Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer, hormone receptor positive, HER-2 negative.

Background: Predicting the risk of recurrence and response to chemotherapy in women with early breast cancer is crucial to optimise adjuvant treatment. Despite the common practice of using multigene tests to predict recurrence, existing recommendations are inconsistent. Our aim was to formulate healthcare recommendations for the question "Should multigene tests be used in women who have early invasive breast cancer, hormone receptor-positive, HER2-negative, to guide the use of adjuvant chemotherapy?"

Methods: The European Commission Initiative on Breast Cancer (ECIBC) Guidelines Development Group (GDG), a multidisciplinary guideline panel including experts and three patients, developed recommendations informed by systematic reviews of the evidence.

Development and use of health outcome descriptors: a guideline development case study.

Background: During healthcare guideline development, panel members often have implicit, different definitions of health outcomes that can lead to misunderstandings about how important these outcomes are and how to balance benefits and harms. McMaster GRADE Centre researchers developed 'health outcome descriptors' for standardizing descriptions of health outcomes and overcoming these problems to support the European Commission Initiative on Breast Cancer (ECIBC) Guideline Development Group (GDG). We aimed to determine which aspects of the development, content, and use of health outcome descriptors were valuable to guideline developers.

Ability of observer and self-report measures to capture shared decision-making in clinical practice in the UK: a mixed-methods study.

Objectives: To examine how observer and self-report measures of shared decision-making (SDM) evaluate the decision-making activities that patients and clinicians undertake in routine consultations.

Design: Multi-method study using observational and self-reported measures of SDM and qualitative analysis.

Setting: Breast care and predialysis teams who had already implemented SDM.

A descriptive model of shared decision making derived from routine implementation in clinical practice ('Implement-SDM'): Qualitative study.

Objective: Research is needed to understand how Shared Decision-Making (SDM) is enacted in routine clinical settings. We aimed to 1) describe the process of SDM between clinicians and patients; 2) examine how well the SDM process compares to a prescriptive model of SDM, and 3) propose a descriptive model based on observed SDM in routine practice.

Methods: Patients with chronic kidney disease and early stage breast cancer were recruited consecutively via Cardiff and Vale University Health Board (UK) teams.

"What would you recommend doctor?"-Discourse analysis of a moment of dissonance when sharing decisions in clinical consultations.

Background: Proven benefits of Shared Decision Making (SDM) include improved patient knowledge, involvement and confidence in making decisions. Although widely advocated in policy, SDM is still not widely implemented in practice. A common patient-reported barrier is feeling that "doctor knows best"; thus, patients often defer decisions to the clinician.

Low saliva progesterone concentrations are associated with spontaneous early preterm labour (before 34 weeks of gestation) in women at increased risk of preterm delivery.

Saliva progesterone and oestriol concentrations were determined weekly from 24 weeks of gestation in women at increased risk of preterm delivery. Samples were analysed from 28 women with spontaneous onset of labour and delivery before 37 weeks of gestation, and 64 who delivered at term. Saliva progesterone was lower in the 12 women delivering before 34 weeks than in those delivering later, between 34 and 37 weeks (P = 0.

Antenatal glucocorticoid therapy increases glucose delivery to cerebral circulations during acute hypoxemia in fetal sheep during late gestation.

Objective: To determine the effects of 2 maternal injections with dexamethasone on the calculated oxygen and glucose deliveries to fetal cerebral and peripheral circulations during acute hypoxemia in sheep.

Study Design: Beginning at 124 days, ewes received 2 intramuscular injections of either dexamethasone (2 x 12 mg, n = 10) or saline solution (2 x 2 mL, n = 12) 24 hours apart. Hypoxemia (1 hour) was induced 32 hours after the first injection (H1) and 3 days after the second (H2).

Alterations in saliva steroid hormone levels after oral mifepristone administration in women with pregnancies of greater than 41 weeks' gestation.

The objective of this study is to describe the effects of oral mifepristone administration on saliva levels of estradiol, estriol, progesterone, and cortisol in women with postdates pregnancy. As an adjunct to a randomized controlled trial comparing 200 mg oral mifepristone to placebo for cervical ripening and labor induction in women with pregnancies greater than 41 weeks' gestation, saliva samples were obtained before drug administration and every 6 hours thereafter for 24 hours. Estradiol, estriol, progesterone, and cortisol levels were measured by radioimmunoassay.

