Worst itch numerical rating scale for prurigo nodularis: a psychometric evaluation.

BACKGROUND: Study TR03 evaluated the safety and efficacy of nalbuphine ER for prurigo nodularis (PN; NCT02174419). OBJECTIVE: We conducted supplementary analyses to assess the psychometric properties of the Worst Itch Numeric Rating Scale (WI-NRS), the TR03 primary endpoint. METHODS: Study TR03 was a double-blind, placebo-controlled, phase 2 trial in PN patients with documented scores ≥5 on the WI-NRS (0 [no itch]-10 [worst itch imaginable]) on ≥5 of 7 days before baseline. Using TR03 data, the WI-NRS's psychometric properties, including reliability, validity and ability to detect change, were evaluated. A responder threshold was estimated to facilitate interpretation of WI-NRS score changes. RESULTS: Amongst 62 treated patients, improvements in mean [SD] (median) WI-NRS scores were observed between baseline (8.2 [1.21] (8.1)) and week 10 (5.8 [2.43] (6.0)). The WI-NRS had an intraclass correlation coefficient of 0.96 (95% confidence interval, 0.93-0.98) in 42 patients who had stable Itch verbal rating scale (VRS) scores from week 9-10, supporting strong test-retest reliability. Construct validity was supported, with strong correlations at week 10 with Average Itch NRS (r = 0.87) and Itch VRS single-day/weekly mean scores (r = 0.81/0.89) and moderate correlations with ItchyQoL™ total/domain scores (r = 0.41-0.43). The WI-NRS discriminated between predefined severity subgroups based on the Itch VRS and detected changes in itching severity (effect-size estimate: -2.05; standardized response mean: -1.21). An anchor-based threshold based on a two-category improvement in the single-day Itch VRS suggests a responder threshold of ≥3.8 points (~40% improvement). CONCLUSIONS: The WI-NRS demonstrates good measurement properties, supporting its use in evaluating treatment change in PN.

Establishing Clinically Meaningful Change on Outcome Assessments Frequently Used in Trials of Mild Cognitive Impairment Due to Alzheimer's Disease.

BACKGROUND: Consensus is lacking on what constitutes a meaningful score change for individual patients on clinical outcome assessments (COAs) that are commonly used in clinical trials of Alzheimer's disease. Such thresholds are one important approach to help contextualize trial results and demonstrate meaningful treatment benefit. OBJECTIVES: To estimate meaningful within-patient change thresholds for the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog), and the Mini-Mental State Examination (MMSE) among participants with mild cognitive impairment (MCI). DESIGN: Retrospective anchor- and distribution-based analyses of data from the ADC-008 (NCT00000173) study were used to estimate thresholds for meaningful within-patient change on the target measures. SETTING: Analyses were conducted using data from ADC-008 a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study among participants with the amnestic subtype of MCI, which was conducted by the Alzheimer's Disease Cooperative Study (ADCS) between March 1999 and January 2004 in the United States and Canada. PARTICIPANTS: Analyses were based on 769 eligible participants who completed the baseline assessment from 69 ADCS sites in the United States and Canada. MEASUREMENTS: The target outcome measures for this analysis included the CDR-SB, the ADAS-Cog, and the MMSE. The anchor measures for this analysis included the Global Deterioration Scale and the MCI-Clinical Global Impression of Change. RESULTS: Focusing on the 12-month time point, within-patient increases of 1-2.5 points in the CDR-SB and increases of 2-5 points on the 11-item ADAS-Cog and 13-item ADAS-Cog, on average, reflect minimal-to-moderate levels of deterioration, respectively. CONCLUSIONS: These thresholds may be useful to aid the interpretation of Alzheimer's disease clinical trial data by illustrating meaningful within-patient progression over the course of a clinical trial via supplementary progressor analyses, which may in turn be informative for treatment decisions. Estimates generated via these methods are specifically intended to evaluate within-patient change and are not intended to assess the magnitude and meaningfulness of differences between group-level changes over time.

An investigation of cancer incidence in a First Nations community in Alberta, Canada, 1995-2006.

