Is home-based monitoring of ovulation to time frozen embryo transfer a cost-effective alternative for hospital-based monitoring of ovulation? Study protocol of the multicentre, non-inferiority Antarctica-2 randomised controlled trial.

STUDY QUESTION: The objective of this trial is to compare the effectiveness and costs of true natural cycle (true NC-) frozen embryo transfer (FET) using urinary LH tests to modified NC-FET using repeated ultrasound monitoring and ovulation trigger to time FET in the NC. Secondary outcomes are the cancellation rates of FET (ovulation before hCG or no dominant follicle, no ovulation by LH urine test, poor embryo survival), pregnancy outcomes (miscarriage rate, clinical pregnancy rates, multiple ongoing pregnancy rates, live birth rates, costs) and neonatal outcomes (including gestational age, birthweight and sex, congenital abnormalities or diseases of babies born). WHAT IS KNOWN ALREADY: FET is at the heart of modern IVF. To allow implantation of the thawed embryo, the endometrium must be prepared either by exogenous oestrogen and progesterone supplementation (artificial cycle (AC)-FET) or by using the NC to produce endogenous oestradiol before and progesterone after ovulation to time the transfer of the thawed embryo (NC-FET). During an NC-FET, women visit the hospital repeatedly and receive an ovulation trigger to time FET (i.e. modified (m)NC-FET or hospital-based monitoring). From the woman's point of view, a more natural approach using home-based monitoring of the ovulation with LH urine tests to allow a natural ovulation to time FET may be desired (true NC-FET or home-based monitoring). STUDY DESIGN SIZE DURATION: This is a multicentre, non-inferiority prospective randomised controlled trial design. Consenting women will undergo one FET cycle using either true NC-FET or mNC-FET based on randomisation. PARTICIPANTS/MATERIALS SETTING METHODS: Based on our sample size calculation, the study group will consist of 1464 women between 18 and 45 years old who are scheduled for FET. Women with anovulatory cycles, women who need ovulation induction and women with a contra indication for pregnancy will be excluded. The primary outcome is ongoing pregnancy. Secondary outcomes are cancellation rates of FET, pregnancy outcomes (including miscarriage rate, clinical pregnancy, multiple pregnancy rate and live birth rate). Costs will be estimated by counting resource use and calculating unit prices. STUDY FUNDING/COMPETING INTERESTS: The study received a grant from the Dutch Organisation for Health Research and Development (ZonMw 843002807; www.zonmw.nl). ZonMw has no role in the design of the study, collection, analysis, and interpretation of data or writing of the manuscript. F.B. reports personal fees from member of the external advisory board for Merck Serono, grants from Research support grant Merck Serono, outside the submitted work. A.E.P.C. reports and Unrestricted grant of Ferring B.V. to the Center for Reproductive medicine, no personal fee. Author up-to-date on Hyperthecosis. Congress meetings 2019 with Ferring B.V. and Theramex B.V. M.G. reports Department research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the submitted work. E.R.G. reports personal fees from Titus Health Care, outside the submitted work. C.B.L. reports grants from Ferring, grants from Merck, from Guerbet, outside the submitted work. The other authors have none to declare. TRIAL REGISTRATION NUMBER: Dutch Trial Register (Trial NL6414 (NTR6590), https://www.trialregister.nl/). TRIAL REGISTRATION DATE: 23 July 2017. DATE OF FIRST PATIENT'S ENROLMENT: 10 April 2018.

[Bed capacity analysis for an intensive care unit : Retrospective analysis and projection for need of intensive care beds in over 65 year olds with selected cardiovascular diseases]. / Bettenkapazitätsanalyse für eine internistische Intensivstation : Retrospektive Analyse und Projektion des Intensivbettenbedarfs bei über 65-Jährigen mit ausgewählten kardiovaskulären Erkrankungen.

