Socioeconomic and ethnic inequities within organised colorectal cancer screening programmes worldwide.

OBJECTIVE: Colorectal cancer (CRC) screening programmes can reduce CRC mortality. However, the implementation of a screening programme may create or exacerbate socioeconomic and ethnic health inequities if participation varies by subgroup. We determined which organised programmes characterise participation inequities by socioeconomic and ethnic subgroups, and assessed the variation in subgroup participation among programmes collecting group-specific data. DESIGN: Employing a literature review and survey among leaders of national or regional screening programmes, this study identified published and unpublished data on participation by socioeconomic status and ethnicity. We assessed programmes offering faecal occult blood tests (FOBT) for screening. Primary outcome was screening participation rate. RESULTS: Across 24 organised FOBT-screening programmes meeting the inclusion criteria, participation rates ranged from 21% to 73%. Most programmes (13/24, 54%) did not collect data on participation by socioeconomic status and ethnicity. Among the 11 programmes with data on participation by socioeconomic status, 90% (28/31 publications) reported lower participation among lower socioeconomic groups. Differences across socioeconomic gradients were moderate (66% vs 71%) to severe (35% vs 61%). Only six programmes reported participation results by ethnicity. Ethnic differences were moderate, though only limited data were available for evaluation. CONCLUSIONS: Across organised CRC screening programmes worldwide, variation in participation by socioeconomic status and ethnicity is often not assessed. However, when measured, marked disparities in participation by socioeconomic status have been observed. Limited data were available to assess inequities by ethnicity. To avoid exacerbating health inequities, screening programmes should systematically monitor participation by socioeconomic status and ethnicity, and investigate and address determinants of low participation.

A three-component cognitive behavioural lifestyle program for preconceptional weight-loss in women with polycystic ovary syndrome (PCOS): a protocol for a randomized controlled trial.

BACKGROUND: Obesity in women with polycystic ovary syndrome (PCOS) negatively affects all clinical features, and a 5 to 10% weight loss has shown promising results on reproductive, metabolic and psychological level. Incorporating a healthy diet, increasing physical activity and changing dysfunctional thought patterns in women with PCOS are key points in losing weight. The biggest challenge in weight management programs is to achieve a reasonable and sustainable weight loss. The aim of this study is to explore whether Cognitive Behavioural Therapy (CBT) by a mental health professional, working in a multidisciplinary team with a dietician and a physical therapist (a three-component intervention), is more effective for weight loss in the long term, within 12 months. We will also explore whether mobile phone applications are effective in supporting behavioural change and sustainable weight loss. METHODS: The present study is a longitudinal randomized controlled trial (RCT) to study the effectiveness of a three-component 1-year cognitive-behavioural lifestyle intervention in overweight/obese women with PCOS. A total of 210 participants are randomly assigned to three groups: 1) CBT provided by the multidisciplinary team or; 2) CBT provided by the multidisciplinary team and Short Message Service (SMS) or; 3) usual care: encourage weight loss through publicly available services (control group). The primary aim of the 12-month intervention is to explore whether a three-component 1-year cognitive-behavioural lifestyle intervention is effective to decrease weight, when compared to usual care. Secondary outcomes include: the effect of the intervention on the PCOS phenotype, waist circumference, waist to hip ratio, ovulation rates, total testosterone, SHBG, free androgen index (FAI), AMH, hirsutism, acne, fasting glucose, blood pressure and all psychological parameters. Additionally, we assessed time to pregnancy, ongoing pregnancies, clinical pregnancies, miscarriages and birth weight. All outcome variables are measured at the start of the study, and again at 3 months, 6 months, nine months and 12 months. DISCUSSION: We expect that CBT provided by a multidisciplinary team, especially combined with SMS, is effective in developing a healthy lifestyle and achieving a long-term weight loss in women with PCOS. Losing 5- 10% body weight improves various PCOS characteristics. Consequently, we expect to show that CBT provided by a multidisciplinary team improves reproductive and metabolic outcomes, as well as quality of life, while at the same time being cost-effective. TRIAL REGISTRATION: Registered at the Netherlands National Trial Register with number NTR2450 on August 2nd, 2010.