Predictors of ovarian reserve in young women with breast cancer.

Ovarian reserve can be diminished following treatment for breast cancer. This study evaluated biochemical and biophysical parameters of ovarian reserve in these patients. Biochemical and biophysical tests of ovarian reserve were performed simultaneously in young (age 22-42 years), regularly menstruating women with breast cancer (n=22) and age-matched controls (n=24).

Antral follicle count, anti-mullerian hormone and inhibin B: predictors of ovarian response in assisted reproductive technology?

Objective: The objective of this study was to evaluate the relationship between anti-mullerian hormone (AMH), inhibin B and antral follicle count (AFC) with ovarian response.

Design: Retrospective study.

Setting: Fertility unit.

Inhibin B and anti-Mullerian hormone: markers of ovarian response in IVF/ICSI patients?

Objective: The objective of this study was to investigate whether follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH) and inhibin B could be useful in predicting the ovarian response to gonadotrophin stimulation in assisted reproduction patients who are considered to be poor responders.

Design: Prospective study.

Setting: Fertility unit.

Pituitary-adrenal responses to acute hypoxemia during and after maternal dexamethasone treatment in sheep.

The effects of maternal dexamethasone treatment on hypothalamic-pituitary-adrenal axis function were determined during basal and hypoxemic conditions in maternal and fetal sheep. Under halothane, ewes and their fetuses were catheterized at 117 d gestation (term = 145 d). Starting at 124 d, the ewes received i.

In-vivo concentrations of inhibins, activin A and follistatin in human early pregnancy.

The aims of this study were to investigate the relationship between inhibins, activin A and follistatin in first trimester fetal fluids, maternal serum, placenta and decidua, and to investigate if these hormones are present in the circulation of the early second trimester human fetus. Amniotic and coelomic fluid, maternal serum, placental villi and decidual tissue were obtained from normal pregnancies at 8-12 weeks. Fetal blood by cardiocentesis and maternal blood were collected at 14-16 weeks gestation.

A novel therapy with testosterone and sildenafil for erectile dysfunction in patients on renal dialysis or after renal transplantation.

Background: We undertook a prospective pilot study in a small cohort of patients with renal replacement therapy to determine the cause of erectile dysfunction (ED) and evaluate the role of testosterone replacement therapy and sildenafil.

Methods: We investigated 12 patients (eight post-transplant and four on haemodialysis) who presented with ED for hypogonadism and cavernosal insufficiency. We assessed sexual performance before and after treatment by a questionnaire method based on the modified International Index of Erectile Function (IIEF) and National Institutes of Health (NIH) rating.

Antenatal glucocorticoids reset the level of baseline and hypoxemia-induced pituitary-adrenal activity in the sheep fetus during late gestation.

This study examined the effects of dexamethasone treatment on basal hypothalamo-pituitary-adrenal (HPA) axis function and HPA responses to subsequent acute hypoxemia in the ovine fetus during late gestation. Between 117 and 120 days (term: approximately 145 days), 12 fetal sheep and their mothers were catheterized under halothane anesthesia. From 124 days, 6 fetuses were continuously infused intravenously with dexamethasone (1.

Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid-gestation fetal sheep.

Unbalanced maternal nutrition affects fetal endocrine and cardiovascular systems, sometimes accompanied by changes in growth, although this is usually in late gestation. We determined the effect of moderate restriction for the first half of gestation of maternal dietary protein, or of total calorific intake on isolated resistance artery function of mid-gestation fetal sheep. Welsh Mountain ewes were nutritionally restricted by 30 % of the recommended nutrient intake (globally restricted) or 30 % of the recommended protein intake (protein-restricted), compared to control ewes fed 100 % of recommended nutrient intake, for ~12 days prior to conception and for the subsequent 70 days of gestation.

Germ cell damage and Leydig cell insufficiency in recipients of nonmyeloablative transplantation for haematological malignancies.