BACKGROUND: The increasing number of elderly individuals in the population and the simultaneous increase of the intensive care demand emphasizes the relevance of an efficient bed capacity analysis. Particularly, cardiovascular diseases represent a frequently occurring disease in the population group over 65 years of age. The objective of the following paper is the analysis of the retrospective and prospective intensive care demand by patients over 65 years with 6 selected (cardiovascular) codes of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). METHODS: For the retrospective analysis, data from 2015-2017 were analyzed applying descriptive and bivariate methods. The analysis of the intensive care bed demand was based on the queuing theory. RESULTS: The monthly capacity utilization rates were constantly higher than the target capacity utilization rate of a maximum of 80% and in some cases even higher than 100%. In particular, the demand of patients with I50.14 was very high throughout the entire hospital. The bed demand analysis shows an increase from 9 needed beds in 2017 to 11 beds by 2030 for the 6 diagnosis groups. Regarding the 5 diagnosis groups without I50.14, only approximately half of the required beds were needed, retrospectively and in future. CONCLUSION: The effect of demographic change on the intensive care demand already exists, and a continuing, prospective increase of the demand is expected. The results underline the need of effective and demand-oriented intensive care capacity planning. However, prior to expanding bed capacities, the analysis of admission criteria of intensive care unit patients is necessary to reserve capacities primarily for patients with real intensive care needs.

Hidradenitis suppurativa is associated with childhood and lifetime traumatic events: a case-control study.

BACKGROUND: Negative life events in childhood can increase the susceptibility to autoimmune and inflammatory diseases. Hidradenitis suppurativa (HS) is a systemic inflammatory disease affecting the apocrine sweat glands, characterized by abscesses, fistulas and inflammatory nodules. It is unknown whether adult HS is associated with traumatic events. OBJECTIVE: To investigate the association between childhood and total lifetime traumatic events and the presence of HS. METHODS: We conducted a matched (1 : 3) case-control study with 71 HS patients and 213 controls. Patients were matched on age, gender and level of education. Questionnaires on general and demographic information, as well as the Traumatic Experience Checklist and the Hospital Anxiety and Depression Scale, were completed. RESULTS: The number of traumatic events (OR: 1.20 per trauma, P value < 0.05), and childhood traumatic events (yes vs. no, OR 3.59, P value < 0.05) and the number of childhood traumatic events (OR 1.35 per trauma, P value < 0.05) were correlated with an increased risk of developing HS. Detailed analysis showed that childhood emotional traumatic events (OR 5.03, P value < 0.05) were significantly associated with the development of HS. CONCLUSION: Number of lifetime traumatic events and childhood traumatic events are associated with HS. This association is strongest for emotional childhood traumas. The increased prevalence of childhood traumas in HS patients can be one of the underlying mechanisms leading to systemic inflammation in these patients.

[Acute iron poisoning : Successful treatment of a potentially fatal suicidal attempt]. / Akute Eisenintoxikation : Erfolgreiche Therapie einer potenziell tödlichen parasuizidalen Geste.

We present the case of a patient who took 150 mg per kg bodyweight of iron in a suicidal attempt. We illustrate the diagnostic and therapeutic procedures required to successfully cope with this poisoning, which is, by surprise, potentially lethal.

Exercise-based cardiac rehabilitation in patients with reduced left ventricular ejection fraction: The Cardiac Rehabilitation Outcome Study in Heart Failure (CROS-HF): A systematic review and meta-analysis.

BACKGROUND: In heart failure with reduced left ventricular ejection fraction (HFrEF) patients the effects of exercise-based cardiac rehabilitation on top of state-of-the-art pharmacological and device therapy on mortality, hospitalization, exercise capacity and quality-of-life are not well established. DESIGN: The design of this study involved a structured review and meta-analysis. METHODS: Evaluation of randomised controlled trials of exercise-based cardiac rehabilitation in HFrEF-patients with left ventricular ejection fraction ≤40% of any aetiology with a follow-up of ≥6 months published in 1999 or later. RESULTS: Out of 12,229 abstracts, 25 randomised controlled trials including 4481 HFrEF-patients were included in the final evaluation. Heterogeneity in study population, study design and exercise-based cardiac rehabilitation-intervention was evident. No significant difference in the effect of exercise-based cardiac rehabilitation on mortality compared to control-group was found (hazard ratio 0.75, 95% confidence interval 0.39-1.41, four studies; 12-months follow-up: relative risk 1.29, 95% confidence interval 0.66-2.49, eight studies; six-months follow-up: relative risk 0.91, 95% confidence interval 0.26-3.16, seven studies). In addition there was no significant difference between the groups with respect to 'hospitalization-for-any-reason' (12-months follow-up: relative risk 0.79, 95% confidence interval 0.41-1.53, four studies), or 'hospitalization-due-to-heart-failure' (12-months follow-up: relative risk 0.59, 95% confidence interval 0.12-2.91, four studies; six-months follow-up: relative risk 0.84, 95% confidence interval 0.07-9.71, three studies). All studies show improvement of exercise capacity. Participation in exercise-based cardiac rehabilitation significantly improved quality-of-life as evaluated with the Kansas City Cardiomyopathy Questionnaire: (six-months follow-up: mean difference 1.94, 95% confidence interval 0.35-3.56, two studies), but no significant results emerged for quality-of-life measured by the Minnesota Living with Heart Failure Questionnaire (nine-months or more follow-up: mean difference -4.19, 95% confidence interval -10.51-2.12, seven studies; six-months follow-up: mean difference -5.97, 95% confidence interval -16.17-4.23, four studies). CONCLUSION: No association between exercise-based cardiac rehabilitation and mortality or hospitalisation could be observed in HFrEF patients but exercise-based cardiac rehabilitation is likely to improve exercise capacity and quality of life.