OBJECTIVE: To determine colorectal and overall cancer incidence as part of a three-pronged investigation in response to the concerns of a First Nations community in Alberta, Canada, located close to sulfur-rich natural gas installations, and to determine whether the incidence of cancers observed in this reserve was higher than expected. METHODS: A population dataset with information identifying First Nations status and band affiliation was linked to the Alberta Cancer Registry to determine cancer incidence cases between 1995 and 2006 for on- and off-reserve study populations. Using indirect standardized incidence ratios, observed cancer incidence cases for the study populations were compared with cases expected based on three separate reference populations. RESULTS: Observed colorectal and overall cancer incidence cases within the First Nations community were not higher than expected. Cervical cancer incidence cases, however, were higher than expected for on- and off-reserve populations; public health measures designed to address this risk have been implemented and on-going surveillance of cancer incidence in the community will be maintained.

Blockade of the IL-6 trans-signalling/STAT3 axis suppresses cachexia in Kras-induced lung adenocarcinoma.

Lung cancer is the leading cause of cancer death worldwide, and is frequently associated with the devastating paraneoplastic syndrome of cachexia. The potent immunomodulatory cytokine interleukin (IL)-6 has been linked with the development of lung cancer as well as cachexia; however, the mechanisms by which IL-6 promotes muscle wasting in lung cancer cachexia are ill-defined. In this study, we report that the gp130F/F knock-in mouse model displaying hyperactivation of the latent transcription factor STAT3 via the common IL-6 cytokine family signalling receptor, gp130, develops cachexia during Kras-driven lung carcinogenesis. Specifically, exacerbated weight loss, early mortality and reduced muscle and adipose tissue mass were features of the gp130F/F:KrasG12D model, but not parental KrasG12D mice in which STAT3 was not hyperactivated. Gene expression profiling of muscle tissue in cachectic gp130F/F:KrasG12D mice revealed the upregulation of IL-6 and STAT3-target genes compared with KrasG12D muscle tissue. These cachectic features of gp130F/F:KrasG12D mice were abrogated upon the genetic normalization of STAT3 activation or ablation of IL-6 in gp130F/F:KrasG12D:Stat3-/+ or gp130F/F:KrasG12D:Il6-/- mice, respectively. Furthermore, protein levels of the soluble IL-6 receptor (sIL-6R), which is the central facilitator of IL-6 trans-signalling, were elevated in cachectic muscle from gp130F/F:KrasG12D mice, and the specific blockade of IL-6 trans-signalling, but not classical signalling, with an anti-IL-6R antibody ameliorated cachexia-related characteristics in gp130F/F:KrasG12D mice. Collectively, these preclinical findings identify trans-signalling via STAT3 as the signalling modality by which IL-6 promotes muscle wasting in lung cancer cachexia, and therefore support the clinical evaluation of the IL-6 trans-signalling/STAT3 axis as a therapeutic target in advanced lung cancer patients presenting with cachexia.

The role of organisational support in teleworker wellbeing: a socio-technical systems approach.

The prevalence of telework and other forms of mobile working enabled by digital technology is increasing markedly. Following a socio-technical systems approach, this study aims to examine the role of organisational social support and specific support for teleworkers in influencing teleworker wellbeing, the mediating role of social isolation, potentially resulting from a person-environment mismatch in these relationships, and possible differences in these relationships between low-intensity and hybrid teleworkers. Teleworkers' (n = 804) perceptions of support and telework outcomes (psychological strain, job satisfaction, and social isolation) were collected using an on-line survey of teleworking employees distributed within 28 New Zealand organisations where knowledge work was undertaken. Organisational social support and teleworker support was associated with increased job satisfaction and reduced psychological strain. Social isolation mediated the relationship between organisational social support and the two outcome variables, and some differences were observed in the structural relationships for hybrid and low-intensity teleworker sub-samples. These findings suggest that providing the necessary organisational and teleworker support is important for enhancing the teleworker-environment fit and thereby ensuring desirable telework outcomes.

Lipid peroxidation and phospholipase A2 activity in liposomes composed of unsaturated phospholipids: a structural basis for enzyme activation.

