Changes in anticoagulant prescription in Dutch patients with recent-onset atrial fibrillation: observations from the GARFIELD-AF registry.

BACKGROUND: For the improvement of AF care, it is important to gain insight into current anticoagulation prescription practices and guideline adherence. This report focuses on the largest Dutch subset of AF-patients, derived from the GARFIELD-AF registry. METHODS: Across 35 countries worldwide, patients with newly diagnosed 'non-valvular' atrial fibrillation (AF) with at least one additional risk factor for stroke were included. Dutch patients were enrolled in five, independent, consecutive cohorts from 2010 until 2016. RESULTS: In the Netherlands, 1189 AF-patients were enrolled. The prescription of non-vitamin K antagonist oral anticoagulants (NOAC) has increased sharply, and as per 2016, more patients were initiated on NOACs instead of vitamin K antagonists (VKA). In patients with a class I recommendation for anticoagulation, only 7.5% compared to 30.0% globally received no anticoagulation. Reasons for withholding anticoagulation in these patients were unfortunately often unclear. CONCLUSIONS: The data from the GARFIELD-AF registry shows the rapidly changing anticoagulation preference of Dutch physicians in newly diagnosed AF. Adherence to European AF guidelines in terms of anticoagulant regimen would appear to be appropriate. In absence of structured follow up of AF patients on NOAC, the impact of these rapid practice changes in anticoagulation prescription in the Netherlands remains to be established.

In Vivo Analysis of NH4+ Transport and Central Nitrogen Metabolism in Saccharomyces cerevisiae during Aerobic Nitrogen-Limited Growth.

Ammonium is the most common N source for yeast fermentations. Although its transport and assimilation mechanisms are well documented, there have been only a few attempts to measure the in vivo intracellular concentration of ammonium and assess its impact on gene expression. Using an isotope dilution mass spectrometry (IDMS)-based method, we were able to measure the intracellular ammonium concentration in N-limited aerobic chemostat cultivations using three different N sources (ammonium, urea, and glutamate) at the same growth rate (0.05 h-1). The experimental results suggest that, at this growth rate, a similar concentration of intracellular (IC) ammonium, about 3.6 mmol NH4+/literIC, is required to supply the reactions in the central N metabolism, independent of the N source. Based on the experimental results and different assumptions, the vacuolar and cytosolic ammonium concentrations were estimated. Furthermore, we identified a futile cycle caused by NH3 leakage into the extracellular space, which can cost up to 30% of the ATP production of the cell under N-limited conditions, and a futile redox cycle between Gdh1 and Gdh2 reactions. Finally, using shotgun proteomics with protein expression determined relative to a labeled reference, differences between the various environmental conditions were identified and correlated with previously identified N compound-sensing mechanisms.IMPORTANCE In our work, we studied central N metabolism using quantitative approaches. First, intracellular ammonium was measured under different N sources. The results suggest that Saccharomyces cerevisiae cells maintain a constant NH4+ concentration (around 3 mmol NH4+/literIC), independent of the applied nitrogen source. We hypothesize that this amount of intracellular ammonium is required to obtain sufficient thermodynamic driving force. Furthermore, our calculations based on thermodynamic analysis of the transport mechanisms of ammonium suggest that ammonium is not equally distributed, indicating a high degree of compartmentalization in the vacuole. Additionally, metabolomic analysis results were used to calculate the thermodynamic driving forces in the central N metabolism reactions, revealing that the main reactions in the central N metabolism are far from equilibrium. Using proteomics approaches, we were able to identify major changes, not only in N metabolism, but also in C metabolism and regulation.

Acceptance and commitment therapy as guided self-help for psychological distress and positive mental health: a randomized controlled trial.

