Low-dose aspirin prophylaxis to prevent hypertensive disorders of pregnancy after in vitro fertilisation: a scoping review protocol.

INTRODUCTION: Pregnancies resulting from in vitro fertilisation are associated with an increased risk of developing hypertensive disorders of pregnancy, such as preeclampsia, when compared with naturally conceived pregnancies. OBJECTIVE: The efficacy of aspirin prophylaxis to reduce the incidence of preeclampsia is well established in naturally conceived pregnancies identified as high risk for developing preeclampsia. However, the efficacy of aspirin to reduce the rate of preeclampsia for all pregnancies resulting from in vitro fertilisation remains uncertain, although in vitro fertilisation conception is a well-known risk factor for preeclampsia. Therefore, the purpose of this scoping review is to provide a comprehensive overview of the current literature regarding the use of low-dose aspirin to prevent hypertensive disorders of pregnancy after in vitro fertilisation. INCLUSION CRITERIA: This review will identify all peer-reviewed published articles including pregnant women who underwent embryo transfer after in vitro fertilisation and were prescribed low-dose aspirin to reduce the risk of hypertensive disorders of pregnancy. METHODS: We have devised a comprehensive search strategy to systematically identify pertinent studies published from January 2000 until May 2024, within the Medline (PubMed interface), Embase and Scopus databases. The search strategy is based on the keywords 'aspirin,' 'pregnancy-induced hypertension,' and ('in vitro fertilization' OR 'oocyte donation' OR 'embryo transfer' OR 'donor conception'). Two reviewers will independently screen the titles, abstracts and full-text articles to select the relevant articles, using the Covidence software. ETHICS AND DISSEMINATION: No patients are involved in this study. This study aims to be published in a peer-reviewed journal and could be presented at a conference.

[OCEBM levels of evidence system]. / Médecine factuelle: la hiérarchisation des preuves par le Centre for Evidence-Based Medicine d'oOford.

The hierarchy of evidence from medical research is a key concept in evidence-based medicine (EBM). In 1998, the Oxford Centre for Evidence-Based Medicine published a levels table based on study designs. An updated and more user-friendly version, published in 2011, focuses on the issues of prevalence, diagnosis, prognosis, treatment and screening. This paper presents and discusses this approach.

Exercise-induced pulmonary perfusion redistribution in heaves.

This study aimed to compare exercise-induced pulmonary perfusion redistribution in healthy vs. 'heavey' horses using scintigraphy, a minimally invasive technique. Six healthy (A) and 5 'heavey' horses in remission (B(I)) and during clinical signs of disease (B(II)) were investigated. Dimensions of the exercising pulmonary perfusion (QE) images were expressed in percent of the resting perfusion (QR) images. Computed QE to QR ratios (QE/QR) images enabled the definition of the region more perfused at exercise than at rest (R1). In all groups, exercise induced a major enlargement of the Q image but a larger increase of the lung height was found in 'heavey' horses. Compared to A, 'heavey' horses showed a larger R1 region with a significantly higher QE/QR. Location of R1 pointed out the dorsal lung region as a major site of pulmonary perfusion redistribution for all groups. This work demonstrated (1) the feasibility of using scintigraphy for studying exercise-induced pulmonary perfusion redistribution; (2) perfusion redistribution to the dorsal lung with exercise and (3) an intensified redistribution in 'heavey' horses, either clinically affected or not.

The use of cardboard bedding material as part of an environmental control regime for heaves-affected horses: in vitro assessment of airborne dust and aeroallergen concentration and in vivo effects on lung function.

This study aimed to test whether shredded cardboard is an appropriate minimum-dust bedding material for heaves-affected horses. Results of standardized in vitro measurement of airborne dust and aeroallergen concentrations of cardboard bedding were significantly lower than those of common bedding materials. Six heaves-affected horses in clinical remission after pasturing were stabled for two months on cardboard bedding and fed grass silage. Pulmonary function tests (PFT: ventilatory mechanics, arterial blood gases, airway inflammation scoring, bronchoalveolar cytology) were performed before, during and after this period and after stabling the horses in poor hygienic conditions. PFT values measured during and after the stabling period on cardboard bedding were not significantly different from those recorded after the period at pasture or from those of healthy horses, but were significantly different from those recorded in poor hygienic conditions. On basis of the in vitro and in vivo results it can be concluded that cardboard bedding, used in conjunction with low-dust forage, may be appropriate in the provision of minimum-dust management of heaves-affected horses.