The effect of lipid peroxidation on membrane structure and phospholipase A2 activity was studied using liposomes composed of bovine liver phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The phospholipids were mixed at set ratios and sonicated to yield small unilamellar vesicles. The liposome preparations were subjected to lipid peroxidation as induced by cumene hydroperoxide and hematin. Under these conditions, a sharp increase in lipid peroxidation was noted over a 30 min incubation period and was accompanied by loss of polyunsaturated fatty acids (PUFA). Liposomes enriched in PE were most extensively peroxidized with a preferred oxidation of this phospholipid. The extent of PC oxidation was also greater in liposomes containing the largest proportions of PE. Analysis of liposome anisotropy, via steady-state fluorescence polarization of diphenylhexatriene indicated that progressive increases in either PE content or the level of lipid peroxidation increased the apparent microviscosity of the vesicles. Moreover, lipid peroxidation increased anisotropy more effectively than variations in the ratios of PE vs. PC. Thus, peroxidation of 5-10% of the phospholipids produced the same anisotropy increase as a 20% increase in the ratio of PE vs. PC. Analysis of vesicle turbidity suggested that fusion was also more readily achieved through lipid peroxidation. When liposomes were incubated with 0.4 U/ml of snake venom phospholipase A2, a direct correlation was found between the degree of lipid peroxidation and the extent of phospholipid hydrolysis. The more unsaturated phospholipid, PE, was most extensively hydrolyzed following peroxidation. Increasing the proportion of PE also resulted in more extensive phospholipid hydrolysis. These findings indicate that lipid peroxidation produces a general increase in membrane viscosity which is associated with vesicle instability and enhanced phospholipase A2 attack. A structural basis for membrane phospholipase A2 activation as a consequence of lipid peroxidation is discussed in light of these findings.

Differential involvement of gp130 signalling pathways in modulating tobacco carcinogen-induced lung tumourigenesis.

Interleukin (IL)-6 family cytokines signal exclusively via the gp130 coreceptor, and are implicated in smoking-associated lung cancer, the most lethal cancer worldwide. However, the role of gp130 signalling pathways in transducing the carcinogenic effects of tobacco-related compounds is ill-defined. Here, we report that lung tumourigenesis induced by the potent tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (Nicotine-derived Nitrosamine Ketone; NNK) is suppressed in gp130(F/F) knock-in mice characterized by the contrasting gp130-dependant hypoactivation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) and phosphatidylinositol 3-kinase/Akt, and hyperactivation of signal transducer and activator of transcription (STAT)3 signalling cascades. Specifically, in response to NNK, the absolute number and size of lung lesions in gp130(F/F) mice were significantly reduced compared with gp130(+/+) littermate controls, and associated with lower cellular proliferation without any alteration to the level of apoptosis in gp130(F/F) lung tumours. At the molecular level, reduced activation of ERK MAPK, but not Akt, was observed in lung tumours of gp130(F/F) mice, and corresponded with impaired expression of several tumour suppressor genes (for example, Trp53, Tsc2). Notably, STAT3 was not activated in the lungs of gp130(+/+) mice by NNK, and genetic normalization of STAT3 activation in gp130(F/F):Stat3(-/+) mice had no effect on NNK-induced tumourigenesis. The expression of tumour suppressor genes was reduced in tumours from current versus never-smoking lung cancer patients, and in vitro pharmacological inhibition of ERK MAPK signalling in human lung cancer cells abrogated NNK-induced downmodulation of tumour suppressor gene expression. Among IL-6 cytokine family members, IL-6 gene expression was specifically upregulated by NNK in vitro and in vivo, and inversely correlated with tumour suppressor gene expression. Collectively, our data reveal that a key molecular mechanism by which NNK promotes tumour cell proliferation during tobacco carcinogen-induced lung carcinogenesis is via upregulation of IL-6 and the preferential usage of gp130-dependant ERK MAPK signalling to downmodulate tumour suppressor gene expression.

Lipid peroxidation and modification of lipid composition in an endothelial cell model of ischemia and reperfusion.

