2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

For several years the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) decided not to produce their own guidelines on the diagnosis and treatment of hypertension but to endorse the guidelines on hypertension issued by the World Health Organization (WHO) and International Society of Hypertension (ISH)1,2 with some adaptation to reflect the situation in Europe. However, in 2003 the decision was taken to publish ESH/ESC specific guidelines3 based on the fact that, because the WHO/ISH Guidelines address countries widely varying in the extent of their health care and availability of economic resource, they contain diagnostic and therapeutic recommendations that may be not totally appropriate for European countries. In Europe care provisions may often allow a more in-depth diagnostic assessment of cardiovascular risk and organ damage of hypertensive individuals as well as a wider choice of antihypertensive treatment.

The 2003 ESH/ESC Guidelines3 were well received by the clinical world and have been the most widely quoted paper in the medical literature in the last two years.4 However, since 2003 considerable additional evidence on important issues related to diagnostic and treatment approaches to hypertension has become available and therefore updating of the previous guidelines has been found advisable.

In preparing the new guidelines the Committee established by the ESH and ESC has agreed to adhere to the principles informing the 2003 Guidelines, namely 1) to try to offer the best available and most balanced recommendation to all health care providers involved in the management of hypertension, 2) to address this aim again by an extensive and critical review of the data accompanied by a series of boxes where specific recommendations are given, as well as by a concise set of practice recommendations to be published soon thereafter as already done in 2003; …

2007 Guidelines for the management of arterial hypertension

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)62110-1.pdf

Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials.

Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. In many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.

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Estrogen receptors and human disease

Placebo

Background
Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005.

Objectives
To assess effects of long-term HT (at least 1 year's duration) on mortality, cardiovascular outcomes, cancer, gallbladder disease, fracture and cognition in perimenopausal and postmenopausal women during and after cessation of treatment.

Search methods
We searched the following databases to September 2016: Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO. We searched the registers of ongoing trials and reference lists provided in previous studies and systematic reviews.

Selection criteria
We included randomised double-blinded studies of HT versus placebo, taken for at least 1 year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via the oral, transdermal, subcutaneous or intranasal route.

Data collection and analysis
Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the quality of the evidence by using GRADE methods.

Main results
We included 22 studies involving 43,637 women. We derived nearly 70% of the data from two well-conducted studies (HERS 1998; WHI 1998). Most participants were postmenopausal American women with at least some degree of comorbidity, and mean participant age in most studies was over 60 years. None of the studies focused on perimenopausal women.

In relatively healthy postmenopausal women (i.e. generally fit, without overt disease), combined continuous HT increased the risk of a coronary event (after 1 year's use: from 2 per 1000 to between 3 and 7 per 1000), venous thromboembolism (after 1 year's use: from 2 per 1000 to between 4 and 11 per 1000), stroke (after 3 years' use: from 6 per 1000 to between 6 and 12 per 1000), breast cancer (after 5.6 years' use: from 19 per 1000 to between 20 and 30 per 1000), gallbladder disease (after 5.6 years' use: from 27 per 1000 to between 38 and 60 per 1000) and death from lung cancer (after 5.6 years' use plus 2.4 years' additional follow-up: from 5 per 1000 to between 6 and 13 per 1000).

Oestrogen-only HT increased the risk of venous thromboembolism (after 1 to 2 years' use: from 2 per 1000 to 2 to 10 per 1000; after 7 years' use: from 16 per 1000 to 16 to 28 per 1000), stroke (after 7 years' use: from 24 per 1000 to between 25 and 40 per 1000) and gallbladder disease (after 7 years' use: from 27 per 1000 to between 38 and 60 per 1000) but reduced the risk of breast cancer (after 7 years' use: from 25 per 1000 to between 15 and 25 per 1000) and clinical fracture (after 7 years' use: from 141 per 1000 to between 92 and 113 per 1000) and did not increase the risk of coronary events at any follow-up time.

Women over 65 years of age who were relatively healthy and taking continuous combined HT showed an increase in the incidence of dementia (after 4 years' use: from 9 per 1000 to 11 to 30 per 1000). Among women with cardiovascular disease, use of combined continuous HT significantly increased the risk of venous thromboembolism (at 1 year's use: from 3 per 1000 to between 3 and 29 per 1000). Women taking HT had a significantly decreased incidence of fracture with long-term use.

Risk of fracture was the only outcome for which strong evidence showed clinical benefit derived from HT (after 5.6 years' use of combined HT: from 111 per 1000 to between 79 and 96 per 1000; after 7.1 years' use of oestrogen-only HT: from 141 per 1000 to between 92 and 113 per 1000). Researchers found no strong evidence that HT has a clinically meaningful impact on the incidence of colorectal cancer.

