Feline Platelets in Health and Disease and an Assessment of a New Anticoagulant to Minimise Pseudothrombocytopenia and Pseudoleukocytosis

Platelets are complex blood cells whose primary function is to participate in haemostasis, aggregating at the site of injury to obstruct blood flow out of the vessel. They are non-nucleated cells, derived by division of multinucleated bone marrow stem cells called megakaryocytes. Production of platelets is increased when the total circulating platelet mass declines, through the action of thrombopoietin and other stimulatory cytokines. Platelets contain a complex cytoskeleton and contractile protein network which enables shape change upon stimulation, active extrusion of the contents of storage granules and clot retraction. Platelets synthesise a number of factors which influence other platelets, the coagulation cascade, leukocytes and blood vessels. These are stored in granules and are extruded upon stimulation along a complex series of channels to reach the exterior. Platelet adhesion and aggregation begins with the binding of proteins to specific glycoprotein receptors in the platelet plasma membrane. Collagen, exposed at the site of damage to blood vessels is an important agonist in vivo, but other agonists are numerous and include substances released from activated platelets themselves, such as adenosine diphosphate (ADP) and serotonin, circulating substances such as adrenalin and vasopressin, products of the coagulation cascade such as thrombin, physical factors such as shear stress and stirring, and many foreign substances. The signal derived from the agonist binding is transferred across the plasma membrane to trigger a series of biochemical events which result in platelet shape change, fibrinogen binding, attachment of platelets in aggregates and secretion of granule contents, which recruit other platelets, and culminates with platelets losing their individual integrity to form a platelet mass. Platelet activity is constrained by the physical nature of the blood vessel wall and substances secreted by platelets and endothelial cells, as well as the rapid inactivation of free agonists. Platelet enumeration is a routine part of a full blood count. Both manual methods, using a haemocytometer, and automated methods are available. Estimations of platelet number can be obtained by counting platelets seen in several microscope fields of the blood smear. Automated methods are more accurate than manual methods because of the larger number of cells counted. However, overlap of feline red cell and platelet size results in inaccuracies when aperture-impedance analysers are used. The presence of platelet aggregates in samples produces inaccuracies by all methods, because individual platelets within aggregates cannot be differentiated. Anticoagulants are designed to inhibit blood coagulation and preserve cell morphology for haematological analysis. EDTA is the most frequently used anticoagulant; however, it causes platelet shape change and swelling and does not completely prevent activation or aggregation. In some individual human blood samples pseudothrombocytopenia and concurrent pseudoleukocytosis is seen when EDTA anticoagulant is used and this has been documented in other species. Other anticoagulants may also produce this effect. Citrate is not routinely used for anticoagulation for haematological analysis because of its dilutional effect. Because of the central role of platelets in haemostasis, changes in platelet number or function can have significant consequences. Immune-mediated thrombocytopenia is a rare disease in the cat in contrast to other species. More commonly, feline thrombocytopenia accompanies other diseases such as neoplasia, gastrointestinal disease and virus infection and may be a component of disseminated intravascular coagulation; however, resultant clinical signs of bleeding are not often seen. A variety of drugs and diseases may affect platelet function including renal disease, liver disease, dysproteinaemias, infectious diseases and disseminated intravascular coagulation. Hereditary platelet function disorders recognised in cats include Chediak-Higashi syndrome and von Willebrand's disease. Platelet neoplasia and thrombocythaemia is rare in cats; however thrombocytosis is not and may reflect physiological release from splenic and non-splenic pools or a reactive component of diseases, resulting in accelerated haematopoiesis, inflammatory diseases, some types of neoplasia or following splenectomy. (Abstract shortened by ProQuest.)

Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM)::a trial-based and model-based cost-effectiveness analysis from a stepped wedge, cluster-randomised trial

Abstract Background The AFFIRM intervention aimed to reduce stillbirth and neonatal deaths by increasing awareness of reduced fetal movements (RFM) and implementing a care pathway when women present with RFM. Although there is uncertainty regarding the clinical effectiveness of the intervention, the aim of this analysis was to evaluate the cost-effectiveness. Methods A stepped-wedge, cluster-randomised trial was conducted in thirty-three hospitals in the United Kingdom (UK) and Ireland. All women giving birth at the study sites during the analysis period were included in the study. The costs associated with implementing the intervention were estimated from audits of RFM attendances and electronic healthcare records. Trial data were used to estimate a cost per stillbirth prevented was for AFFIRM versus standard care. A decision analytic model was used to estimate the costs and number of perinatal deaths (stillbirths + early neonatal deaths) prevented if AFFIRM were rolled out across Great Britain for one year. Key assumptions were explored in sensitivity analyses. Results Direct costs to implement AFFIRM were an estimated £95,126 per 1,000 births. Compared to standard care, the cost per stillbirth prevented was estimated to be between £86,478 and being dominated (higher costs, no benefit). The estimated healthcare budget impact of implementing AFFIRM across Great Britain was a cost increase of £61,851,400/year. Conclusions Perinatal deaths are relatively rare events in the UK which can increase uncertainty in economic evaluations. This evaluation estimated a plausible range of costs to prevent baby deaths which can inform policy decisions in maternity services. Trial registration The trial was registered with www.ClinicalTrials.gov, number NCT01777022. </jats:sec