Among the changes that accompany the development of ischemia are alterations in the composition and turnover of membrane phospholipids. To study these effects, a cell culture model was developed to facilitate accurate measurements of lipids over varying intervals of ischemia and reperfusion (I/R). In order to mimic ischemia, rabbit aortic endothelial cells were grown to confluency on collagen coated beads and the bead cultures allowed to settle to the bottom of a conical test tube or spectrofluorometric cuvette. The cell-coated beads were then resuspended in media to simulate the process of reperfusion. Survival after ischemia/reperfusion, was determined by measurements of cellular replating efficiency, and found to decrease after periods longer than three hours of ischemia (followed by 24 h of reperfusion). Plating efficiencies were reduced to nearly 50% after 5 h of ischemia followed by reperfusion. Release of LDH inversely correlated with cell survival, and lactate production, ATP levels, and extracellular H2O2 concentration were all affected by the duration of ischemia. These changes could be directly related to rates of cellular oxygen consumption which decreased by 50% after 5 h of ischemia, while the percentage of oxygen consumption not be inhibitable by cyanide, increased. Release of esterified fatty acids, which was partly inhibited by the phospholipase A2 inhibitor, mepacrine, was stimulated by increasing periods of ischemia while the incorporation of free fatty acids into phospholipids was inhibited. The incorporation of arachidonic acid was inhibited to a lesser degree than that of oleic or linoleic acids with a resulting change in phospholipid fatty acyl composition favoring greater proportions of unsaturated fatty acids. In some experiments, the effects of vitamin E or ascorbic acid administered prior to ischemia were studied. The degree of fatty acid unsaturation, fatty acid incorporation into phospholipids, and release from phospholipids into the free fatty acid pool during ischemia/reperfusion were not affected by prior administration of vitamin E or ascorbic acid. However, the extent of lipid peroxidation during ischemia was inhibited by 100 mM ascorbic acid when present during the ischemia/reperfusion period, but not by vitamin E administered for 24 h prior to ischemia. Ascorbic acid treatment, but not vitamin E, also enabled cells to recover substantial amounts of the ATP lost following prolonged ischemia. The ATP recovery corresponded to an increased cell survival and decreased lipid peroxidation. Progressive intervals of ischemia followed by reperfusion result in compromised cell respiratory activity and decreased ATP production, and decreased phospholipid acylation leading to net hydrolysis. The associated changes in phospholipid composition, and specifically increased unsaturation appear to favor peroxidation of membrane phospholipids.

beta-Adrenergic agonists increase phosphorylation of elongation factor 2 in cardiomyocytes without eliciting calcium-independent eEF2 kinase activity.

The beta-adrenergic agonist isoproterenol increased the phosphorylation of elongation factor eEF2 in ventricular cardiomyocytes from adult rats (ARVC). Phosphorylation of eEF2 inhibits its activity, and protein synthesis was inhibited in ARVC concomitantly with increased eEF2 phosphorylation. eEF2 kinase activity in ARVC extracts was completely dependent upon Ca(2+)/calmodulin. In contrast to other cell types, however, treatments designed to raise intracellular cAMP failed to induce Ca(2+)/calmodulin-independent activity. Instead, they increased maximal eEF2 kinase activity. Similar data were obtained when partially purified ARVC eEF2 kinase was treated with cAMP-dependent protein kinase in vitro. These data suggest that ARVC possess a distinct isoform of eEF2 kinase.

Lipid hydroperoxide-induced peroxidation and turnover of endothelial cell phospholipids.

The effects of lipid peroxidation on rabbit aortic endothelial cell phospholipid turnover was studied using linoleic acid hydroperoxide (LOOH). Following treatments with 20-40 microM LOOH, cells prelabeled with either arachidonic acid (20:4) or oleic acid (18:1) showed a movement of these fatty acids out of the phospholipids and into neutral lipid and free fatty acid pools. There was also a release of radioactive free fatty acids and phospholipids into the media, which was significantly increased as compared to cells maintained under standard culture conditions. Fatty acid uptake and distribution among phospholipid pools was also affected by LOOH treatment where incorporation of 20:4 and 18:1 into phosphatidylcholine (PC) decreased, while uptake into phosphatidylinositol (PI) increased after 1 h of incubation with 40 microM LOOH. These effects were also inhibited by vitamin E. In cells prelabeled with 20:4 or 18:1 under conditions where approximately 99% of the fatty acids were incorporated into neutral and phospholipid pools, LOOH treatment produced a decrease in radioactivity associated with PC, while the specific activity of PI increased. The extent of these changes was greater for 20:4 than 18:1, but in each case the effects were inhibited by vitamin E. The temporal pattern of uptake for labeled choline and inositol after LOOH treatments paralleled those found for fatty acid incorporation. These cell responses indicate that induction of lipid peroxidation produces rapid fatty acid release and phospholipid turnover involving repair as well as de novo synthesis. The implications of these effects on turnover of specific phospholipids and cell responses to oxidative stress are discussed.

Linoleic acid hydroperoxide-induced peroxidation of endothelial cell phospholipids and cytotoxicity.

