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It is vital that flood risks from multiple sources to the national Strategic Road Network are well understood, to help minimise disruption, reduce risk to people and to help prioritise maintenance programmes. Highways England have undertaken research to update their current understanding of risk based on improved flood mapping, plus data collected on flooding ‘hot spots’ through a concerted programme to record flooding events, severity and causes over the last 5 years. Building on the previous risk assessment, the roads layer was interrogated against new flood hazard data for multiple sources of flooding. The road network was divided into 100m segments in order to capture a strong spatial understanding of predicted flood risk from each source, but also summarised on a 1km scale and a management area level to aid prioritisation at varying scales. The 1 km grids were then ranked across England according to each source of flooding, and also an overall rank was derived through summing these ranks together. This was validated against detailed spatial ‘hot spot’ database recorded by Highways England, based on over 12,300 records, collected over 5 years.

Background: Older patients with advanced cancer who are 100% certain they will be cured pose unique challenges for clinical decision making, but to the authors' knowledge, the prevalence and correlates of absolute certainty about curability (ACC) are unknown., Methods: Cross-sectional data were collected in a geriatric assessment trial. ACC was assessed by asking patients, "What do you believe are the chances that your cancer will go away and never come back with treatment?" Response options were 100% (coded as ACC), >50%, 50/50, <50%, 0%, and uncertain. The willingness to bear adversity in exchange for longevity was assessed by asking patients to consider trade-offs between survival and 2 clinical outcomes that varied in abstractness: 1) maintaining quality of life (QOL; an abstract outcome); and 2) specific treatment-related toxicities (eg, nausea/vomiting, worsening memory). Logistic regression was used to assess the independent associations between willingness to bear adversity and ACC., Results: Of the 524 patients aged 70 to 96 years, approximately 5.3% reported that there was a 100% chance that their cancer would be cured (ACC). ACC was not found to be significantly associated with willingness to bear treatment-related toxicities, but was more common among patients who were willing to trade QOL for survival (adjusted odds ratio, 4.08; 95% CI, 1.17-14.26)., Conclusions: Patients who were more willing to bear adversity in the form of an abstract state, namely decreased QOL, were more likely to demonstrate ACC. Although conversations regarding prognosis should be conducted with all patients, those who are willing to trade QOL for survival may especially benefit from conversations that focus on values and emotions., (© 2019 American Cancer Society.)

Cancer and neurocognitive disorders, such as dementia and delirium, are common and serious diseases in the elderly that are accompanied by high degree of morbidity and mortality. Furthermore, evidence supports the under-diagnosis of both dementia and delirium in older adults. Complex questions exist regarding the interaction of dementia and delirium with cancer, beginning with guidelines on how best measure disease severity, the optimal screening test for either disorder, the appropriate level of intervention in the setting of abnormal findings, and strategies aimed at preventing the development or progression of either process. Ethical concerns emerge in the research setting, pertaining to the detection of cognitive dysfunction in participants, validity of consent, disclosure of abnormal results if screening is pursued, and recommended level of intervention by investigators. Furthermore, understanding the ways in which comorbid cognitive dysfunction and cancer impact both cancer and non-cancer-related outcomes is essential in guiding treatment decisions. In the following article, we will discuss what is presently known of the interactions of pre-existing cognitive impairment and delirium with cancer. We will also discuss identified deficits in our knowledge base, and propose ways in which innovative research may address these gaps., (Copyright © 2016. Published by Elsevier Ltd.)