One trial analysed subgroups of 2839 relatively healthy women 50 to 59 years of age who were taking combined continuous HT and 1637 who were taking oestrogen-only HT versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT: Their absolute risk remained low, at less than 1/500. However, other differences in risk cannot be excluded, as this study was not designed to have the power to detect differences between groups of women within 10 years of menopause.

For most studies, risk of bias was low in most domains. The overall quality of evidence for the main comparisons was moderate. The main limitation in the quality of evidence was that only about 30% of women were 50 to 59 years old at baseline, which is the age at which women are most likely to consider HT for vasomotor symptoms.

Authors' conclusions
Women with intolerable menopausal symptoms may wish to weigh the benefits of symptom relief against the small absolute risk of harm arising from short-term use of low-dose HT, provided they do not have specific contraindications. HT may be unsuitable for some women, including those at increased risk of cardiovascular disease, increased risk of thromboembolic disease (such as those with obesity or a history of venous thrombosis) or increased risk of some types of cancer (such as breast cancer, in women with a uterus). The risk of endometrial cancer among women with a uterus taking oestrogen-only HT is well documented.

HT is not indicated for primary or secondary prevention of cardiovascular disease or dementia, nor for prevention of deterioration of cognitive function in postmenopausal women. Although HT is considered effective for the prevention of postmenopausal osteoporosis, it is generally recommended as an option only for women at significant risk for whom non-oestrogen therapies are unsuitable. Data are insufficient for assessment of the risk of long-term HT use in perimenopausal women and in postmenopausal women younger than 50 years of age.

Long term hormone therapy for perimenopausal and postmenopausal women

Background
Oxytocin and prostaglandin are hormones responsible for uterine contraction during the third stage of labour. Receptors in the uterine muscles are stimulated by exogenous or endogenous oxytocin leading to uterine contractions. Nipple stimulation or breastfeeding are stimuli that can lead to the secretion of oxytocin and consequent uterine contractions. Consequently, uterine contractions can reduce bleeding during the third stage of labour.

Objectives
To investigate the effects of breastfeeding or nipple stimulation on postpartum haemorrhage (PPH) during the third stage of labour.

Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 July 2015) and reference lists of retrieved studies.

Selection criteria
Randomised and quasi-randomised controlled trials comparing breast stimulation, breastfeeding or suckling for PPH in the third stage of labour were selected for this review.

Data collection and analysis
Two review authors independently assessed studies for inclusion in terms of risk of bias and independently extracted data. Disagreements were resolved by a third review author.

Main results
We included four trials (4608 women), but only two studies contributed data to the review's analyses (n = 4472). The studies contributing data were assessed as of high risk of bias overall. One of these studies was cluster-randomised and conducted in a low-income country and the other study was carried out in a high-income country. All four included studies assessed blood loss in the third stage of labour. Birth attendants estimated blood loss in two trials. The third trial assessed the hematocrit level on the second day postpartum to determine the effect of the bleeding. The fourth study measured PPH ≥ 500 mL.

Nipple stimulation versus no treatment

One study (4385 women) compared the effect of suckling versus no treatment. Blood loss was not measured in 114 women (59 in control group and 55 in suckling group). After excluding twin pregnancies, stillbirths and neonatal deaths, the main analyses for this trial were performed on 4227 vaginal deliveries. In terms of maternal death or severe morbidity, one maternal death occurred in the suckling group due to retained placenta (risk ratio (RR) 3.03, 95% confidence interval (CI) 0.12 to 74.26; one study, participants = 4227; very low quality evidence); severe morbidity was not mentioned. Severe PPH (≥ 1000 mL) was not reported in this study.

The incidence of PPH (≥ 500 mL) was similar in the suckling and no treatment groups (RR 0.95, 95% CI 0.77 to 1.16; one study, participants = 4227; moderate quality). There were no group differences between nipple stimulation and no treatment regarding blood loss in the third stage of labour (mean difference (MD) 2.00, 95% CI -7.39 to 11.39; one study, participants = 4227; low quality). The rates of retained placenta were similar (RR 1.01, 95% CI 0.14 to 7.16; one study, participants = 4227; very low quality evidence), as were perinatal deaths (RR 1.06, 95% CI 0.57 to 1.98; one study, participants = 4271; low quality), and maternal readmission to hospital (RR 1.01, 95% CI 0.14 to 7.16; one study, participants = 4227; very low quality). We downgraded the evidence for this comparison for risk of bias concerns in the one included trial (inappropriate analyses for cluster design) and for imprecision (wide CIs crossing the line of no difference and, for some outcomes, few events).

Many maternal secondary outcomes (including side effects) were not reported. Similarly, most neonatal secondary outcomes were not reported.