Peroxidation of endothelial cell phospholipids was examined following treatments with linoleic acid hydroperoxide. The treatment effects were analyzed over a range of toxicities and exposure intervals as determined by cell plating efficiencies and survival. Over the concentration ranges where lipid peroxidation was evident (20-40 microM treatments in complete medium), significant cytotoxicity was apparent after 1 h of exposure. The extent of toxicity was dependent on the time interval between the end of peroxide treatment and replating of cells. Maximum toxicity was found when cells were replated 1-3 h after treatment. When cells were replated 4 h after treatment a linear increase in cell survival was found as a function of replating time following peroxide exposure. Analysis of cell phospholipids by HPLC after 1 h of exposure to linoleic acid hydroperoxide revealed that peroxidation (evidenced by conjugated diene content) had taken place among a number of phospholipid species with the most marked increases in phosphatidylcholine. Analysis of the fatty acyl composition of phospholipids also showed that the proportions of polyunsaturated fatty acids were reduced relative to saturated fatty acids, indicating peroxidative damage to phospholipids. Pretreatment of cells with vitamin E prevented the peroxidation of all phospholipids and blocked the cytotoxic action of linoleic acid hydroperoxide. These findings indicate that an immediate cytotoxic action of lipid hydroperoxide is associated with peroxidation of membrane phospholipids. This cytotoxicity is a transient effect, and cells surviving the acute injury display a time-dependent increase in plating efficiency representing a period of repair.

Some studies on cytisine and its methylated derivatives.

1. In mice cytisine hydrochloride is less toxic intravenously than nicotine hydrogen tartrate, but more toxic by intraperitoneal or oral administration. Compared with cytisine, caulophylline hydrogen iodide is one-fifth to one-tenth as toxic and caulophylline methiodide is less than one-thirtieth as toxic.2. The surprising low oral toxicity of cytisine and nicotine may be ascribed to the method of administration; if the drug is placed directly in the stomach there is no possibility of absorption through buccal mucous membranes.3. The peripheral effects of nicotine, cytisine and caulophylline are similar, though on some preparations those of nicotine last longer. In most tests cytisine is active in doses from a quarter to three-quarters of those of nicotine, caulophylline in doses from 10 to 20 times those of cytisine. Caulophylline methiodide is virtually inactive.4. Cytisine and caulophylline may differ from nicotine in their central effects.5. Cytisine and caulophylline are active as the cations. The pKa of cytisine is 7.92 and that of caulophylline is 7.04; the difference accounts, in part, for the weaker activity of caulophylline. The caulophylline ion is generally one-sixth to one-third as active as the cytisine ion.6. The introduction of the second methyl group to form the quaternary salt does not appear to cause a dramatic change in the conformation of the molecule. Caulophylline methiodide appears to be feebly active because it has feeble affinity.

Antibodies to polymerized albumin in woodchuck hepatitis virus infection.

Polymerized human serum albumin may play a role in the entry of hepatitis B virus into hepatocytes, and antibodies to polyalbumin that frequently appear during acute hepatitis may aid the process of viral clearance. We developed an enzyme-linked immunosorbent assay for antibodies to polymerized woodchuck albumin to enable us to evaluate further the role of these antibodies in an animal model system. Sera from 17 uninfected adult woodchucks and 8 newborns showed no binding to control plates coated with woodchuck transferrin, woodchuck albumin, or polymerized human serum albumin. One of 8 newborn animals demonstrated a significant antibody titer to polymerized woodchuck albumin, and 16 of 17 adults without evidence of prior woodchuck hepatitis virus infection had measurable serum antibody titers. Antibodies to polymerized woodchuck albumin could be adsorbed by prior incubation with the antigen. In 2 animals subjected to experimental infection, significant rises in polyalbumin antibody were seen. When 4 adult woodchucks were immunized with woodchuck polyalbumin, significant increases in antibody titer were observed in 2 of the 4 animals. Of the 4 immunized and 4 controls subsequently challenged with woodchuck hepatitis virus, 7 became viremic and all 8 developed antibody to woodchuck hepatitis virus core antigen. We conclude that naturally occurring antibodies to polymerized woodchuck albumin are observed in most adult woodchucks in the absence of woodchuck hepatitis virus infection and do not seem to confer immunity against infection with this virus.

Panic disorder or social phobia: which is worse?

Twenty-eight patients with panic disorder (PD) and 30 with social phobia (SP) were compared on demographic and psychopathology measures. The demographic comparisons showed that, although people with SP were better educated, they were more likely to be single, living alone, and unemployed. The comparisons of psychopathology showed that the proportion of people with PD and SP with a life time major affective disorder did not differ, nor did the two groups differ on the proportion of Ss reporting past suicide attempts. However, a greater proportion of patients with SP had Brief Michigan Alcohol Screening Test scores above 5, indicating alcohol abuse problems. The implications of these findings are discussed.