Lung protective ventilation and hospital survival of cardiac intensive care patients.

OBJECTIVE: To detect connections between parameters of ventilation and outcomes of cardiac intensive care patients. DESIGN AND SETTING: Noninterventional study. Between 05/11 and 05/12 all patients with acute heart failure and post cardiopulmonary resuscitation were registered. Lung protective ventilation was defined as peak inspiratory pressure (PIP) < 30 mmHg and tidal volume (Vt) < = 6 ml/kg. RESULTS: In total, 129 patients were included in the study, 68.2 % male, age 67.9 ± 13.4 years, weight 71.4 ± 37.2 kg, predictive body weight 66.9 ± 8.8 kg, mortality 47.3 %. Lung protective ventilated patients at day 1: 17.3 % with a significant difference between surviving and nonsurviving patients (24.1 % vs. 9.6 %; p < 0.05). Logistic regression models showed a strong connection between PIP and survival (odds ratio 1.13; p < 0.05). Vt showed no significant influence on survival. CONCLUSION: Our data recommends a strict observance of a low PIP for cardiac intensive care patients, whereas Vt seems to be of secondary importance.

Inter-hospital transfer of ECMO-assisted patients with a portable miniaturized ECMO device: 4 years of experience.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) in patients with severe pulmonary failure is able to keep patients alive until organ regeneration, until shunting out for further diagnostic and therapeutic options or until transportation to specialized centers. Nonetheless, extracorporeal techniques require a high degree of expertise, so that a confinement to specialized centers is meaningful. Following from this requirement, the need for inter-hospital transfer of patients with severely compromised pulmonary function is rising. METHODS: We report about our experience with a portable ECMO system during inter-hospital air or ground transfer of patients with cardiopulmonary failure. RESULTS: The portable ECMO system was used for transportation to the center and in-hospital treatment in 36 patients with an average age of 53 years suffering from respiratory failure. Accordingly, the ECMO system was implanted as a veno-venous extracorporeal system. Pre-ECMO ventilation time was 5.2 (2-9) days. Twelve patients were transported to our institution by ground and 24 patients by air ambulance over a median distance of 46 km. With the assistance of the ECMO device, prompt stabilization of cardiopulmonary function could be achieved in all patients without any technical complications. Post-ECMO ventilation was 9.8 days. Weaning from the ECMO system was successful in 61% of all patients after a median device working period of 12.7 days; median ICU stay was 34 days and a survival rate of 64% of patients was achieved. Technical (8%) and device-associated bleeding (11%)/thromboembolic (8%) complication rates showed very acceptable levels. CONCLUSION: Our experience demonstrates that miniaturized, portable ECMO therapy allows location-independent, out-of-center stabilization of pulmonary compromised patients with consecutive inter-hospital transfer and further in-house treatment, so that sophisticated ECMO therapy can be offered to every patient, even in hospitals with primary healthcare.

The Year in Cardiology 2013: cardiovascular disease prevention.

The decline in cardiovascular mortality in Europe by nearly 50% over the last three decades resulted in particular from improved risk factor control and prevention interventions in addition to improved treatment. This review provides an overview of key studies in epidemiology, hypertension control, lipidology, diabetology, and lifestyle changes published in 2013. EXAMINE in diabetology and AIM-High and HPS-2-THRIVE in lipidology failed to demonstrate an event reduction. According to EUROASPIRE IV clinical implementation of secondary prevention treatments is still suboptimal. The 2013 study highlights in prevention prove the dynamic progress of knowledge in the field;, however, knowledge alone is futile without implementation.

Gaze is driven by an internal goal trajectory in a visuomotor task.

