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•This international Delphi panel of 12 multidisciplinary experts explored 7 topics related to SCD management during pregnancy.•Based on consensus reached in several areas, recommendations were formulated to inform clinical care for pregnant patients with SCD.

We performed a meta-analysis to evaluate the risk of venous thromboembolism (VTE) in pregnant women with essential thrombocythemia. Twenty-one trials and 756 pregnancies met inclusion criteria. The absolute VTE risk in the antepartum period is not above a threshold where low-molecular-weight heparin (LMWH) prophylaxis is clearly indicated or below a threshold where LMWH should be withheld (2.5%; 95% CI, 1.3-4.3). Postpartum, the absolute VTE risk is above a threshold where postpartum LMWH prophylaxis should be considered (4.4%; 95% CI, 1.2-9.5).

We performed a meta-analysis to evaluate the risk of venous thromboembolism (VTE) in pregnant women with essential thrombocythemia. Twenty-one trials and 756 pregnancies met inclusion criteria. The absolute VTE risk in the antepartum period is not above a threshold where low-molecular-weight heparin (LMWH) prophylaxis is clearly indicated or below a threshold where LMWH should be withheld (2.5%; 95% CI, 1.3-4.3). Postpartum, the absolute VTE risk is above a threshold where postpartum LMWH prophylaxis should be considered (4.4%; 95% CI, 1.2-9.5).

The incidence of haematological malignancies in pregnancy ranges from 1 in 1000 to 1 in 10,000. International prospective epidemiology, management and outcome data are important to gain further knowledge of haematological malignancies in pregnancy. The management of haematological malignancies in pregnancy is complex and requires a multidisciplinary approach. The clinician and mother need to address both maternal and fetal well-being. The mother should be provided with the necessary information and support to make informed decisions regarding the pregnancy and disease management. The haematological malignancies are a diverse group with varied presenting features, pathophysiology, treatment options, levels of urgency to commence treatment in pregnancy, effect on maternal and fetal outcome and overall prognosis. We have reviewed the published research in this area, and provide concise up-to-date guidance on the management of haematological malignancies in pregnancy.

Maternal smoking is a risk factor associated with nicotine abuse, so the effect of perinatal nicotine exposure was studied on the responsiveness to nicotine across adolescence in the rat. Pregnant Sprague-Dawley rats were implanted with s.c. Alzet osmotic minipumps delivering nicotine (l-nicotine hydrogen tartrate, 2 mg/kg/day free base) or vehicle (0.9% saline) on gestational day 7. There was no effect of nicotine on dam weight gain, food consumption, or water consumption or on the number of live pups or weights at the time of birth. Pups were cross-fostered to obtain the following prenatal/postnatal exposure groups: control/control, nicotine/nicotine, nicotine/control, and control/nicotine. On postnatal days 28, 35, 49, and 63, nicotine-stimulated (86)Rb(+) efflux was measured in synaptosomes prepared from the frontal cortex, hippocampus, striatum (STR), and thalamus (THL), using a previously developed method. Significant effects of treatment and concentration were detected in all four brain regions, and significant effects of age were observed in the STR and THL. Significant interactions of age and treatment were observed in each of the four brain regions. Nicotine-stimulated (86)Rb(+) efflux peaked during adolescence in control rats. However, perinatal exposure to nicotine eliminated this peak during adolescence. These results are consistent with recent behavioral and receptor binding results from other laboratories and are the first direct evidence at the cellular level that the nicotinic acetylcholine receptor response varies during adolescence and is affected by perinatal nicotine exposure.