Chemotherapy-related cognitive impairment (CRCI) can occur during or after chemotherapy and represents a concern for many patients with cancer. Among older patients with cancer, in whom there is little clinical trial evidence examining side effects like CRCI, many unanswered questions remain regarding risk for and resulting adverse outcomes from CRCI. Given the rising incidence of cancer with age, CRCI is of particular concern for older patients with cancer who receive treatment. Therefore, research related to CRCI in older patients with cancers is a high priority. In this manuscript, we discuss current gaps in research highlighting the lack of clinical studies of CRCI in older adults, the complex mechanisms of CRCI, and the challenges in measuring cognitive impairment in older patients with cancer. Although we focus on CRCI, we also discuss cognitive impairment related to cancer itself and other treatment modalities. We highlight several research priorities to improve the study of CRCI in older patients with cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To determine the effects of tibolone or oestradiol (E(2) )/norethisterone acetate (NETA) hormone replacement therapy on glucose and insulin metabolism in postmenopausal women., Design: Single-centre double-blind placebo-controlled randomized clinical trial., Subjects/methods: We randomized 105 healthy postmenopausal women to tibolone 2·5 mg daily, continuous combined oral E(2) 2 mg/NETA 1 mg daily or placebo over a 2-year study. We performed intravenous glucose tolerance tests (IVGTT) with measurements of plasma glucose, insulin and C-peptide concentrations and the IVGTT glucose elimination rate, k. Mathematical modelling was performed to determine measures of insulin sensitivity, S(i) , pancreatic insulin secretion and hepatic and plasma insulin elimination., Results: Tibolone decreased S(i) to 53-63% and k to 72-79% of baseline values but increased IVGTT phase 2 C-peptide concentrations 1·6-1·8-fold and pancreatic insulin secretion 2·2-2·4-fold, so overall IVGTT glucose concentrations were unaffected. Similar, but for k, significantly smaller changes in insulin and C-peptide secretion were seen with E(2) /NETA, also with no effect on overall IVGTT glucose concentrations., Conclusions: Tibolone reduces insulin sensitivity. Healthy postmenopausal women seem able to compensate for this and maintain normal postload glucose concentrations, but it may not be advisable to prescribe tibolone to women with, or at increased risk for, diabetes., (© 2012 Blackwell Publishing Ltd.)

Objective: Menopause diminishes insulin secretion and elimination, increases risk of diabetes and adversely affects lipoprotein metabolism. This study was undertaken to establish whether oral oestradiol plus dydrogesterone postmenopausal hormone therapy can modify these changes., Design: Randomized prospective trial of postmenopausal women taking low dose therapy (1 mg/day oestradiol-17 beta with 5 or 10 mg/day dydrogesterone for days 17-28 of each cycle, n = 15) or high dose therapy (2 mg/day oestradiol-17 beta with 10 or 20 mg/day orally administered dydrogesterone, n = 9)., Measurements: Patients underwent measurement of glucose, insulin and C-peptide in the fasting state and during an intravenous glucose tolerance test (IVGTT) at baseline and after 12 and 24 cycles of treatment. Modelling analysis was used to derive measures of insulin secretion, elimination and sensitivity. Fasting serum lipids, lipoproteins and apolipoproteins were also measured., Results: In both groups there were significant reductions in fasting glucose, insulin and C-peptide. Pancreatic insulin secretion during the IVGTT was increased by treatment (ranging from 45% to 92%, P < 0.01). Insulin elimination was increased at both the peripheral (16% to 43%, P < 0.05) and hepatic (18% to 31%, P < 0.05) levels. Insulin sensitivity was unaffected. Low density lipoprotein (LDL) cholesterol was reduced and high density lipoprotein (HDL) cholesterol increased with treatment., Conclusions: Postmenopausal hormone therapy with oestradiol plus dydrogesterone can favourably affect lipoprotein concentrations and can reverse menopause-associated changes in insulin secretion and elimination.

Whether hormone replacement therapy (HRT) is beneficial for coronary heart disease (CHD) is controversial. We hypothesized that continuous combined transdermal HRT may have benefits on CHD risk markers without the potential adverse effects seen with certain other HRT regimens. Sixty apparently healthy postmenopausal women, aged 40-65 years, entered a prospective, double-blind, randomized, placebo-controlled clinical trial; 55 women completed the 6-month study. Women received either transdermal oestradiol 17beta 0.05 mg and norethisterone acetate 0.125 mg daily, or identical placebo. Circulating markers of vascular function and remodelling, forearm blood flow, lipids and lipoproteins, glucose and insulin, and haemostatic safety parameters were measured at baseline and after treatment. Compared with placebo after 6 months, HRT administration resulted in decreased E-selectin (P < 0.01), and angiotensin-converting-enzyme (ACE; P = 0.05). Cholesterol (P < 0.05), low-density lipoproteins (LDL; P < 0.05), high-density lipoprotein3 (HDL3; P < 0.05) and apolipoproteins AII (P < 0.05) and B (P < 0.05), and fasting insulin (P < 0.05) also decreased in the HRT group. Factor VII coagulation activity decreased (P < 0.01) and plasminogen activator inhibitor-1 and fibrin D-dimer increased (P < 0.05) in the HRT group, whilst prothrombin fragment 1 + 2 (P < 0.05) decreased, more so in the placebo group. There were no changes in matrix metalloproteinase (MMP)-2, or in LDL particle size. This transdermal HRT had beneficial effects on vascular function and CHD risk markers.

