https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000597

2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

BACKGROUND Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone. METHODS We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone. RESULTS A total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%. CONCLUSIONS Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.)

/pdf/chemohormonal-therapy-in-metastatic-hormone-sensitive-avs80yzvd3.pdf

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer

Degradation of the mammalian cyclin-dependent kinase (CDK) inhibitor p27 is required for the cellular transition from quiescence to the proliferative state. The ubiquitination and subsequent degradation of p27 depend on its phosphorylation by cyclin-CDK complexes. However, the ubiquitin-protein ligase necessary for p27 ubiquitination has not been identified. Here we show that the F-box protein SKP2 specifically recognizes p27 in a phosphorylation-dependent manner that is characteristic of an F-box-protein-substrate interaction. Furthermore, both in vivo and in vitro, SKP2 is a rate-limiting component of the machinery that ubiquitinates and degrades phosphorylated p27. Thus, p27 degradation is subject to dual control by the accumulation of both SKP2 and cyclins following mitogenic stimulation.

SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.

Theory provides a helpful basis for designing interventions to change behaviour but offers little guidance on how to do this. This paper aims to illustrate methods for developing an extensive list of behaviour change techniques (with definitions) and for linking techniques to theoretical constructs. A list of techniques and definitions was generated from techniques published in two systematic reviews, supplemented by “brainstorming” and a systematic search of nine textbooks used in training applied psychologists. Inter-rater reliability of extracting the techniques and definitions from the textbooks was assessed. Four experts judged which techniques would be effective in changing 11 theoretical constructs associated with behaviour change. 
Thirty-five techniques identified in the reviews were extended to 53 by brainstorming and to 137 by consulting textbooks. Agreement for the 53 definitions was 74.7 per cent (15.4% cells completed and 59.3% cells empty for both raters). Agreement about the link between the 35 techniques and theoretical constructs was 71.7 per cent of 385 judgments (12.2% agreement that effective and 59.5% agreement that not effective). This preliminary work demonstrates the possibility of developing a comprehensive, reliable taxonomy of techniques linked to theory. Further refinement is needed to eliminate redundancies, resolve uncertainties, and complete technique definitions.

From Theory to Intervention: Mapping Theoretically Derived Behavioural Determinants to Behaviour Change Techniques

In the 2000s, governments in the UK, particularly in England, developed a system of governance of public services that combined targets with an element of terror This has obvious parallels with the Soviet regime, which was initially successful but then collapsed Assumptions underlying governance by targets represent synecdoche (taking a part to stand for a whole); and that problems of measurement and gaming do not matter We examine the robustness of the regime of targets and terror to these assumptions using evidence from the English public health service on reported successes, problems of measurement, and gaming Given this account, we consider the adequacy of current audit arrangements and ways of developing governance by targets in order to counter the problems we have identified

What's measured is what matters: targets and gaming in the English public health care system

Complications from pregnancy and childbirth are the leading cause of death in young women aged 15 to 19 in developing countries, warned a report published last week. An estimated 70 000 adolescent mothers die each year because they have children before they are physically ready for parenthood, the report says.

 ![][1] 

The fifth annual State of the World's Mothers report, published by the international charity Save the Children, found that 13 million births (a tenth of all births worldwide) each year are to women aged under 20, and more than 90% of these births are in …

 [1]: /embed/graphic-1.gif

/pdf/pregnancy-and-childbirth-are-leading-causes-of-death-in-1e84ui0w8v.pdf

Pregnancy and childbirth are leading causes of death in teenage girls in developing countries

A large advertising campaign to encourage families, and particularly children, to eat more healthily and be more active was launched last week by the English government as part of a three year programme that aims to achieve a “lifestyle revolution” to halt the growing epidemic of obesity.

The Change4Life programme will include education, individualised support, and activities to encourage people to understand the impact of obesity on their health and to make changes to achieve and maintain a healthy body weight. Its central message is that 90% of today’s children will be overweight or obese and at risk from serious diseases by 2050 without intervention.

Launching the initiative, Dawn Primarolo, the public health …

English government launches initiative to cut obesity.

Nearly 700 000 people signed up in the first 24 hours of the launch of an app to help track the spread of coronavirus across the UK in real time and collect information on the range of self-reported symptoms and the characteristics of those most at risk.

The Covid Symptom Tracker app (covid.joinzoe.com) enables users to make a daily report of any symptoms. It is available free of charge to members of the public in the UK. The app has also been given to 5000 twins and their families recruited from the ongoing TwinsUK cohort study.1

“The aim of the app is to help slow the outbreak” by understanding what measures work, said the researchers from King’s College London and Guy’s and St Thomas’ Hospitals in partnership with ZOE, a spin-off health data science company from King’s. “It will …

https://www.bmj.com/content/bmj/368/bmj.m1263.full.pdf

Covid-19: Researchers launch app to track spread of symptoms in the UK.

More than a fifth of babies in England are delivered by caesarean section, latest hospital statistics for 2000-1 show. The rate increased from 18% in 1997-8 to 22% in 2000-01

Over half of the total of 560 000 hospital deliveries in the analysis were spontaneous, both in onset and delivery. However, 21% of deliveries were induced, and 14% of women had an episiotomy. Just over 11% of deliveries were instrumental, with …

Caesarean section rate in England reaches 22

Doctors in the United Kingdom have been alerted to the symptoms of ricin poisoning after a small amount was found last week when police raided a flat in north London.

The Department of Health alerted the health service on the symptoms of ricin poisoning after police found castor oil beans, from which ricin is extracted, and equipment for crushing the beans at the raided flat. Scientists at the Defence Science and Technology Laboratories at Porton Down in Wiltshire identified a small quantity of material found in the flat as ricin.

In a statement sent immediately …

Susan Mayor

Papers

Pregnancy and childbirth are leading causes of death in teenage girls in developing countries

English government launches initiative to cut obesity.

Covid-19: Researchers launch app to track spread of symptoms in the UK.

Caesarean section rate in England reaches 22

UK doctors warned after ricin poison found in police raid