Identification, Synthesis, and Field Tests of the Sex Pheromone of Margarodes prieskaensis (Jakubski).

Here, we report the identification and synthesis of the sex pheromone of female Margarodes prieskaensis (Jakubski), and the attractiveness of the synthetic pheromone to males in field trapping tests. Volatile organic compounds were collected from virgin females using a sample enrichment probe (SEP). Analyses by gas chromatography coupled to mass spectrometry revealed the presence of only two constituents. By scaling up the SEP, sufficient of the major constituent was collected for 1H and 13C nuclear magnetic resonance (NMR) analyses and ancillary NMR techniques. The sex attractant was identified as (2R,4R,6R,8R)-2,4,6,8-tetramethylundecan-1-ol. The enantiomerically pure compound was synthesized from octadecyl (2R,4R,6R,8R)-2,4,6,8-tetramethylundecanoate, a minor component of the uropygial (preen) gland secretion of the domestic goose, Anser domesticus. Field trapping experiments, carried out in vineyards in the Northern Cape Province of South Africa, showed that the synthetic compound was as attractive to winged males of M. prieskaensis as virgin females. The second compound detected was identified as the corresponding acetate, but addition of this did not affect the attractiveness of the major component. We believe this to be the first identification of a sex attractant of the Margarodidae.

Predictive action tracking without motor experience in 8-month-old infants.

A popular idea in cognitive neuroscience is that to predict others' actions, observers need to map those actions onto their own motor repertoire. If this is true, infants with a relatively limited motor repertoire should be unable to predict actions with which they have no previous motor experience. We investigated this idea by presenting pre-walking infants with videos of upright and inverted stepping actions that were briefly occluded from view, followed by either a correct (time-coherent) or an incorrect (time-incoherent) continuation of the action (Experiment 1). Pre-walking infants looked significantly longer to the still frame after the incorrect compared to the correct continuations of the upright, but not the inverted stepping actions. This demonstrates that motor experience is not necessary for predictive tracking of action kinematics. In a follow-up study (Experiment 2), we investigated sensorimotor cortex activation as a neural indication of predictive action tracking in another group of pre-walking infants. Infants showed significantly more sensorimotor cortex activation during the occlusion of the upright stepping actions that the infants in Experiment 1 could predictively track, than during the occlusion of the inverted stepping actions that the infants in Experiment 1 could not predictively track. Taken together, these findings are inconsistent with the idea that motor experience is necessary for the predictive tracking of action kinematics, and suggest that infants may be able to use their extensive experience with observing others' actions to generate real-time action predictions.

OC-10 - Disseminated intravascular coagulation at diagnosis strongly predicts both arterial and venous thrombosis in acute myeloid leukemia patients.

INTRODUCTION: Acute myeloid leukemia (AML) is associated with a slightly increased risk of VTE with an incidence of 1.7-8.9%, but only limited data are available. The mechanism of the occurrence of thrombosis in hematological disorders is still unresolved. Disseminated intravascular coagulation (DIC) is associated with VTE and bleeding in acute promyelocytic leukemia and acute lymphoblastic leukemia. Although DIC has also been reported in AML, no data exist on the relationship between DIC and VTE in AML patients. AIM: We hypothesized that the presence of DIC at diagnosis of AML may contribute to the risk of both venous and arterial thrombosis in AML. Therefore we studied a large cohort of adult patients with newly diagnosed AML aged <65 years by measuring DIC parameters at diagnosis prior to treatment and assessing the occurrence of both venous and arterial thrombosis during follow up. The findings of this study were validated in a second large cohort of patient with newly diagnosed AML aged >60 years. MATERIALS AND METHODS: In a prospective study we analysed markers of DIC and their association with the occurrence of thrombosis during follow up in a cohort of 272 young AML patients (aged 18-65) and a validation cohort of 132 elderly AML patients (aged >60) patients that were all treated with intensive chemotherapy. DIC parameters (fibrinogen, D-dimer, alpha-2-antiplasmin, antitrombin, prothrombin time and platelets) were measured at presentation with AML before start of induction chemotherapy. The DIC score according to the International Society of Thrombosis and Haemostasis DIC scoring systemwas calculated of all patients. RESULTS: The prevalence of thrombosis was 8.7% (4.7% venous, 4.0% arterial) in young patients over a median follow up of 478 days and 10.4% (4.4% venous, 5.9% arterial) in elderly patients. Most thrombotic events (66%) occurred before start of the second course of chemotherapy. The calculated DIC score significantly predicted venous and arterial thrombosis with a Hazard Ratio (HR) for a high DIC score (=>5) of 4.79 (1.71-13.45) in the cohort of young AML patients. These results were confirmed in our validation cohort of elderly AML patients. (HR 11.08 (3.23-38.06)). Of all DIC parameters D-dimer levels are most predictive for thrombosis with a HR of 12.3 (3.39-42.64) in the cohort of young AML patients and a HR of 7.82 (1.95-31.38) in the elderly cohort for a D-dimer >4.0 mg/L. CONCLUSIONS: It is concluded that both venous and arterial thrombosis occurs in around 10% of AML patients treated with intensive chemotherapy, which can be predicted by the presence of DIC, or individual DIC parameters at time of AML diagnosis.