Objectives: To investigate in depth the metabolic effects of oestradiol-17 beta both alone and in combination with the progestagen dydrogesterone., Methods: Fifteen hysterectomised postmenopausal women were studied before treatment and after 24 weeks taking oestradiol-17 beta alone (2 mg per day), then following a further 6 (oestrogen-alone phase) and 12 (oestrogen plus progestagen phase) weeks with inclusion of dydrogesterone (10 mg per day for days 17-28 of each 28 day cycle). Measurements at each visit included fasting serum lipid and lipoprotein concentrations, insulin sensitivity, secretion and elimination by modelling analysis of intravenous glucose tolerance test glucose, insulin and C-peptide concentrations, body fat distribution by dual-energy X-ray absorptiometry (DXA) and arterial function by carotid artery ultrasound., Results: Significant reductions were seen throughout in total and LDL cholesterol. The net reductions in total and LDL cholesterol by the end of the study were 5.8% (P<0.05) and 18.4% (P<0.001), respectively. HDL and HDL subfraction cholesterol concentrations rose during treatment with oestradiol alone, the rise being primarily in the HDL(2) subfraction (+21.6%, P<0.001). Fasting serum triglycerides rose 30% on oestradiol treatment. These increases were unaffected by the addition of dydrogesterone. Insulin sensitivity, secretion and elimination, body fat distribution and arterial function were not significantly affected at any stage of the therapy., Conclusions: The small study sample and high variability in measures of glucose and insulin metabolism may have contributed to the absence of the expected significant improvement in these parameters. Orally administered oestradiol had beneficial effects on total, LDL and HDL cholesterol which were unaffected by the addition of dydrogesterone.

Few studies have examined the effects of 17beta-estradiol on parameters of insulin and glucose metabolism. We studied 42 healthy, untreated postmenopausal women seeking relief from menopausal symptoms. They were randomized to receive either oral 17beta-estradiol 2 mg daily combined with sequential oral norethindrone acetate (NETA) 1 mg daily from days 12 to 22, or transdermal 17beta-estradiol 0.05 mg daily combined with sequential oral NETA 1 mg daily from days 17 to 28. Intravenous glucose tolerance tests (IVGTTs) were performed at baseline and after 46 weeks (estrogen-alone phase) and 48 weeks (combined phase) of completed therapy. Mathematical modeling analysis of plasma glucose, insulin, and C-peptide concentration profiles provided measures of insulin resistance, secretion, and elimination. Both types of therapy were associated with a decrease in fasting insulin and glucose levels. Insulin sensitivity was increased by oral estradiol during the estrogen-alone phase but was reversed by the addition of NETA. Transdermal estradiol did not affect insulin sensitivity. Hepatic insulin uptake and insulin secretion were increased with both types of treatment. The oral regimen of estradiol therapy was favorable to both insulin elimination and sensitivity. Transdermal estradiol therapy had relatively few effects on insulin metabolism.

Objective: To assess the tolerance to and patient acceptability of a placebo intravaginal ring in hysterectomized, postmenopausal women over a 28-day period., Design: Open, single-center., Setting: University hospital specialist menopause clinic., Participants: A total of 24 healthy postmenopausal women attending menopause clinics at King's College Hospital and the Amarant Centre, London., Main Outcome Measures: Discomfort, ring expulsions, bowel, urinary and sexual difficulties associated with the ring and women's overall views on this method., Results: The major problems with use of the intravaginal ring were patient discomfort, involuntary ring expulsion and sexual partner discomfort. These were experienced by 13, 11 and seven women and their partners, respectively, and resulted in premature discontinuation by three women who suffered discomfort and two women who experienced recurrent involuntary ring expulsion., Conclusions: Two-thirds of the patients found the intravaginal ring acceptable, one-third did not.