Effects of inhaled ipratropium bromide on breathing mechanics and gas exchange in exercising horses with chronic obstructive pulmonary disease.

Six Warmblood horses suffering an acute exacerbation of COPD were tested to investigate whether inhalation of ipratropium bromide (IB) dry powder (2,400 microg) 30 min preexercise would improve their exercise capacity. A cross-over protocol with an inert powder placebo (P) was used. Mechanics of breathing and arterial blood gases were determined before treatment, after treatment but pre-exercise, and during an incremental exercise test. Oxygen consumption (VO2) was also measured before and during exercise, and the time to fatigue recorded. Inhalation of IB reduced total pulmonary resistance (RL) and maximum intrapleural pressure changes (deltaPpl(max)) and increased dynamic compliance before exercise. The onset of exercise was associated with a marked decrease in RL in P-treated horses but not those receiving IB, so that RL during exercise was not affected by treatment. Although deltaPpl(max) was lower at 8,9 and 10 m/s with IB, there were no treatment-related changes in VO2, blood gases, time to fatigue or any other measurement of breathing mechanics. Therefore, although inhalation of IB prior to exercise may have improved deltaPpl(max), it had no apparent impact on the horses' capacity for exercise.

Alveolar clearance in horses with chronic obstructive pulmonary disease.

OBJECTIVE: To assess sensitivity of scintigraphic alveolar clearance rate as an indicator of alveolar epithelium damage in horses. ANIMALS: 5 healthy horses (group A) and 5 with chronic obstructive pulmonary disease (COPD; group B). PROCEDURE: Horses underwent clearance rate (k [%/min]) determination. Clearance rate of group-B horses was determined after remission of the disease following 2 months at pasture (remission 1), stabling in a controlled environment (remission 2), and during crisis induced by exposure to moldy hay and straw. Methacholine challenge test was performed at each investigation period to determine nonspecific pulmonary airway hyperresponsiveness. Pulmonary function tests (PFT) also were performed, and cell populations in bronchoalveolar lavage (BAL) fluid were determined on another occasion. RESULTS: Group-B horses had significantly faster mean clearance rate during crisis (k = 4.30+/-0.95%/min), compared with that for remission 1(k = 1.98+/-0.55%/min), which did not differ from the rate in group-A horses (k = 1.95+/-0.33%/min). Despite lack of clinical signs of COPD during remission when stabled in a controlled environment, an intermediate value was found (k = 3.20+/-0.72%/min). CONCLUSIONS: This technique allowed grading of lung damage induced by COPD, whereas use of PFT and determination of BAL fluid cell populations failed to differentiate between remission 1 and remission 2. CLINICAL RELEVANCE: Determination of alveolar clearance rate by use of scintigraphy is a sensitive indicator of lung damage. A modified clearance rate was found despite the lack of clinical and functional changes.

Analysis of scintigraphical lung images before and after treatment of horses suffering from chronic pulmonary disease.

Scintigraphical analysis of the ratio of inhalation (I) to perfusion (Q) was designed to determine whether chronic pulmonary disease in horses induced mismatches in I/Q and to assess whether medical treatment would restore an I/Q distribution pattern identical to that of control horses. In addition, the results of the I/Q analysis were correlated with the alveolar-arterial PO2 difference (AaDO2). The I/Q matching found in a group of control horses was compared with the I/Q analysis of a group of diseased horses before and after their clinical signs had been treated. The analysis indicated that there was mismatching between I and Q before they were treated. The treatment improved the diseased horses, pulmonary function but there was still heterogeneity in the I/Q distribution after they had been treated. The I/Q analysis parameters were well correlated with the ratio of ventilation (VA) and pulmonary blood flow (Q), evaluated by the determination of AaDO2.

Effects of inhaled dry powder ipratropium bromide on recovery from exercise of horses with COPD.