ESHRE guideline: routine psychosocial care in infertility and medically assisted reproduction-a guide for fertility staff.

STUDY QUESTION: Based on the best available evidence in the literature, what is the optimal management of routine psychosocial care at infertility and medically assisted reproduction (MAR) clinics? SUMMARY ANSWER: Using the structured methodology of the Manual for the European Society of Human Reproduction and Embryology (ESHRE) Guideline Development, 120 recommendations were formulated that answered the 12 key questions on optimal management of routine psychosocial care by all fertility staff. WHAT IS ALREADY KNOWN: The 2002 ESHRE Guidelines for counselling in infertility has been a reference point for best psychosocial care in infertility for years, but this guideline needed updating and did not focus on routine psychosocial care that can be delivered by all fertility staff. STUDY, DESIGN, SIZE, DURATION: This guideline was produced by a group of experts in the field according to the 12-step process described in the ESHRE Manual for Guideline Development. After scoping the guideline and listing a set of 12 key questions in PICO (Patient, Intervention, Comparison and Outcome) format, thorough systematic searches of the literature were conducted; evidence from papers published until April 2014 was collected, evaluated for quality and analysed. A summary of evidence was written in a reply to each of the key questions and used as the basis for recommendations, which were defined by consensus within the guideline development group (GDG). Patient and additional clinical input was collected during the scoping and the review phase of the guideline development. PARTICIPANTS/MATERIALS, SETTING, METHODS: The guideline group, comprising psychologists, two medical doctors, a midwife, a patient representative and a methodological expert, met three times to discuss evidence and reach consensus on the recommendations. MAIN RESULTS AND THE ROLE OF CHANCE THE GUIDELINE PROVIDES: 120 recommendations that aim at guiding fertility clinic staff in providing optimal evidence-based routine psychosocial care to patients dealing with infertility and MAR. The guideline is written in two sections. The first section describes patients' preferences regarding the psychosocial care they would like to receive at clinics and how this care is associated with their well-being. The second section of the guideline provides information about the psychosocial needs patients experience across their treatment pathway (before, during and after treatment) and how fertility clinic staff can detect and address these. Needs refer to conditions assumed necessary for patients to have a healthy experience of the fertility treatment. Needs can be behavioural (lifestyle, exercise, nutrition and compliance), relational (relationship with partner if there is one, family friends and larger network, and work), emotional (well-being, e.g. anxiety, depression and quality of life) and cognitive (treatment concerns and knowledge). LIMITATIONS, REASONS FOR CAUTION: We identified many areas in care for which robust evidence was lacking. Gaps in evidence were addressed by formulating good practice points, based on the expert opinion of the GDG, but it is critical for such recommendations to be empirically validated. WIDER IMPLICATIONS OF THE FINDINGS: The evidence presented in this guideline shows that providing routine psychosocial care is associated with or has potential to reduce stress and concerns about medical procedures and improve lifestyle outcomes, fertility-related knowledge, patient well-being and compliance with treatment. As only 45 (36.0%) of the 125 recommendations were based on high-quality evidence, the guideline group formulated recommendations to guide future research with the aim of increasing the body of evidence.