The aim of the present studies was to further delineate the role of striatal and limbic dopaminergic versus limbic noradrenergic blockade in the pharmacologic and perhaps therapeutic action of antipsychotic drugs. Metoclopramide shares many properties of antipsychotic neuroleptic drugs, including the production of extrapyramidal side effects, but is not an efficacious antipsychotic agent. This drug was a potent blocker of dopamine (DA) receptors in both striatum and limbic forebrain (comparable in potency to that of chlorpromazine) as evidenced from the increase in homovanillic acid in both brain structures. In contrast, metoclopramide was a weak inhibitor of the norepinephrine (NE) receptor-coupled adenylate cyclase system in the limbic forebrain. Molindone, which is reported not to block DA-sensitive adenylate cyclase, was a potent in vivo blocker of DA receptors in both striatum and limbic forebrain and also inhibited markedly the cyclic AMP response to NE in the limbic forebrain. The phenothiazine derivative, thiethylperazine, was also a potent blocker of DA receptors in both brain areas and displayed an IC50 for NE blockade in the limbic forebrain comparable to that of chlorpromazine. The present results support the view that the ability and potency of drugs to block DA receptors parallels their ability and potency to cause extrapyramidal symptoms in man. Moreover, these results suggest that the blockade of NE receptor-coupled adenylate cyclase systems in brain may be relevant to both the pharmacologic and therapeutic activity of antipsychotic drugs.

Recruitment and retention of direct service workers can be a major problem for administrators of community mental health organizations. This paper, based on a nationwide study of psychosocial rehabilitation workers and administrators, examines the congruity of worker and administrator perceptions of worker motivation for entering and leaving the field. Workers are motivated by the intrinsic nature of the work to enter into and stay in the field. Job burnout is as important as low pay in forcing workers out of the field. Administrators, however, perceive money to be a major factor motivating workers to enter the field and perceive external opportunities as forces that pull them away. Thus, administrators must address their workers' needs if their agencies are to offer quality services.

The present studies were undertaken to assess the structural and steric requirements for ß-phenethylamines as agonists of the noradrenergic cyclic AMP generating system in slices of the rat limbic forebrain. Significant agonist activity of ß-phenethylamines requires a ß-3,4-dihydroxyphenethylamine with a ß-hydroxyl group in the R configuration. Thus, dopamine did not stimulate the system at concentrations up to 10-3 M. Moreover, ß-hydroxyphenethylamines without a 3,4-catechol group (octopamine, phenylephrine, p-hydroxynorephedrine, metaraminol and methoxamine)-though exerting a-agonist activity in peripheral tissues-lack agonist activity in this particular cyclic AMP generating system. The effects of (R)-norepinephrine and (R)-isoproterenol at maximal concentrations were not additive. The results lend further support to the view that the cyclic AMP generating system in slices of the limbic forebrain is part of a norepinephrine receptor coupled adenylate cyclase system with a subpopulation of receptors that are ß in nature.

The Philadelphia-negative myeloproliferative disorders, polycythaemia vera, essential thrombocythaemia and myelofibrosis are uncommon clonal haematological malignancies that are generally diagnosed from late middle age onwards. Each of these disorders has unique features but their clinical courses have similarities, including thrombosis, haemorrhage, a tendency for progressive myelofibrosis and, the development of acute myeloid leukaemia. Myelofibrosis is associated with a much poorer prognosis than the other conditions and death, usually due to progressive bone marrow failure or leukaemia. Recently, a mutation at position 617 in exon 14 of the JAK2 gene (JAK2 V617F) has been identified in the majority of patients with polycythaemia vera and half of those with essential thrombocythaemia or myelofibrosis. This has improved diagnostic pathways, but challenges the current classification. Current treatment for these patients involves aggressive management of thrombotic risk factors, aspirin for most patients except where contraindicated and cytoreductive agents such as hydroxycarbamide (hydroxyurea) for patients at high risk of thrombosis.