Teaching second-year medical students about wife battering.

PIP: This paper discusses the necessity to revise the health professional curricula. The reason for this is to change the longstanding practices and attitudes that have failed to promote women's health. However, the change is insufficient as long as there is a body of untrained and biased leadership in practice, which is evident among some health personnel who routinely underestimate the extent of wife abuse in their clients. Moreover, in a study of hospital emergency departments, 28% believed that less than 1% of emergency room patients were victims of violence and only 13% estimated 10% or more. In addition, a survey of family therapists found that 60% did not believe that family violence was a significant problem among their clients. Another study found that 40% did not recognize clear evidence of violence in the vignettes provided. In view of these findings, it is concluded that even if we succeed in educating medical students, their role models and supervisors may be less informed and may undo the work done by teachers with scorn and ridicule. Hence, a comprehensive approach to continuing and postgraduate medical education is needed to support the efforts of medical school teaching.^ieng

Cholesterol autoxidation in phospholipid membrane bilayers.

Lipid peroxidation in unilamellar liposomes of known cholesterol-phospholipid composition was monitored under conditions of autoxidation or as induced by a superoxide radical generating system, gamma-irradiation or cumene hydroperoxide. Formation of cholesterol oxidation products was indexed to the level of lipid peroxidation. The major cholesterol oxidation products identified were 7-keto-cholesterol, isomeric cholesterol 5,6-epoxides, isomeric 7-hydroperoxides and isomeric 3,7-cholestane diols. Other commonly encountered products included 3,5-cholestadiene-7-one and cholestane-3 beta, 5 alpha, 6 beta-triol. Superoxide-dependent peroxidation required iron and produced a gradual increase in 7-keto-cholesterol and cholesterol epoxides. Cholesterol oxidation was greatest in liposomes containing high proportions of unsaturated phospholipid to cholesterol (4:1 molar ratio), intermediate with low phospholipid to cholesterol ratios (2:1) and least in liposomes prepared with dipalmitoylphosphatidylcholine and cholesterol. This relationship held regardless of the oxidizing conditions used. Cumene hydroperoxide-dependent lipid peroxidation and/or more prolonged oxidations with other oxidizing systems yielded a variety of products where cholesterol-5 beta,6 beta-epoxide, 7-ketocholesterol and the 7-hydroperoxides were most consistently elevated. Oxyradical initiation of lipid peroxidation produced a pattern of cholesterol oxidation products distinguishable from the pattern derived by cumene hydroperoxide-dependent peroxidation. Our findings indicate that cholesterol autoxidation in biological membranes is modeled by the peroxide-induced oxidation of liposomes bearing unsaturated fatty acids and suggest that a number of cholesterol oxidation products are derived from peroxide-dependent propagation reactions occurring in biomembranes.

Women's views regarding participation in a proposed randomized controlled trial of twin delivery.

OBJECTIVE: To determine the views of women regarding participation in a proposed multicentre randomized controlled trial comparing planned vaginal birth to planned Caesarean delivery for twins at 32 or more weeks' gestation, in which the first twin (twin A) is presenting as a vertex. METHODS: Pregnant women with a known twin gestation were recruited from 2 hospital centres. Written information was provided about the proposed Twin Birth Study, and the women were then requested to complete a questionnaire to determine their views regarding participation in the proposed trial. RESULTS: Of the 64 women recruited for the study, 31 (48%) indicated they would be willing to consider participating in the proposed trial (95% CI, 37-60%), 14 (22%) were unsure about trial participation (95% CI, 13-33%), and 19 (30%) indicated they would not be willing to participate in the proposed study (95% CI, 20-42%). The most common reason for agreement to participation was altruism (n = 28). Those who responded "not sure" wished to speak with their partner (n = 5) or their doctor (n = 8) before deciding on participation. Of those who indicated they would not participate in the proposed trial, 12 (63%) indicated they preferred to have a vaginal birth, and 7 (37%) preferred to have a Caesarean section. CONCLUSIONS: Almost half the women in our sample were agreeable to considering their participation in a randomized trial that will compare planned vaginal birth to planned Caesarean section for twins at 32 or more weeks' gestation with twin A presenting as a vertex. Altruism was the most common reason for agreeing to participate, whereas preference for a specific mode of delivery was the most common reason for declining participation.