Options in Pregnancy to Increase ActiveLy Sitting (OPALS) Feasibility Study

Background. A negative association between obesity and pregnancy outcomes has been described, as well as between time sedentary and pregnancy outcomes. Most interventions based on physical activity involving obese pregnant women have failed in improving pregnancy outcomes. Exchanging time spent in sedentary activities with time spent in light-intensity activities, performed in a home-based setting, might help morbidly obese pregnant women. We aimed to assess the feasibility of an exercise intervention. Methods. An exercise intervention for morbidly obese pregnant women was designed involving morbidly obese pregnant women. Pregnant women with BMI ≥ 40 kg/m² with 20 or less weeks of gestation were invited to take part in the OPALS Feasibility Study. A home-based approach was employed. Participants were asked to perform the intervention for at least 12 weeks, and to register their performance in an activity diary. After the intervention, participants were asked to return the activity diary and answer a feasibility questionnaire. Results. In the intervention, 28 participants took part. Six women completed the intervention for 12 weeks or more. All declared they intended to keep on doing the intervention. All women reported that the exercises made them feel better. Conclusion. Empowering, and involving morbidly obese pregnant women in taking care of themselves and giving them realistic tasks to do on their own and around their environment helps to increase commitment, as does avoiding the effect of their own weight whilst exercising. A 20% of compliance was observed in this study, which might be explained by the difficulties that pregnancy and excess weight mean. Thus, for future studies, we suggest adding a supervision plan to increase that number

Reading problems of the bottom third: grades one through six

Thesis (Ed.M.)--Boston Universit

Risk Factors for End Stage Renal Disease in Non-WT1-Syndromic Wilms Tumor

PURPOSE: We assessed risk factors for end stage renal disease in patients with Wilms tumor without known WT1 related syndromes. We hypothesized that patients with characteristics suggestive of a WT1 etiology (early onset, stromal predominant histology, intralobar nephrogenic rests) would have a higher risk of end stage renal disease due to chronic renal failure. We predicted a high risk of end stage renal disease due to progressive bilateral Wilms tumor in patients with metachronous bilateral disease. MATERIALS AND METHODS: End stage renal disease was ascertained in 100 of 7,950 nonsyndromic patients enrolled in a National Wilms Tumor Study during 1969 to 2002. Risk factors were evaluated with cumulative incidence curves and proportional hazard regressions. RESULTS: The cumulative incidence of end stage renal disease due to chronic renal failure 20 years after Wilms tumor diagnosis was 0.7%. For end stage renal disease due to progressive bilateral Wilms tumor the incidence was 4.0% at 3 years after diagnosis in patients with synchronous bilateral Wilms tumor and 19.3% in those with metachronous bilateral Wilms tumor. For end stage renal disease due to chronic renal failure stromal predominant histology had a HR of 6.4 relative to mixed (95% CI 3.4, 11.9; p<0.001), intralobar rests had a HR of 5.9 relative to no rests (95% CI 2.0, 17.3; p=0.001), and Wilms tumor diagnosis at less than 24 months had a HR of 1.7 relative to 24 to 48 months and 2.8 relative to greater than 48 months (p=0.003 for trend). CONCLUSIONS: Metachronous bilateral Wilms tumor is associated with high rates of end stage renal disease due to surgery for progressive Wilms tumor. Characteristics associated with a WT1 etiology markedly increased the risk of end stage renal disease due to chronic renal failure despite the low risk in non-WT1 syndromic cases overall

C-STICH2: emergency cervical cerclage to prevent miscarriage and preterm birth—study protocol for a randomised controlled trial

Abstract Background Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach. Methods C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis. Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0–27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy. Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children’s Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat. Discussion To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies. Trial registration ISRCTN Registry ISRCTN12981869 . Registered on 13th June 2018

Portfolio Vol. I N 2

Wiley, Thomas R. In the Cathedral, Mexico City . Picture. 2. Whitehead, Richard Jr. Izzy was a Lady, After All . Prose. 3. Beckham, Adela. Rain on a March morning . Poem. 6. Beckham, Adela. Heaven . Poem. 6. Deane, Dorothy. Temptation . Poem. 6. Kellogg, Elizabeth. Gruess Dich Gott . Prose. 7. Nadel, Norman. The Duchess . Poem. 8. Dick, Pewilla. The Sligo Fisherman . Prose. 9. Deane, Dorothy. Against the Winter . Poem 12. Flory, Doris Jean. A problem . Poem 12. Travis, Paul Bough. My First View of the Congo Forest . Picture. 13. Bellows, George. Stag at Sharkey\u27s . Picture. 13. B.C.W. Aspiration . Poem. 14. Stewart, John. On Record . Prose 14. Sweitzer, Harry J. Playing Around . Prose. 15. Ellsberg, Edward. Book Parade: Hell on Ice . Prose. 15. B.C.W. End of Winter . Poem. 16. Wiley, Thomas R. End of Winter . Picture. 16. Deeter, Robert. Television, How, Where, and When . Prose. 17. Brush, Jane. Love A La Mode . Poem. 20. Brush, Jane. Radio! . Poem. 20. Brush, Jane. Backward Glance . Poem. 20. Brush, Jane. Homo Paradoxus . Poem. 20. Brush, Jane. The Sardonic Slant . Poem. 20. Brush, Jane. Baths . Prose. 20. Wilson, Gordon. Brushword . Cartoon. 20

Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial

Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. The EME Programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office in Scotland and National Institute for Social Care and Research in Wales