Nipple stimulation versus oxytocin

Another study compared the effect of nipple stimulation (via a breast pump) with oxytocin. Eighty-seven women were recruited but only 85 women were analysed. Severe PPH ≥ 1000 mL and maternal death or severe morbidity were not reported.

There was no clear effect of nipple stimulation on blood loss (MD 15.00, 95% CI -24.50 to 54.50; one study, participants = 85; low quality evidence), or on postnatal anaemia compared to the oxytocin group (MD -0.40, 95% CI -2.22 to 1.42; one study, participants = 85; low quality evidence). We downgraded evidence for this comparison due to risk of bias concerns in the one included trial (alternate allocation) and for imprecision (wide CIs crossing the line of no difference and small sample size).

Many maternal secondary outcomes (including side effects) were not reported, and none of this review's neonatal secondary outcomes were reported.

Authors' conclusions
None of the included studies reported one of this review's primary outcomes: severe PPH ≥ 1000 mL. Only one study reported on maternal death or severe morbidity. There were limited secondary outcome data for maternal outcomes and very few secondary outcome data for neonatal outcomes.

There was no clear differences between nipple stimulation (suckling) versus no treatment in relation to maternal death, the incidence of PPH (≥ 500 mL), blood loss in the third stage of labour, retained placenta, perinatal deaths or maternal readmission to hospital. Whilst these data are based on a single study with a reasonable sample size, the quality of these data are mostly low or very low.

There is insufficient evidence to evaluate the effect of nipple stimulation for reducing postpartum haemorrhage during the third stage of labour and more evidence from high-quality studies is needed. Further high-quality studies should recruit adequate sample sizes, assess the impact of nipple stimulation compared to uterotonic agents such as syntometrine and oxytocin, and report on important outcomes such as those listed in this review.

/pdf/breastfeeding-or-nipple-stimulation-for-reducing-postpartum-vzjiowrj9b.pdf

Breastfeeding or nipple stimulation for reducing postpartum haemorrhage in the third stage of labour

Background: Approximately 30% of childhood cancer survivors (CCSs) will develop chronic kidney disease (CKD) or hypertension 15 to 20 years after treatment ends. The incidence of CKD and hypertension in the 5-year window after cancer therapy is unknown. Moreover, extent of monitoring of CCS with CKD and associated complications in current practice is underexplored. To inform the development of new and existing care guidelines for CCS, the epidemiology and monitoring of CKD and hypertension in the early period following cancer therapy warrants further investigation. Objective: To describe the design and methods of the KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors study, which aims to evaluate the burden of late kidney and blood pressure outcomes in the first ~10 years after cancer therapy, the extent of appropriate screening and complications monitoring for CKD and hypertension, and whether patient, disease/treatment, or system factors are associated with these outcomes. Design: Two distinct, but related studies; a prospective cohort study and a retrospective cohort study. Setting: Five Ontario pediatric oncology centers. Patients: The prospective study will involve 500 CCS at high risk for these late effects due to cancer therapy, and the retrospective study involves 5,000 CCS ≤ 18 years old treated for cancer between January 2008 and December 2020. Measurements: Chronic kidney disease is defined as Estimated glomerular filtration rate <90 mL/min/1.73 m2 or albumin-to-creatinine ratio ≥ 3mg/mmol. Hypertension is defined by 2017 American Academy of Pediatrics guidelines. Methods: Prospective study: we aim to investigate CKD and hypertension prevalence and the extent to which they persist at 3- and 5-year follow-up in CCS after cancer therapy. We will collect detailed biologic and clinical data, calculate CKD and hypertension prevalence, and progression at 3- and 5-years post-therapy. Retrospective study: we aim to investigate CKD and hypertension monitoring using administrative and health record data. We will also investigate the validity of CKD and hypertension administrative definitions in this population and the incidence of CKD and hypertension in the first ~10 years post-cancer therapy. We will investigate whether patient-, disease/treatment-, or system-specific factors modify these associations in both studies. Limitations: Results from the prospective study may not be generalizable to non-high-risk CCS. The retrospective study is susceptible to surveillance bias. Conclusions: Our team and knowledge translation plan is engaging patient partners, researchers, knowledge users, and policy group representatives. Our work will address international priorities to improve CCS health, provide the evidence of new disease burden and practice gaps to improve CCS guidelines, implement and test revised guidelines, plan trials to reduce CKD and hypertension, and improve long-term CCS health.

Jasmine Lee

Papers

Long term hormone therapy for perimenopausal and postmenopausal women

Breastfeeding or nipple stimulation for reducing postpartum haemorrhage in the third stage of labour

KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors: Description of Clinical Research Protocol of the KINDEST-CCS Study