BACKGROUND: In order to reduce the high prevalence of depression, early interventions for people at risk of depression are warranted. This study evaluated the effectiveness of an early guided self-help programme based on acceptance and commitment therapy (ACT) for reducing depressive symptomatology. METHOD: Participants with mild to moderate depressive symptomatology were recruited from the general population and randomized to the self-help programme with extensive email support (n=125), the self-help programme with minimal email support (n=125) or to a waiting list control group (n=126). Participants completed measures before and after the intervention to assess depression, anxiety, fatigue, experiential avoidance, positive mental health and mindfulness. Participants in the experimental conditions also completed these measures at a 3-month follow-up. RESULTS: In the experimental conditions significant reductions in depression, anxiety, fatigue, experiential avoidance and improvements in positive mental health and mindfulness were found, compared with the waiting list condition (effect sizes Cohen's d=0.51-1.00). These effects were sustained at the 3-month follow-up. There were no significant differences between the experimental conditions on the outcome measures. CONCLUSIONS: The ACT-based self-help programme with minimal email support is effective for people with mild to moderate depressive symptomatology.

Evidence of Mycobacterium avium subsp. paratuberculosis infection in Dutch farmed red deer.

Paratuberculosis is a chronic disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Most economic losses due to MAP occur in the dairy industry. However, the infection is not restricted to cattle, but also occurs in other ruminants, such as sheep, goat, and deer. Although deer are of minimal economic importance in The Netherlands, they may constitute a source of infection for the dairy industry. This pilot study was conducted to estimate the prevalence of Johne's disease in farmed red deer in The Netherlands. Serum and faecal samples were collected from 140 animals, originating from 8 different farms. Four of the farms had animals that tested positive for Johne's disease. The within-herd MAP seroprevalence varied between 4.8% and 21.2%. In conclusion, this pilot study provides evidence of MAP infection in the Dutch farmed deer population, and thus there might be a risk of MAP transmission between farmed red deer and dairy cattle.

Stress-reducing effects of indoor plants in the built healthcare environment: the mediating role of perceived attractiveness.

OBJECTIVE: Natural elements in the built healthcare environment have shown to hold potential stress-reducing properties. In order to shed light on the underlying mechanism of stress-reducing effects of nature, the present study investigates whether the stress-reducing effects of indoor plants occur because such an environment is perceived as being more attractive. METHOD: A single-factor between-subjects experimental design (nature: indoor plants vs. no plants) was used in which participants (n=77) were presented with a scenario describing hospitalization with a possible legionella diagnosis. The study was conducted from March to May 2007 in the Netherlands. Subsequently, they were exposed to a photo of a hospital room. In this room were either indoor plants, or there was a painting of an urban environment on the wall. Afterwards, perceived stress and the perceived attractiveness of the hospital room were measured. RESULTS: Participants exposed to the hospital room with indoor plants reported less stress than those in the control condition. Mediation analysis confirmed that indoor plants in a hospital room reduce feelings of stress through the perceived attractiveness of the room. CONCLUSION: This study confirms the stress-reducing properties of natural elements in the built healthcare environment. It also sheds light on the underlying mechanism causing this stress-reduction.

Effectiveness of a minimal contact smoking cessation program for Dutch general practitioners: a randomized controlled trial.

BACKGROUND: Until recently, Dutch general practitioners contributed little to tobacco control. This is due to several factors, among which is the lack of a feasible intervention program for adult smokers. Such a minimal contact behavioral intervention, using the Stage-of-Change concept, is now available. Effectiveness was tested in a randomized trial. METHOD: Twenty-two general practitioners and their practice assistants were trained in applying the program. In all, 530 smoking patients were enrolled, randomly assigned to either the intervention or the usual treatment condition. Analysis of treatment effects was performed with logistic regression analysis. In a backward stepwise procedure confounding effects of baseline differences were eliminated. RESULTS: At 12-month follow-up, self-reported abstinence rates (including nonrespondents as smokers) differed significantly between intervention subjects and controls: 13.4 vs 7.3% point prevalence (odds ratio 1.51, P < 0.05). An analysis of consecutive abstinence, defined as being abstinent at both 6- and 12-month follow-up, showed that 8.2% of the intervention group compared to 3.1% of the controls had sustained abstinence for more than 6 months (odds ratio 3.04, P < 0.001). CONCLUSIONS: Results indicate that an effective smoking cessation program for use in Dutch general practice, already shown to be feasible, is now available. Outcomes are generally consistent with recent international literature.