Bullying, abuse and family conflict as risk factors for chronic pain among Dutch adolescents.

PURPOSE: Psychosocial stress seems to serve as an important risk factor for the occurrence of pain. The present study aims to examine if early adversities, e.g. bullying, abuse and family conflict are risk factors for chronic pain in adolescents. The secondary aim of the present study was to describe the pain characteristics of chronic pain in adolescents in a community sample of Dutch adolescents. METHODS: Participants in the present study were 15,220 adolescents, attending schools (grade 7 and 8) in Rotterdam, the Netherlands. Chronic pain was measured with a newly developed questionnaire; the Pain Barometer. Early adversities were measured using single-item questions from the Rotterdam Youth Monitor, a longitudinal youth health surveillance system. Cross-sectional associations between early adversities and chronic pain were investigated using logistic multilevel analysis, adjusted for potential confounding. RESULTS: In school year 2010-2011, 9.2% of the 15,220 adolescents reported chronic pain. Physical abuse by others (OR = 1.51, 95% CI =  1.07-2.14), sexual abuse (OR = 1.46, 95% CI = 1.05-2.05), family conflict (OR = 1.79, 95% C = 1.61-1.99) and being bullied (OR = 1.23, 95% CI = 1.17-1.29) are more common in adolescents with chronic pain. Physical abuse (OR = 1.28, 95% CI = 0.95-1.71) by parents and parental divorce (OR = 1.07, 95% CI = 0.93-1.22) were not significantly related to chronic pain. CONCLUSIONS: The results of the present study suggest that bullying, abuse and family conflict may be risk factors for chronic pain in adolescents. Early signalling these stressors might prevent chronic pain. IMPLICATIONS AND CONTRIBUTION: Early adversities, i.e. physical and sexual abuse, being bullied and family conflict, might be risk factors for developing chronic pain. In addition, the present study suggests that chronic pain is common among Dutch adolescents and interferes with their daily activities. If future studies confirm our results, this knowledge can be used to improve the signalling and prevention of chronic pain in adolescents.

Elucidating the behavior of physical fatigue and mental fatigue in cancer patients: a review of the literature.

BACKGROUND: Although the multidimensional nature of cancer-related fatigue is widely accepted, it could be questioned whether fatigue dimensions are expressions of one symptom (multidimensional concept) or expressions of several phenomena that are all called fatigue but actually are separate symptoms (multiple-symptom concept). METHODS: Therefore, we investigated in this review whether physical fatigue and mental fatigue behave differently in cancer patients by studying their intensity in different stages of cancer, their changes in intensity during anti-tumor therapy, the variables to which they are related, and their changes in intensity by interventions on fatigue. RESULTS: In some studies, physical fatigue and mental fatigue behaved similarly: they were both more intense in cancer patients than in healthy controls, and sometimes, they had the same course during anti-tumor therapy, or both improved during an intervention. On the contrary, there were some studies suggesting that physical fatigue and mental fatigue behaved differently: physical fatigue seemed to be more prominent than mental fatigue in some stages of the disease trajectory; several studies reported changes in physical fatigue not accompanied by changes in mental fatigue during anti-tumor therapy or by interventions aimed to relieve fatigue; and physical fatigue and mental fatigue had different correlates. CONCLUSIONS: In conclusion, we found some studies in which physical fatigue and mental fatigue behaved differently. These findings might indicate that physical fatigue and mental fatigue are separate phenomena. To prove this multiple-symptom concept, studies on the pathophysiological mechanisms leading either to physical fatigue or to mental fatigue are urgently needed.

The effect of a short message service maintenance treatment on body mass index and psychological well-being in overweight and obese children: a randomized controlled trial.