The present study evaluated ventilatory, cardiovascular and metabolic parameters during recovery from strenuous exercise in horses suffering from a crisis of chronic obstructive pulmonary disease (COPD) and to determine whether ipratropium dry powder inhalation (DPI) before exercise has an effect on these parameters. When 6 saddle horses, affected with COPD, developed airway obstruction, they inhaled placebo and ipratropium (2400 microg/horse), the order being randomly chosen. Pulmonary function tests were then recorded 15 min after inhalation. Following these tests, the horses underwent a strenuous treadmill exercise, followed by a recovery period that consisted of a 10 min walk. Measurements were made at the first and tenth min of recovery. Respiratory flow, O2 and CO2 fractions in the respired gas, pleural pressure changes and heart rate were recorded. Arterial and mixed venous blood samples were analysed for gas tensions, haemoglobin and plasma lactate concentrations. Oxygen consumption (VO2), CO2 production, tidal volume, alveolar oxygen tension (PAO2), alveolar ventilation, the alveolar-pulmonary capillary oxygen difference ((A-a)dO2) and total pulmonary resistance (RL) were measured. The PAO2 was the only parameter significantly improved during recovery following ipratropium DPI. This improvement was not accompanied by evidence of improvement of other ventilatory or cardiorespiratory parameters. The results showed that in horses suffering from a crisis of COPD, recovery is characterised by an exercise-induced bronchodilation. Secondly, ipratropium DPI at a dose of 2400 microg/horse is an effective bronchodilator in these horses at rest but it has little effect on the airway calibre during the recovery period. It is suggested that the short term recovery period is still influenced by exercise-induced adjustments that may exceed the bronchodilatory effect of inhaled ipratropium that are observed before exercise.

Scintigraphical evaluation of alveolar clearance in horses.

This study proposed a standardized method for measuring alveolar epithelium membrane permeability in the horse. The normal rate of clearance (%.min-1) from lung into blood of nebulized 99mTc-DTPA has been established for healthy horses (Group A) compared with values obtained with horses suffering from chronic obstructive pulmonary disease (COPD; Group B). The 99mTc-DTPA clearance was measured in the caudoventral (R1) and in the half caudal (R2) parts of the left lung during different time intervals. The two regions aimed to define the influence of the airways on measured clearance (R2 contained proportionally more conducting airways than R1). It was concluded that a comparison of groups of subjects may be performed in R2 and on data collected during a 20 min period. The normal clearance rate in R2 was 1.80 +/- 0.46%.min-1 (T1/2R2 = 40.99 +/- 12.45 min) in Group A. In Group B, a significantly faster 99mTc-DTPA transfer rate was found (4.17 +/- 0.83%.min-1 or T1/2R2 = 17.17 +/- 3.38min). Bronchoalveolar lavage (BAL) suggested that the increased permeability measured in Group B could be the result of lung inflammatory responses. Our results have demonstrated the ability of the 99mTc-DTPA clearance test to detect alveolar epithelial damage in horses. Furthermore, we were able to show that a regional analysis of the alveolar-capillary barrier integrity may be performed satisfactorily in the equine patient.

Effect of a set stabled environmental control on pulmonary function and airway reactivity of COPD affected horses.

The aim of this study was to evaluate the respiratory function of horses affected with chronic obstructive pulmonary disease (COPD) when maintained in a barn on wood shavings and fed grass silage for a period of 6 weeks. The mechanics of breathing, blood gas analysis and bronchial reactivity were examined on five horses with COPD at the end of the environment-controlled period (Period B) and the results compared with values obtained after 2 months at pasture (Period A) and after the onset of clinical signs of acute crisis (Period C). The results showed that clinical and functional parameters were similar in healthy horses and in COPD horses placed on pasture or stabled and fed grass silage. Moreover, the bronchial reactivity of COPD horses at pasture was similar to the bronchial reactivity of healthy horses. COPD horses fed grass silage however presented a bronchial reactivity intermediate between those measured after Period A and Period C which suggested they would be more susceptible to develop bronchoconstriction when in contact with inhaled irritants.

Does an acute COPD crisis modify the cardiorespiratory and ventilatory adjustments to exercise in horses?

The present study was conducted to understand better the mechanisms leading to the decrease in exercise capacity observed in horses suffering from chronic obstructive pulmonary disease (COPD). Five COPD horses were submitted to a standardized submaximal treadmill exercise test while they were in clinical remission or in acute crisis. Respiratory airflow, O2 and CO2 fractions in the respired gas, pleural pressure changes and heart rate were recorded, and arterial and mixed venous blood were analyzed for gas tensions, hemoglobin, and plasma lactate concentrations. O2 consumption, CO2 production, expired minute ventilation, tidal volume, alveolar ventilation, cardiac output, total pulmonary resistance, and mechanical work of breathing were calculated. The results showed that, when submaximally exercised, COPD horses in crisis were significantly more hypoxemic and hypercapnic and that their total pulmonary resistance and mechanical work of breathing were significantly higher and their expired minute ventilation significantly lower than when they were in remission. However, their O2 consumption remained unchanged, which was probably due to the occurrence of compensatory mechanisms, i.e., higher heart rate, cardiac output, and hemoglobin concentration. Last, their net anaerobic metabolism seemed to be more important.