Relative accuracy of the identification of ovarian structures in the cow by ultrasonography and palpation per rectum.

Manual palpation or ultrasonographic examination of the cow's genital tract are currently used by veterinarians involved in reproductive management, but knowledge of the potential and the limitations of both methods is important to obtain an optimal accuracy in the diagnosis of physiological and pathological ovarian structures. This review presents the main features of manual and ultrasonographic characteristics of follicles, corpora lutea (with or without a cavity), follicular and lutenized cysts and the reliability of the two methods is compared. Manual diagnosis of follicles <10 mm is rather inaccurate, but ultrasound offers the possibility to diagnose follicles <5 mm and to measure their inner diameter. The predictive values of the presence or absence of a corpus luteum as determined by palpation are similar (78 vs. 75%). Manual or ultrasonographic diagnosis of the growing or regressing corpus luteum is rather difficult. The positive predictive value of a mature corpus luteum diagnosed by ultrasonography is lower (87%) than the negative predictive value (92%). Compared to manual palpation, ultrasonography permits a better estimation of the number and to determine more precisely the size of the mature corpus luteum. The positive values for follicular cysts diagnosed by palpation or by ultrasonography are 66 and 74% respectively, and for luteal cysts, the values are 66 and 85%, respectively.Manual palpation or ultrasonography are useful tools to diagnose ovarian structures in the cow. The accuracy of such methods can be enhanced by securing information on the reproductive history of the animal, palpation of uterine horns, vaginal examination or progesterone determinations.

Follicular dynamics, repeatability and predictability of follicular recruitment in cows undergoing repeated follicular puncture.

The aim of our study was to characterize follicular recruitment and growth in response to the repeated removal of follicles. All tertiary follicles (> 2 mm of diameter) in the ovaries of 10 non-lactating Holstein Friesian cows were punctured at midcycle (Day 0) by means of an ultrasound-guided needle. Puncture sessions were scheduled twice weekly at 3- or 4-d intervals over 3 mo. In the middle of the experiment, i.e., Week 7, the effects of 2- and 5-d intervals between follicular punctures were tested and compared with the previous 3- and 4-d intervals. After this period, 6 animals were slaughtered to study the effect of puncturing on gross ovarian morphology. The protocol of puncturing follicles with 3- to 4-d intervals was continued for an additional 3 mo in the remaining 4 animals. Twice-weekly puncturing of all tertiary follicles abolished estrous cycles and lead to an increase in follicular wave frequency without apparent negative effects on either the reproductive tract or ovaries. After puncture the new follicular wave attained full numerical development within 3 d. Two-day intervals resulted in a lower number of follicles than the 3-d interval (11.0 -/+ 3.8 vs 15.4 -/+ 6.1; P < 0.05). In contrast 4- and 5-d intervals between puncture resulted in an increase in follicle size when compared with that of the 3-d interval. The mean+SD number of recruited follicles varied between animals ranging between 78 +/- 2.5 to 19.2 -/+ 6.0. The mean number of follicles recruited increased from the first month (March) to the third month (May) of sampling (11.8 +/- 4.7 vs 16.4 +/- 6.5; P < 0.01), and then decreased between the third (May) and the sixth (August) month of sampling (21.5 +/- 4.7 vs 16.8 +/- 5.0; P < 0.01). During the experiment, the number of recruited follicles varied cyclically, with waves having a length of 6 puncture session (PS) or 3 wk (i.e., the mean length the bovine estrous cycle). Follicular recruitment after repeated ovum pick-up showed a high repeatability (r = 0.576) A model was also developed showing good predictability of the potential of animals to recruit follicles on the basis of the first 4 to 6 PS. Our results showed that despite large variation in follicular recruitment between animals, the high repeatability and good predictability of follicle recruitment demonstrates the possibility of characterizing animals on their potential for follicle growth.

Transvaginal interstitial laser treatment of the ovary: a feasibility study in cows.