OBJECTIVE: Maintaining weight loss results in childhood obesity treatment is difficult to achieve. Self-management techniques such as self-monitoring are associated with increased weight loss and maintenance. This study analyzes whether self-monitoring of lifestyle behaviours through a short message service maintenance treatment (SMSMT) via mobile phones with personalized feedback positively effects weight, lifestyle behaviours and psychological well-being in obese children. METHODS: After 3 months of behavioural lifestyle treatment, 141 overweight and obese children (7-12 years) were randomly assigned to an intervention group receiving SMSMT for 9 months (n = 73) or to the control group (n = 68). The intervention group sent weekly self-monitoring data on exercise and eating behaviour and their mood via mobile phones. In return, they received tailored feedback messages. Primary treatment outcomes were weight, eating behaviour and psychological well-being, i.e. competence, self-esteem and quality of life. Secondary outcome was adherence to the SMSMT. Data were analyzed with mixed modelling. RESULTS: SMSMT did not improve treatment outcomes. Controls gained temporarily in physical health scores (P = 0.01). SMSMT completers sent on average every 2 weeks an SMS. Children who had greater weight loss during the first 3 months of lifestyle treatment sent more SMSs (P = 0.04). CONCLUSIONS: We did not find a positive effect of SMSMT on weight, eating behaviour or psychological well-being in obese children. SMSMT seems to be a feasible method of treatment delivery. Future research should study variations of SMSMT to investigate how SMSMT can be more effective.

Psychological well-being and sexarche in women with polycystic ovary syndrome.

BACKGROUND: The characteristics of polycystic ovary syndrome (PCOS) such as hyperandrogenism and anovulation can be highly stressful and might negatively affect psychological well-being and sexuality. The objective of this study was to evaluate the association between PCOS characteristics and psychological well-being as well as sexarche. METHODS: Patients (n = 1148) underwent standardized clinical evaluation. Psychological well-being was investigated in 480 patients with the Rosenberg self-esteem scale (RSES), the body cathexis scale (BCS) and the fear of negative appearance evaluation scale (FNAES). Sexarche was also assessed. RESULTS: Amenorrhoea was associated with lower self-esteem (P = 0.03), greater fear of negative appearance evaluation (P = 0.01) and earlier sexarche (P= 0.004). Hyperandrogenism and acne were associated with poorer body satisfaction (P = 0.03, 0.02, respectively). Hirsutism and BMI were negatively associated with all psychological variables (RSES, P = 0.01; BCS, P = 0.05; FNAES, P = 0.02 and RSES, P = 0.03; BCS, P = 0.001; FNAES, P = 0.03, respectively). CONCLUSIONS: Our results suggest that menstrual irregularities might be related to sexarche. Moreover, this study stresses that the treatment of women with PCOS should notably focus on physical but also on psychological and sexual characteristics.

Why do couples drop-out from IVF treatment? A prospective cohort study.

BACKGROUND: Cumulative IVF pregnancy rates are compromised by the large number of couples who drop-out of treatment before achieving pregnancy. The aim of this study was to identify the role of the treatment strategy applied, and potential other factors that influence the decision of couples to discontinue treatment. METHODS: The incidence of drop-out from IVF treatment and factors related to drop-out were studied in a cohort of IVF patients aged <38 years embarking on IVF treatment either with a mild or a standard treatment strategy for a planned maximum number of treatment cycles. RESULTS: Of the 384 couples studied, 17% dropped out of IVF treatment. The physical or psychological burden of treatment was the most frequent cause of drop-out (28%). The application of a mild treatment strategy (mild ovarian stimulation along with the transfer of a single embryo) significantly reduced the chance of drop-out (hazard ratio (HR) 0.55; 95% confidence interval (CI), 0.31-0.96). When a mild IVF strategy was employed, the association between the baseline anxiety score and drop-out was reduced by >50%. The presence of severe male subfertility (HR 4.80; 95% CI, 1.63-14.13) and the failure to achieve embryo transfer (odds ratio 0.41; 95% CI, 0.24-0.72) were also related to drop-out. CONCLUSIONS: Reducing drop-out rate is crucial to further improve the efficacy and cost-effectiveness of IVF treatment. An important factor determining the risk of drop-out is the burden of the treatment strategy. The application of a mild treatment strategy and managing patient's expectations might reduce drop-out rates.

[Reduction of patient discomfort, risks and costs, but not pregnancies, by a mild strategy for in-vitro fertilisation]. / Minder risico's, patiëntenongemak en kosten, maar niet minder zwangerschappen in de milde behandelstrategie voor ivf.