When we make hand movements to visual targets, gaze usually leads hand position by a series of saccades to task-relevant locations. Recent research suggests that the slow smooth pursuit eye movement system may interact with the saccadic system in complex tasks, suggesting that the smooth pursuit system can receive non-retinal input. We hypothesise that a combination of saccades and smooth pursuit guides the hand movements towards a goal in a complex environment, using an internal representation of future trajectories as input to the visuomotor system. This would imply that smooth pursuit leads hand position, which is remarkable, as the general idea is that smooth pursuit is driven by retinal slip. To test this hypothesis, we designed a video-game task in which human subjects used their thumbs to move two cursors to a common goal position while avoiding stationary obstacles. We found that gaze led the cursors by a series of saccades interleaved with ocular fixation or pursuit. Smooth pursuit was correlated with neither cursor position nor cursor velocity. We conclude that a combination of fast and slow eye movements, driven by an internal goal instead of a retinal goal, led the cursor movements, and that both saccades and pursuit are driven by an internal representation of future trajectories of the hand. The lead distance of gaze relative to the hand may reflect a compromise between exploring future hand (cursor) paths and verifying that the cursors move along the desired paths.

Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR. Part II.

In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose­response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.

[Prevention of coronary artery disease]. / Prävention der koronaren Herzerkrankung.

Coronary artery disease is still the leading cause of premature death, reduction in physical work capacity and diminished quality of life in western civilizations. Given the fact that coronary artery disease is a preventable disease in most of the cases, its prevalence remains unacceptably high. Consequent application of preventive recommendations with regards to life-style aspects like tobacco use, nutrition, overweight and physical activity could help to reduce the prevalence of atherosclerotic diseases by half. Aim of this review is to focus the reader's attention to the most important risk factors, their influence on progression of atherosclerotic lesions and ways to reduce risk factor burden.

[Acute colitis in Wegener's disease: a case report]. / Colite aiguë révélant une maladie de Wegener.

We report the case of a 52 year old man who was hospitalized within a context of a persistent deterioration of his general condition. He was suspected of having a chronic inflammatory colitis. A pulmonary radiography revealed the presence of voluminous bilateral excavated masses with hydro-aerical levels. After having refuted among others a suspicion of tuberculosis, the results of a thoracic percutaneous transpleural lung aspiration by needle under tomodensitometric control steered our diagnosis towards a vascularitis of the Wegener disease type. A treatment with corticotherapy in large doses completed with cyclophosphamid allowed for clinical, biological and radiological improvement. Wegener's granulomatosis usually starts in an insidious manner with febrile episodes and an impairment of the general condition associated with inflammatory biological signs, as observed in our patient. After these warning symptoms, come ORL and/or pulmonary and/or renal impairment, which represent the classical triad of diffused GW. However a certain number of particularities unusual for that diagnosis characterized our patient and prompted the discussion of this case.

Growth regulation and transcriptional activities of estrogen and progesterone in human endometrial cancer cells.

Estrogen-stimulated growth of the malignant human endometrium can be balanced by the differentiating properties of progesterone. To study the molecular basis behind this, gene expression profiling was performed using complementary DNA microarray analysis. In this study, the human endometrial cancer cell lines ECC-1 and PRAB-36 were used as models. The ECC-1 cell line, which expresses high levels of estrogen receptor alpha and is stimulated in growth by estrogens, was used to study estrogen regulation of gene expression. The Ishikawa sub-cell line PRAB-36, expressing both PRA and PRB, progesterone receptor isoforms, and inhibited in growth by progestagens, was used to study progesterone regulation of gene expression. Using these two well-differentiated human endometrial cancer cell lines, 148 estrogen- and 148 progesterone-regulated genes were identified. After functional classification, the estrogen- and progesterone-regulated genes could be categorized in different biologically relevant groups. Within the group of "cell growth and/or maintenance," 81 genes were clustered, from which a number of genes could be involved in arranging the cross talk that exists between estrogen and progesterone signaling. On the basis of analysis of the current findings, it is hypothesized that cross talk between estrogen and progestagen signaling does not occur by counterregulation of single genes, but rather at the level of differential regulation of different genes within the same functional families.

Phytotoxicity of tolylfluanid in tomatoes.