Most bone marrow transplant recipients are infertile due to reversible or irreversible testicular failure. However, little is known about the gonadotoxic potential of the newly introduced nonmyeloablative transplants. We undertook a 24-month longitudinal study in a cohort of 32 recipients of nonmyeloablative transplantation to test whether the combined regimen of fludarabine, melphalan and CAMPATH-1H can induce damage to germ cell (GC) and Leydig cell (LC) compartments.

Effects of low dose dexamethasone treatment on basal cardiovascular and endocrine function in fetal sheep during late gestation.

This study investigated the effects on ovine fetal basal cardiovascular and endocrine functions of fetal intravenous dexamethasone treatment, resulting in circulating concentrations that were one-fifth of the values measured clinically in human infants following maternal antenatal glucocorticoid therapy. Between 117-120 days gestation (dGA; term: ca 145 dGA), 26 Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters and a Transonic flow probe positioned around a femoral artery. At 125 +/- 1 dGA, fetuses were infused with dexamethasone (2.

Circulating levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages.

Background: The aim of this study was to investigate the changes in circulating levels and the clinical use of inhibin A, activin A and follistatin as endocrine markers of early pregnancy loss.

Methods: Blood samples were collected from women presenting with a sporadic missed miscarriage (n = 10), and controls having pregnancy termination at 8-12 weeks (n = 15) and from women with a history of unexplained recurrent miscarriages (n = 12) at 6-12 weeks gestation. All samples were assayed for inhibin A, inhibin B, activin A, follistatin, hCG, estradiol and progesterone.

Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies.

Erectile dysfunction (ED) is a well recognised complication of bone marrow transplantation, which affects quality of life in adult patients. Although the major contributory factors include hypogonadism and psychogenic factors, the best treatment still remains to be established due to the complex aetiopathology of the condition. Here, we report our preliminary results in eight patients treated with testosterone replacement therapy and sildenafil.

Gynaecomastia with hypergonadotrophic hypogonadism and Leydig cell insufficiency in recipients of high-dose chemotherapy or chemo-radiotherapy.

Late side-effects of stem cell transplantation include hypogonadism with infertility and sexual dysfunction, but gynaecomastia is less well recognised. We report five cases of gynaecomastia with features of hypergonadotrophic hypogonadism (primary testicular failure), who received either a TBI/cyclophosphamide conditioned allograft (n = 3) or a BEAM autograft (n = 2). Patients receiving an allograft had gynaecomastia, Leydig cell insufficiency (LCI) diminished libido and erectile dysfunction.

Hypogonadotrophism fails to prevent severe testicular damage induced by total body irradiation in a patient with beta-thalassaemia major and acute lymphoblastic leukaemia.

Radiation and chemotherapeutic drugs for cancer produce prolonged and often irreversible gonadal damage. To determine whether total body irradiation (TBI)-induced gonadal damage can be prevented by suppression of pituitary gonadotrophin levels, we studied a patient with transfusion dependent homozygous beta-thalassaemia and acute lymphoblastic leukaemia (ALL) who underwent one-antigen mismatched related bone marrow transplantation (BMT). Our data showed that despite having hypogonadotrophic hypogonadism (HH) prior to BMT, the patient developed primary testicular failure following the procedure, indicating that hypogonadotrophism failed to offer protection against TBI-induced testicular damage in this patient.

Patterns of Leydig cell insufficiency in adult males following bone marrow transplantation for haematological malignancies.

Gonadal and sexual function are key to quality of life following bone marrow transplantation (BMT), but no large studies have been published on Leydig cell (LC) function in adults. LC insufficiency (LCI) can cause premature andropause with its consequences including sexual morbidity from diminished libido and erectile dysfunction (ED). In addition, LCI can result in generalised fatigue and even osteopenia.

Cardiovascular and hypothalamic-pituitary-adrenal axis development in late gestation fetal sheep and young lambs following modest maternal nutrient restriction in early gestation.

The effect of a 15% reduction in maternal nutrition for the first 70 days of gestation on cardiovascular and hypothalamic-pituitary-adrenal (HPA) axis responses to administration of corticotropin releasing hormone (CRH) + arginine vasopressin (AVP) was studied at 128 +/- 0.7 days gestation in fetal sheep and postnatally, at 85 +/- 4.5 days in young lambs.