OBJECTIVE: To compare a so-called mild in-vitro fertilisation (IVF) treatment strategy with the standard IVF treatment on the following aspects: the chance of a pregnancy resulting in full-term live birth within 1 year, patient discomfort, multiple pregnancies, and costs. DESIGN: Randomised, open-label, prospective trial (www.controlledtrials.com, number ISRCTN35766970). METHOD: 404 patients were assigned to undergo either a mild treatment, consisting of ovarian stimulation with a gonadotrophin releasing hormone (GnRH) antagonist combined with single embryo transfer, or the standard treatment consisting of prolonged stimulation with a GnRH agonist combined with the transfer of two embryos. The primary outcome measures were: (1) the percentage of cumulative pregnancies within one year after randomisation leading to full-term live birth; (2) total costs per couple and child up to 6 weeks after expected delivery; and (3) overall patient discomfort. Analysis was done according to the intention-to-treat principle and was intended to show that the mild treatment was not inferior to the standard treatment; the non-inferiority threshold was -12.5%. RESULTS: The proportion of cumulative pregnancies resulting in full-term live birth after 1 year was 43.4% in the mild and 44.7% in the standard treatment group. The lower limit of the one-sided 95% confidence interval was equal to -9.8%. The respective proportion of couples with multiple pregnancies was 0.5% versus 13.1% (p < 0.0001), and the average total costs were Euro 8,333.- versus Euro 10,745.- (difference: Euro 2,412.-, 95% CI: 703-4,131). There were no statistically significant differences between the groups with regard to anxiety, depression, physical discomfort, and sleep quality. CONCLUSION: After 1 year of treatment, the cumulative percentage of pregnancies leading to full-term live birth and the total patient discomfort were the same for the mild treatment (average 2.3 IVF-cycles) and the standard treatment (average 1.7 IVF-cycles). The mild treatment significantly reduced the number of multiple pregnancies and the overall costs.

Low negative affect prior to treatment is associated with a decreased chance of live birth from a first IVF cycle.

BACKGROUND: Psychological variables, such as anxiety and depression, may have a negative impact on IVF outcomes, but the evidence remains inconclusive. Previous studies have usually measured a single psychological parameter with clinical pregnancy as the outcome. The objective of the current study was to determine whether pretreatment or procedural psychological variables in women undergoing a first IVF cycle affect the chance of achieving a live birth from that cycle. METHODS: Between February 2002 and February 2004, 391 women with an indication for IVF were recruited at two University Medical Centres in The Netherlands. Pretreatment anxiety and depression were measured with the Hospital Anxiety and Depression Scale. The Daily Record Keeping Chart was used to measure negative and positive affect before treatment and daily during ovarian stimulation. Multiple stepwise forward logistic regression analysis was performed with term live birth as the dependent variable. RESULTS: Regression analysis showed that women who expressed less negative affect at baseline were less likely to achieve live birth (P = 0.03). After one IVF cycle, women who received a standard IVF strategy were more likely to reach live birth delivery than those who received a mild IVF strategy (P = 0.002). A male/female indication for IVF was associated with a higher chance of achieving term live birth than a female only indication (P = 0.03). Age, duration of infertility or type of infertility were not independent predictors of live birth. CONCLUSIONS: The relationship between psychological parameters and IVF success rates is more complex than commonly believed. The expression of negative emotions before starting IVF might not be always detrimental for outcomes.

Prevention of catheter-related venous thrombosis with nadroparin in patients receiving chemotherapy for hematologic malignancies: a randomized, placebo-controlled study.