In 12 cows, transvaginal interstitial laser treatment (TILT) of the ovaries was performed using a neodynium:yttrium aluminium-garnet laser to investigate the feasibility of a new treatment approach for clomiphene-resistant patients with chronic hyperandrogenic anovulation. Powers of 1 and 2 W during 5 min of exposure were used. Sonographic changes of thermal damage during TILT, the extent and healing of the lesions by light microscopy and ultrasound during 3 month follow-up and adhesion formation were studied. During laser irradiation, a hyperechogenic zone developed around the fibre tip, with a mean +/- SD diameter of 4.4 +/- 2.0 mm at 1 W and 6.9 +/- 1.5 mm at 2. W. The mean diameters of the histological lesions 2 days after treatment were 7.3 +/- 2.5 mm at 1 W and 13.0 +/- 2.1 mm at 2 W. During follow-up, the mean diameter of both the histologically and the sonographically assessed lesions decreased, although transvaginal sonography (TVS) systematically and significantly underestimated the thermal damage. Lesions healed by fibrosis and no adhesions were present. TILT of the ovaries in cows is easy to perform and produces central or subcapsular necrosis without adhesions. TVS gives an indication of thermal damage but underestimates the extent of tissue damage in cow ovaries. Obviously, this study does not allow conclusions to be drawn concerning its safety and efficacy in man.

[Dehorning of goats and kids]. / Het onthoornen van geiten en geitelammeren.

The local anaesthesia used during the dehorning of goats is described. The authors recommend general anaesthesia for the disbudding (dehorning) of kids. In addition to the dehorning of goats and kids, this article also describes the use of the combination of xylazine, ketamine, and atropine, and the preparation of this 'goat anaesthetic'.

Initial experience with mode switching in a dual sensor, dual chamber pacemaker in patients with paroxysmal atrial tachyarrhythmias.

Mode switching algorithms have been developed to avoid tracking of atrial fibrillation (AF) or flutter (AFL) during DDD(R) pacing. Upon recognition of AF or AFL, the mode is switched to a nontracking, sensor driven mode. The Vitatron Diamond model 800 pacemaker does this on a beat-to-beat basis. Atrial events occurring within a "physiological range" (+/- 15 beats/min) calculated from a running average of the atrial rate are tracked. When atrial events are not tracked the escape interval is either determined by the sensor(s) or by a fallback algorithm thereby preventing large increases in V-V interval during mode switching. Loss of atrioventricular (AV) synchrony by atrial premature beats and after an episode of AF or AFL is prevented by atrial synchronization pulses (ASP), which are delivered after a safe interval (timed out from the sensed premature atrial event) has expired and before delivery of the next ventricular stimulus. We implanted 26 such devices in 18 men and 8 women with symptomatic second- or third-degree AV block and paroxysmal AF or AFL. Their ages ranged from 18-84 years (mean 60), and the follow-up ranged from 2-13 months (mean 8). During pacemaker check-up, exercise testing or 24-hour Holter monitoring one or more episodes of mode switching was documented in 8 patients. In these 8 patients a smooth transition (ventricular rate) from sinus rhythm to AF or AFL was documented on one or more occasions, without inappropriate increase in ventricular rate in the DDDR mode. None of the patients complained of palpitations.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential use of ovum pick-up for embryo production and breeding in cattle.

The efficacy of transvaginal ultrasound-guided puncturing of ovarian follicles for collecting immature oocytes in cattle was studied. Three experiments were conducted to examine the effects of puncturing on follicle recruitment and on the number of oocytes collected. Puncture sessions were executed twice weekly at regular intervals of 3 and 4 d respectively. The oocytes were matured, fertilized and allowed to develop in vitro and the number of transferable embryos was recorded. The health of the cows was checked daily. In Experiment 1, dairy cows (n=10) were punctured over a period of 5 mo, and the collected oocytes were fertilized with the semen of 1 bull. In Experiment 2, oocytes were collected from one 12 year old high pedigree dairy cow and an one month pregnant cow were punctured. The oocytes of the old cow were fertilized with semen of 8 different bulls. In Experiment 3, beef cows (n=6) were punctured over a 2 mo period and the semen of 2 different bulls of the same breed was used to fertilize the oocytes from 3 of these cows. In Experiment 1, 14.5 +/- 0.4 (mean +/- SEM) follicles were punctured per session, and 8.0 +/- 0.3 (mean +/- SEM) oocytes were recovered. A mean of 16% of the oocytes developed into transferable embryos with a pregnancy rate of 40%. The results did not differ between the months of the experiments, indicating that the transvaginal puncturing method can be used successfully over a 5 mo period. No detrimental effects were observed after clinical and post mortem examinations, nor did breed, age or reproductive status appear to affect the results. However, large differences were observed between individual cows and between cow/bull combinations.