Multiple factors are likely to contribute to the pathogenesis of thrombosis in Essential thrombocythaemia (ET) including platelet number, activation of platelets and leukocytes; the formation of platelet leucocyte aggregates, and circulating prothrombotic and endothelial factors. The normal functional activity of platelets depends on the presence of platelet glycoprotein complexes, which play an important role in platelet adhesion and aggregation. A number of polymorphisms in platelet glycoproteins have been correlated with thrombotic events in hematologically normal patients. Particular polymorphisms of interest include three within the glycoprotein Ibα gene: −5T/C (affecting a Kozak sequence), 1018C/T (T145M, encoding Human Platelet Antigen − 2), a variable number of tandem repeats (VNTR) in a region encoding the macroglycopeptide and one polymorphism C807T, within the glycoprotein Ia gene. To date whether there is a relationship between these platelet glycoprotein polymorphisms and the clinical features of ET has not been determined. In this study samples obtained from 797 ET patients recruited to the 3 large prospective PT–1 trials were genotyped for the polymorphisms of interest and the results were correlated with clinical events including haemorrhagic and arterial or venous thrombotic events in the year prior to diagnosis and following trial entry (median 30 months). The VNTR data were analysed using the sum of the number of repeats of both alleles and treated as a continuous variable using logistic regression for retrospective and a Cox survival model for prospective analyses; other polymorphisms were analysed using the Chi-squared test for the retrospective clinical events, and log-rank survival analysis for the prospective clinical events. Neither the C807T, −5T/C Kozak nor the T145M polymorphism was associated with clinical events in the ET patient cohort. Interestingly the number of VNTR repeats was inversely associated with (p=0.02) rate of arterial events after trial entry in this patient cohort, but not for events in the year prior to diagnosis or post trial entry venous thrombotic or haemorrhagic events. This analysis suggested that a decreasing sum of VNTR were associated with an increased risk of arterial thrombosis, the degree of increase in risk was 75% per repeat (95% confidence interval 1.0–2.9). After multivariate analysis of this data with correction for age, sex, JAK2V617F and MPLW515L/K status the effect of the number of VNTR repeats remained significant (p=0.048). These results suggest that the C807T, T145M and −5T/C Kozak polymorphisms do not correlate with clinical events in ET. However a reduction in the number of VNTR within the glycoprotein Ibα gene was progressively associated with arterial events post trial entry (p=0.024) and remained significant on multivariate analysis (p=0.048).

Multiple factors are likely to contribute to the pathogenesis of thrombosis in Essential thrombocythaemia (ET) including platelet number, activation of platelets and leukocytes; the formation of platelet leucocyte aggregates, and circulating prothrombotic and endothelial factors. The normal functional activity of platelets depends on the presence of platelet glycoprotein complexes, which play an important role in platelet adhesion and aggregation. A number of polymorphisms in platelet glycoproteins have been correlated with thrombotic events in hematologically normal patients. Particular polymorphisms of interest include three within the glycoprotein Ibα gene: −5T/C (affecting a Kozak sequence), 1018C/T (T145M, encoding Human Platelet Antigen − 2), a variable number of tandem repeats (VNTR) in a region encoding the macroglycopeptide and one polymorphism C807T, within the glycoprotein Ia gene. To date whether there is a relationship between these platelet glycoprotein polymorphisms and the clinical features of ET has not been determined. In this study samples obtained from 797 ET patients recruited to the 3 large prospective PT–1 trials were genotyped for the polymorphisms of interest and the results were correlated with clinical events including haemorrhagic and arterial or venous thrombotic events in the year prior to diagnosis and following trial entry (median 30 months). The VNTR data were analysed using the sum of the number of repeats of both alleles and treated as a continuous variable using logistic regression for retrospective and a Cox survival model for prospective analyses; other polymorphisms were analysed using the Chi-squared test for the retrospective clinical events, and log-rank survival analysis for the prospective clinical events. Neither the C807T, −5T/C Kozak nor the T145M polymorphism was associated with clinical events in the ET patient cohort. Interestingly the number of VNTR repeats was inversely associated with (p=0.02) rate of arterial events after trial entry in this patient cohort, but not for events in the year prior to diagnosis or post trial entry venous thrombotic or haemorrhagic events. This analysis suggested that a decreasing sum of VNTR were associated with an increased risk of arterial thrombosis, the degree of increase in risk was 75% per repeat (95% confidence interval 1.0–2.9). After multivariate analysis of this data with correction for age, sex, JAK2V617Fand MPLW515L/Kstatus the effect of the number of VNTR repeats remained significant (p=0.048). These results suggest that the C807T, T145M and −5T/C Kozak polymorphisms do not correlate with clinical events in ET. However a reduction in the number of VNTR within the glycoprotein Ibα gene was progressively associated with arterial events post trial entry (p=0.024) and remained significant on multivariate analysis (p=0.048).