BACKGROUND: Hemato-oncology patients treated with intensive chemotherapy usually require the placement of a central venous catheter (CVC). CVCs are frequently complicated by catheter-related central venous thrombosis (CVT), which has been associated with an increased risk of pulmonary embolism and catheter-related infection. OBJECTIVES: To determine the efficacy and safety of thromboprophylaxis with s.c. low-molecular-weight heparin (nadroparin) administered once daily in a randomized placebo-controlled, double-blind trial in patients with hematologic malignancies. PATIENTS AND METHODS: Consecutive patients with hematologic malignancies requiring intensive chemotherapy including autologous stem cell transplantation were eligible. The patients were randomized to receive nadroparin 2850 antifactor Xa units once daily or placebo s.c. for 3 weeks. Venography was performed on day 21 after CVC insertion. Secondary outcomes were bleeding and catheter-related infection. RESULTS: In total, 113 patients were randomized to nadroparin or placebo, and 87 patients (77%) underwent venography. In total, 11 venographically proven catheter-related CVTs were diagnosed. The frequency of catheter-related CVT was not significantly different between study groups, namely four catheter-related CVTs in the placebo group [9%; 95% CI: 0.002-0.16] vs. seven catheter-related CVTs in the nadroparin group (17%; 95% CI: 0.06-0.28). In addition, no difference in the incidence of catheter-related infection or bleeding was observed between the groups. CONCLUSION: This study showed that the actual risk for catheter-related CVT in patients with hematologic malignancies is lower than suggested in earlier studies in cancer patients. Although prophylactic administration of nadroparin appeared to be safe in this group of patients with a high risk of bleeding, it cannot be recommended for the prevention of catheter-related CVT or catheter-related infection in patients with hematologic malignancies.

Colon cancer metastasis in mouse liver is not affected by hypercoagulability due to Factor V Leiden mutation.

Clinical trials have shown life-prolonging effects of antithrombotics in cancer patients, but the molecular mechanisms remain unknown due to the multitude of their effects. We investigated in a mouse model whether one of the targets of antithrombotic therapy, fibrin deposition, stimulates tumour development. Fibrin may provide either protection of cancer cells in the circulation against mechanical stress and the immune system, or form a matrix for tumours and/or angiogenesis in tumours to develop. Mice homozygous for Factor V Leiden (FVL), a mutation in one of the coagulation factors that facilitates fibrin formation, were used to investigate whether hypercoagulability affects tumour development in an experimental metastasis model. Liver metastases of colon cancer were induced in mice with the FVL mutation and wild-type littermates. At day 21, number and size of tumours at the liver surface, fibrin/fibrinogen distribution, vessel density and the presence of newly formed vessels in tumours were analysed. Number and size of tumours did not differ between mice with and without the FVL mutation. Fibrin/fibrinogen was found in the cytoplasm of hepatocytes and cancer cells, in blood vessels in liver and tumour tissue and diffusely distributed outside vessels in tumours, indicating leaky vessels. Vessel density and angiogenesis varied widely between tumours, but a pre-dominance for vessel-rich or vessel-poor tumours or vessel formation could not be found in either genotype. In conclusion, the FVL mutation has no effect on the development of secondary tumours of colon cancer in livers of mice. Fibrin deposition and thus inhibition of fibrin formation by anticoagulants do not seem to affect tumour development in this model.

The psychological impact of IVF failure after two or more cycles of IVF with a mild versus standard treatment strategy.

BACKGROUND: Failure of IVF treatment after a number of cycles can be devastating for couples. Although mild IVF strategies reduce the psychological burden of treatment, failure may cause feelings of regret that a more aggressive approach, including the transfer of two embryos, was not employed. In this study, the impact of treatment failure after two or more cycles on stress was studied, following treatment with a mild versus a standard treatment strategy. METHODS: Randomized controlled two-centre trial (ISRCTN35766970). Women were randomized to undergo mild ovarian stimulation (including GnRH antagonist co-treatment) and single embryo transfer (n = 197) or standard GnRH agonist long-protocol ovarian stimulation with double embryo transfer (n = 194). Participants completed the Hospital Anxiety and Depression Scale prior to commencing treatment and 1 week after the outcome of their final treatment cycle was known. Data from women who underwent two or more IVF cycles were subject to analysis (n = 253). RESULTS: Women who experienced treatment failure after standard IVF treatment presented more symptoms of depression 1 week after treatment termination compared with women who had undergone mild IVF: adjusted mean (+/-95% confidence interval) = 10.2 (+/-2.3) versus 5.4 (+/-1.8), respectively, P = 0.01. CONCLUSIONS: Failure of IVF treatment after a mild treatment strategy may result in fewer short-term symptoms of depression as compared to failure after a standard treatment strategy. These findings may further encourage the application of mild IVF treatment strategies in clinical practice.

Mechanisms of heparin induced anti-cancer activity in experimental cancer models.