[Possibilities of ovum pickup in cattle]. / Mogelijkheden van ovum pick-up bij het rund.

Cattle breeding has a new reproduction technique in addition to artificial insemination and embryo transfer. It is the collection of ova from living animal by means of ultrasound guided follicle aspiration (ovum pick-up), followed by embryo-production in vitro. Follicles larger than 2 mm were punctured and the ova were collected twice weekly during 3 months. In total 1677 ova were collected from ten cows; 1342 (80%) were used for in vitro maturation, fertilization, and embryoculture. All ova were fertilized with semen from one bull, and 218 transferable embryos were produced. Calculated on a year basis, this would amount to 87 embryos per animal, with an intra-animal variation between 28 and 132. This new technique may replace MOET (Multiple Ovulation and Embryo Transfer; yearly average of 25 transferable embryos per animal), if the embryo-production via OPU can be performed with semen from any selected bull.

Programming a long paced atrioventricular interval may be risky in DDDR pacing.

In patients with intermittent AV block and dual chamber pacemakers, a long paced AV interval of 200 msec or more can be selected to prolong pulse generator life (by avoiding the ventricular pace output) and to enable a more physiological and hemodynamically superior activation sequence. This case report describes the potential risks of programming a long paced AV interval in a patient with a DDDR pacemaker. T wave pacing, as described here, can occur if the conducted QRS complex is not sensed because it occurs during the ventricular blanking period (delivery of the atrial stimulus). This can be initiated by the mechanisms that induce apparent and actual P wave undersensing of the conducted QRS complex. In this case report apparent P wave undersensing and subsequent T wave pacing with ventricular capture (in a patient with intermittent AV block) occurred frequently during an exercise test done in the DDDR mode with a paced AV interval of 200 msec, according to the clinical evaluation protocol.

Evaluation of transvaginal ultrasound-guided follicle puncture to collect oocytes and follicular fluids at consecutive times relative to the preovulatory LH surge in eCG/PG-treated cows.

Holstein-Friesian cows (n=56) were synchronized with Syncro-Mate B, and those cows (n=47) developing a normal progesterone pattern were further treated im with 3,000 I.U. eCG at Day 10 and 22.5 mg PGF2alpha 48 h later. Blood samples were collected every hour from 30 until 49 h after PG administration. Cows (n=17, 36.2%) with fewer than 8 follicles larger than 8 mm in diameter at 28 to 30 h after PG treatment and animals without an LH peak (n=7, 23%) were excluded from the study. Transvaginal ultrasound-guided puncture of the follicles was carried out two times per cow, at 30 h after PG injection (4 to 5 follicles) and again at 1 to 5 (n=6), 12 (n=8) or 22 h (n=9) after the LH peak. No differences in the concentrations of progesterone and LH were observed among the 3 groups. An average of 18 follicles per cow was punctured (total of 415 punctures, n=23); 116 cumulus-oocyte-complexes and 370 follicular fluid samples were obtained producing average recovery rates of 28.0% and 89.2%. The number of cumulus-oocyte-complexes varied between puncture times; shortly before ovulation, at 22 h after the LH peak, the recovery rate was significantly 5 times higher than immediately after the LH peak. Overall, in 75 punctures the cumulus-oocyte-complex was accompanied by a pure follicular fluid sample (3.3 per cow). In conclusion, the transvaginal ultrasound-guided puncture of preovulatory-size follicles can be used to collect follicular fluids to study changes in the microenvironment of maturing oocytes upon superovulation. However, further research is required in order to obtain an equivalent number of accompanying cumulus-oocyte-complexes.