Environmental control to maintain stabled COPD horses in clinical remission: effects on pulmonary function.

The objective of this study was to test the hypothesis that stabled COPD horses can be maintained in clinical remission by replacing hay by grass silage and bedding made of wood shavings (Period B) and of wheat straw (Period C) during 6 weeks, respectively. At the end of these different periods, the pulmonary function of the horses was assessed by mechanics of breathing and arterial blood analyses. These results were compared to those measured in clinical remission obtained after 2 months in pasture (Period A). No significant difference was observed between these 3 periods neither to values obtained for healthy horses placed during 6 weeks in a hay environment. For all that, COPD horses placed in contact with hay in the same barn developed within mean +/- s.d. 8+/-3 days clinical signs of heaves and significant alterations of pulmonary function parameters.

Technical validation of a face mask adapted for dry powder inhalation in the equine species.

Development of dry powder inhalation (DPI) for horses requires the use of an adapted face mask. In experiment I, 4 masks (A, B, C and D) were tested and factors influencing the delivery of the dry powder were determined. Mask A was one which is commercially available for metered-dose inhalation. Mask B had the same shape as Mask A but an airtight rubber seal was added for the connection between the mask and horse's head. Mask C was a prototype adapted for DPI with connection for the DPI device between the nostrils, airtight expiratory valves in front of each nostril and airtight rubber seal to attach the mask on the horse's head. Mask D was the same as Mask C but the airtight expiratory valve was situated in front of one nostril and the connection for the DPI device was placed in front of the other nostril. Inhalet emptying and peak inspiratory pressure were measured on 5 healthy horses with each face mask. Both Masks A and B gave a low rate of inhalet emptying. Inspiratory pressures created in Masks C and D were negative enough to ensure inhalet emptying rates of mean +/- s.d. 98.28 +/- 1.79% and 100% respectively. In experiment 2, the face masks giving the greatest inhalet emptying were used to test the therapeutic efficacy of ipratropium bromide DPI. This was tested on 6 horses suffering from acute exacerbation of chronic obstructive pulmonary disease (COPD). At a dose of 200 micrograms/100 kg bwt, ipratropium administered with Mask D improved significantly pulmonary function measurements compared to baseline values and placebo inhalation. With Mask C, a double dose of ipratropium (400 micrograms/100 kg bwt) was necessary to improve these parameters compared to baseline values. This indicated the importance of locating the DPI device in front of one nostril. It was concluded that inhalet emptying is correlated to inspiratory pressures measured in the face masks. Secondly, these pressures are in turn dependent on the air-tightness of the mask, i.e. air-tightness of the expiratory valve and close connection between the horse's head and the mask. Thirdly, position of the DPI device in front of a nostril allows bronchodilation at a dose half that required when the device is placed between the nostrils. Finally DPI using Mask D (EquiPoudre) is a rapid, effective and well tolerated inhalation treatment for COPD horses.

Airborne dust and aeroallergen concentrations in different sources of feed and bedding for horses.

Standardized methods were used to make quantitative and qualitative assessments of respirable dust and aeroallergens in feed and bedding for horses. Concentrations of airborne dust were measured by using a Rion particle counter, and levels of major aeroallergens implicated in chronic obstructive pulmonary disease were measured by using an Andersen sampler. Laboratory conditions allowed comparison of the different sources of forage, supplements, and bedding without external influences such as ventilation, external temperature and horse activity affecting the result. Grass silages of approximately 50% dry matter and alfalfa pellets appeared to be very good sources of forage with low levels of dust and aeroallergens. The studied good quality straw was significantly less dusty with fewer allergens than the wood shavings. Supplements, such as whole grains and molassed concentrates, contained many respirable particles and aeroallergens. Rolled grains were significantly more dusty than good hay.

Airway response of horses with COPD to dry powder inhalation of ipratropium bromide.