BACKGROUND: Retrospective analyses of clinical trials and prospective clinical studies have suggested that heparins may have an effect on cancer survival. This putative anti-cancer activity of heparins is supported by data from studies in animal tumour models. OBJECTIVE: To clarify the various potential mechanisms of heparin anti-cancer activity we evaluated the data from pre-clinical studies in which heparins have been tested as anti-cancer therapy. METHODS: Pre-clinical studies, published between 1960 and 2005 were assessed. Data were collected on the type and dose of heparin used, duration of exposure to heparin, interval between heparin administration and cancer cell inoculation, and the animal tumour model used. In addition, a distinction was made in the analysis between heparin effects on the primary tumour or on established metastases and effects on the metastatic potential of infused cells. RESULTS: Heparins seemed to affect the formation of metastasis rather than the growth of primary tumours. Chemically modified heparins with no or limited anticoagulant activity also showed anti-metastatic properties. Possible mechanisms to explain the effects on the process of metastases include inhibition of blood coagulation, inhibition of cancer cell-platelet and -endothelial interactions by selectin inhibition and inhibition of cell invasion and angiogenesis. CONCLUSION: The anti-cancer activity of heparins depends more on inhibition of metastasis formation than on the effects on primary tumour growth. These effects are probably related to both coagulation and non-coagulation dependent factors. For a definitive proof of the anti-cancer activity of heparins in the clinic, prospective randomized trials especially in patients with early metastatic disease or in the adjuvant setting are urgently needed.

The psychological impact of mild ovarian stimulation combined with single embryo transfer compared with conventional IVF.

BACKGROUND: The objective of this study was to assess the psychological implications of mild ovarian stimulation combined with single embryo transfer (SET) during a first IVF cycle. METHODS: We conducted a randomized controlled two-centre trial. Three hundred and ninety-one couples were randomized to undergo either mild ovarian stimulation with GnRH antagonist co-treatment and SET (n=199) or conventional GnRH agonist long protocol ovarian stimulation with double embryo transfer (DET) (n=192). Women completed the Hospital Anxiety and Depression Scale, the Hopkins Symptom Checklist and the Subjective Sleep Quality Scale at baseline, on the first day of ovarian stimulation and following embryo transfer. Affect was assessed daily with the Daily Record Keeping Chart from the first day of ovarian stimulation until the day treatment outcome became known. RESULTS: The conventional IVF group experienced elevated levels of physical and depressive symptoms during pituitary downregulation. At oocyte retrieval, this group experienced more positive affect and less negative affect than the mild IVF group. In the conventional IVF group, cycle cancellation was associated with less positive and more negative affect. CONCLUSIONS: During the first IVF treatment cycle, mild ovarian stimulation and SET does not lead to more psychological complaints than conventional IVF.

Comparison of different treatment strategies in IVF with cumulative live birth over a given period of time as the primary end-point: methodological considerations on a randomized controlled non-inferiority trial.

BACKGROUND: We discuss methodological considerations related to a study in IVF, which compares the effectiveness, health economics and patient discomfort of two treatment strategies that differ in both ovarian stimulation and embryo transfer policies. METHODS: This was a randomized controlled clinical trial in two large Dutch IVF centres. The tested treatment strategies are: mild ovarian stimulation [including gonadotrophin-releasing hormone (GnRH) antagonist co-treatment] together with the transfer of one embryo, versus conventional stimulation (with GnRH agonist long protocol co-treatment) and the transfer of two embryos. Outcome measures are: (i) pregnancies resulting in term live birth; (ii) total costs per term live birth; and (iii) patient stress/discomfort per started IVF treatment, over a 12 month period. Power considerations for this study were an overall cumulative live birth rate of 45% for the conventional treatment strategy, with non-inferiority of the mild treatment strategy defined as a live birth rate no more than 12.5% lower compared with the conventional study arm. For a power of 80% and alpha of 0.05, 400 subjects are required. RESULTS: As planned, from February 2002 until February 2004, 410 patients were enrolled. CONCLUSIONS: This effectiveness study applies an integrated medical, health economics and psychological approach with term live birth over a given period of time after starting IVF as the end-point. Complete and timely patient enrolment vindicates many of the design decisions.