkage studies and may be even more important in genotyping collaborations across laboratories. Here we employ some of the most commonly-used analysis methods to examine the relative accuracy of haplotype estimation using families vs unrelateds in the presence of genotyping error. The results suggest that even slight amounts of genotyping error can significantly decrease haplotype frequency and reconstruction accuracy, that the ability to detect such errors in large families is essential when the number/complexity of haplotypes is high (low LD/common alleles). In contrast, in situations of low haplotype complexity (high LD and/or many rare alleles) unrelated individuals offer such a high degree of accuracy that there is little reason for less efficient family designs. Moreover, parent-child trios, which comprise the most popular family design and the most efficient in terms of the number of founder chromosomes per genotype but which contain little information for error detection, offer little or no gain over unrelated samples in nearly all cases, and thus do not seem a useful sampling compromise between unrelated individuals and large families. The implications of these results are discussed in the context of large-scale LD mapping projects such as the proposed genome-wide haplotype map.

Is discrepancy between actual and preferred work activities a factor in work-related stress for mental health occupational therapists and social workers

In the Western developed nations, the changing pattern of mental health care provision has necessitated mental health staff adopting new approaches to service delivery across a diverse and expanding range of service settings. The impact of changed service delivery on Australian mental health professionals is an area that has not been well studied. The aim of the study was to identify the current clinical work activities performed by occupational therapists and social workers and whether there was a discrepancy between the actual and preferred work activities. The study also aimed to identify whether any discrepancy between their actual and preferred clinical work activities was associated with higher levels of stress. A cross-sectional survey of 304 (response rate 76.6%) occupational therapists and social workers in Australian mental health services was conducted. A work activities scale developed specifically for this study and the Mental Health Professionals Stress Scale were used to measure actual and preferred work activities and stress respectively. Both groups experienced a discrepancy between their actual and preferred work activities, with the occupational therapists and the social workers mostly wanting to undertake a diverse range of activities to a significantly greater extent than they currently were. As predicted, stress was associated with the discrepancy between the kind of work that the participants wanted to do and the kind of work that their job actually entailed. Health workers require assistance to adapt to their new work roles and to achieve a balance between generic and discipline-specific competencies. This has implications for education and professional training.

Evaluation of the impact of natural enemies on Plutella xylostella L. (Lepidoptera: Yponomeutidae) populations on commercial Brassica farms

1 Accurate assessment of the impact of natural enemies on pest populations is fundamental to the design of robust integrated pest management programmes. In most situations, diseases, predators and parasitoids act contemporaneously on insect pest populations and the impact of individual natural enemies, or specific groups of natural enemies, is difficult to interpret. These problems are exacerbated in agro-ecosystems that are frequently disrupted by the application of insecticides. 2 A combination of life-table and natural enemy exclusion techniques was utilized to develop a method for the assessment of the impact of endemic natural enemies on Plutella xylostella populations on commercial Brassica farms. 3 At two of the experimental sites, natural enemies had no impact on P. xylostella survival, at two other sites, natural enemy impact was low but, at a fifth site, natural enemies drastically reduced the P. xylostella population. 4 The calculation of marginal death rates and associated k-values allowed the comparison of mortality factors between experimental sites, and indicated that larval disappearance was consistently the most important mortality factor, followed by egg disappearance, larval parasitism and pupal parasitism. The appropriateness of the methods and assumptions made to calculate the marginal death rates are discussed. 5 The technique represents a robust and easily repeatable method for the analysis of the activity of natural enemies of P. xylostella, which could be adapted for the study of other phytophagous pests.

Either interleukin-12 or interferon-gamma can correct the dendritic cell defect induced by transforming growth factor beta(1) in patients with myeloma

The poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44(+)) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up-regulate the expression of the B7 co-stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor beta(1) (TGFbeta(1)) and interleukin (IL)-10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti-TGFbeta(1). As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up-regulation was reduced in both stage I and stage III. It was demonstrated that both IL-12 and interferon-gamma neutralized the failure to stimulate CD80 up-regulation by huCD40LT in vitro. IL-12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123-) suggesting that there would be a predominantly T-helper cell type response. The addition of IL-12 or interferon-gamma to future immunotherapy trials involving these patients should be considered.