The use of Euparen Multi (tolylfluanid) for controlling Botrytis cinerea in tomatoes has been decreased the last decade for several reasons. Because of the lack of different fungicides with a good efficacy it is important that growers can use different fungicides to prevent development of resistance of Botrytis cinerea against many fungicides. Tolylfluanid has negative side effects on some insect populations that are used for biological control. It is known that Euparen Multi and Euparen can have a negative effect on some predatory mites (Schmidt and Zeller, 1998) such as Phytoseiulus persimilis and some parasitic wasps like Encarsia formosa, Eretmocerus eremicus, Diglyphus isaea and Dacnusa sibirica. Recently investigation indicates that this fungicide is harmless for the predatory bug Macrolophus caliginosus (Biobest, 2006) frequently used in the cultivation of tomatoes as a predator for whitefly (Trialeurodes vaporariorum). To investigate if tolylfluanid has a phytotoxic effect on tomato plants an experiment was performed. Young tomato plants were used, who are more sensitive. These plants were subdivided in different groups, from which each one was sprayed with a different concentration of tolylfluanid. The highest concentrations of tolylfluanid were used to stimulate the visibility of the possible phytotoxic effects. Results of this experiment demonstrate that there wasn't a difference between the different groups that were sprayed with tolylfluanid or the control group. This indicates that tolylfluanid doesn't seem to be phytotoxic. It is also important to mention that this experiment was done in the fall when the intensity of the sunlight was decreasing. There still exists the possibility that extreme irradiation in combination with tolylfluanid can provoke a phototoxic effect on young tomato plants.

Tamoxifen treatment for breast cancer enforces a distinct gene-expression profile on the human endometrium: an exploratory study.

Tamoxifen treatment for breast cancer increases proliferation of the endometrium, resulting in an enhanced prevalence of endometrial pathologies, including endometrial cancer. An exploratory study was performed to begin to understand the molecular mechanism of tamoxifen action in the endometrium. Gene-expression profiles were generated of endometrial samples of tamoxifen users and compared with matched controls. The pathological classification of samples from both groups included atrophic/inactive endometrium and endometrial polyps. Unsupervised clustering revealed that samples of tamoxifen users were, irrespective of pathological classification, fairly similar and consequently form a subgroup distinct from the matched controls. Using SAM analysis (a statistical method to select genes differentially expressed between groups), 256 differentially expressed genes were selected between the tamoxifen and control groups. Upon comparing these genes with oestrogen-regulated genes, identified under similar circumstances, 95% of the differentially expressed genes turned out to be tamoxifen-specific. Finally, construction of a gene-expression network of the differentially expressed genes revealed that 69 genes centred around five well-known genes: TP53, RELA, MYC, epidermal growth factor receptor and beta-catenin. This could indicate that these well-known genes, and the pathways in which they function, are important for tamoxifen-controlled proliferation of the endometrium.

[Effects of physical training of chronic cardiac insuffciency]. / Grundlegender Wandel in der Therapie der chronischen Herzinsuffizienz: Vom Sessel auf das Laufband!

During the last ten years,the traditional dogma "physical rest" for patients with chronic cardiac insufficiency (CCI) has been increasingly abandoned. Studies on the effects of low intensity physical endurance training for patients with stable CCI showed the following effects after 12 months: Decrease in the heart size and a slight improvement in the EF, reduction of the systemic vascular resistance during rest and during stress through improvement of the endothelial function, increase in the physical performance by 12 to 26%, reduction of local inflammation and improvement of the oxidative metabolism in skeletal muscles, an end to muscle atrophy and reduction of the total mortality. Training programs for patients with chronic cardiac insufficiency today represent an established auxiliary therapy for CCI with prognostic relevance.

[Physical exercise in older patients with chronic heart failure]. / Körperliche Aktivität bei älteren Patienten mit chronischer Herzinsuffizienz.

Maximal exercise capacity undergoes a steady decline after the age of 30 by approximately 10 % per decade. As a consequence of this development older people > 65 years of age suffer from the exercise limitation caused by age-associated cardiac, vascular and skeletal muscle changes. These physiologic alterations make older people especially vulnerable for the cardiovascular and peripheral alterations associated with chronic heart failure (CHF). These changes are not phenomenologically different from age-associated changes. Physical activity plays an important role for regaining a considerable part of vasomotor function, skeletal muscle contractility, and cardiac reserve. Up to now there are no prospective trials comparing the effects of physical training between older and younger patients with CHF. However, smaller observational studies indicate that elderly patients benefit equally well from training interventions with regard to functional improvements in proportion to their lower baseline values. In an aging population training aims at maintaining skeletal muscle force and muscle mass as well as locomotor coordination. Ultimately, the goal is to reduce the substantial morbidity among elderly CHF patients which constitute 79 % of all hospital admissions for heart failure.