To determine the effects of the dry powder inhalation (DPI) of ipratropium bromide (ipratropium) on the airways of health horses and the dose-response curve in horses suffering from chronic obstructive pulmonary disease (COPD) by means of pulmonary function tests, five healthy horses were first studied. Ipratropium (2400 micrograms ipratropium horse-1) was contained in gelatine capsules and administered using a dry powder device connected to an adapted face mask. Pulmonary function tests were recorded before inhalation and 15 and 60 min after inhalation. No modification of pulmonary function was observed. The airway response to ipratropium DPI was then determined in six horses suffering from COPD. To induce airway obstruction, the horses were bedded on straw and fed hay. When the maximal change in pleural pressure during tidal breathing exceeded 1.96 kPa, pulmonary function tests were recorded before DPI, and 15 and 60 min post-inhalation. Placebo (six capsules horse-1) or ipratropium (600, 1200 and 2400 micrograms horse-1) was administered in a randomized order to each horse using the dry powder device and the adapted face mask. Neither ipratropium nor placebo DPI affected respiratory frequency (f) or tidal volume (VT). Inhalation of 600 micrograms ipratropium horse-1 resulted in a delayed decrease of total pulmonary resistance (RL) whereas dynamic compliance (Cdyn) was improved (although not significantly) at both times of measurement when compared with values following placebo inhalation. Simultaneous decreased RL and increased Cdyn, was observed within 15 min after DPI of 1200 micrograms ipratropium horse-1 and persisted for the 1 h duration of the experiment. Doubling the dose also improved pulmonary function but not significantly more than following inhalation of 1200 micrograms ipratropium. No systemic side effects were observed in either group of horses.

Analysis of equine scintigraphical lung images.

A method is proposed (1) to create inhalation to perfusion ratio (I/Q) images from equine lung scintiscans and (2) to analyse these I/Q images. This method was applied to five healthy horses in order to establish reference ranges of I/Q distribution pattern. Computed I/Q images were divided in three regions based on the activity due to the inhalation (I) versus perfusion (Q) procedure. For each region a regional mismatching factor (Iri), i.e. the I/Q of the region, and an intraregional mismatching factor (Lri), which expresses the variability of pixels' I/Q within the region, were calculated. The Per(Ri) and Cen(Ri), which are the percentage of pixels in the parenchymal and in the central parts of the lung belonging to the region, were also computed. Results of this analysis showed a good match between I and Q distribution pattern.

Aerosol therapy in the equine species.

Inhalation therapy plays an increasing role in the management of equine respiratory disorders. This alternative to systematic treatment permits a high concentration of medication to act locally while minimizing side effects and residues. In human medicine, literature in this field is prolific and continuously renewed, whereas in veterinary medicine, applications of aerosol therapy are less extensive. This review considers the principles of action of the different types of devices used for inhalation, i.e., nebulization, metered-dose inhalation and dry powder inhalation, describes the technical and practical requirements for their use in the equine species and considers the advantages and disadvantages of each inhalation device. The pharmacological agents currently administered to horses by inhalation are also discussed. Perspectives of aerosol therapy in the equine species, including aerosols already used in human medicine and their potential applications for horses are described.

Effect of serotonergic blockade on calf pulmonary function after the intravenous administration of 3-methylindole.

This study was designed to investigate whether 3-methylindole (3-Mi), a tryptamine analogue, could cause pulmonary injury in calves other than by cytotoxicity. Injection of 3-Mi resulted in a marked increase of respiratory rate, decrease of tidal volume and increase in minute ventilation. Pulmonary mechanics values were also profoundly affected, lung dynamic compliance being reduced to approximately one-third of its baseline value and total pulmonary resistance being increased two-fold. Arterial oxygen partial pressure was dramatically reduced. Successive challenges with 3-Mi after physiological saline pretreatment resulted in quantitatively identical alterations of pulmonary function values. Conversely, all these ventilatory, mechanical and gas exchange changes were abolished by pretreatment with serotonergic antagonists. It was concluded that intravenous administration of 3-Mi to healthy calves induced immediate and reversible bronchoconstriction which affected both central and peripheral airways. Because the effect was abolished by pretreatment with antiserotonin drugs, it is suggested that 3-Mi acts either directly by stimulating serotonergic receptors or indirectly through the release of serotonin from platelets. Current concepts of the physiopathological cascade underlying the toxicity of 3-Mi should, therefore, be re-evaluated in the light of this pharmacological mechanism.