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Science of Healthy Aging in Women – Multiple Choice Answers for Vol. 27, No. 5
Best Practice & Research Clinical Obstetrics and Gynaecology 27 (2013) A9–A15
Contents lists available at ScienceDirect
Best Practice & Research Clinical Obstetrics and Gynaecology journal homepage: www.elsevier.com/locate/bpobgyn
Science of Healthy Aging in Women – Multiple Choice Answers for Vol. 27, No. 5 1. a) T b) F c) T d) F e) T In 1900, in Europe, life expectancy was around 45 years and health expectancy, the ability to live independently, was similar between men and women as one died within days, weeks or months from infectious diseases. In the 20th century, preventive strategies in the public health domain (i.e. clean water, sanitation, vaccination, and medical advances increased health and life expectancy. Noncommunicable diseases became the main cause of mortality. In the 21st century a gap between health expectancy and life expectancy occurred, composed of disability and frailty. Life expectancy increased more than health expectancy 2. a) F b) F
c) T d) F e) T
Vaccination is a primary prevention strategy as it used to prevent the development of a disease. Primary prevention of colorectal cancer is accomplished by life-style factors, such as limiting obesity and excessive alcohol consumption. Colonoscopy is a secondary prevention strategy since it may recognise the development of colon cancer and may help to decide on its management. Mammography is a secondary prevention strategy also as it may recognises the development of breast cancer and may help to decide on its management. Primary prevention of osteoporosis would be due to lifestyle factors to prevent it occurring in the first place e.g. weight bearing exercise. Reducing exposure to tobacco to the lung, oral cavity and pharynx to decrease respiratory cancers is a primary prevention strategy as it may prevent the disease. 3. a) T b) T c) F
d) F e) F
Since the publication of the Women’s Health Initiative in 2002, a rapid worldwide decrease of hormone replacement therapy use took place. A reduction of hormone replacement therapy use may result in an increased incidence of osteoporosis. Women who discontinue hormone replacement therapy should be advised about rapid bone loss after use, and given other potential treatment options. Although hormone replacement therapy has shown no protective effects in the presence of established atherosclerotic disease, it may have beneficial or neutral effects on healthy vasculature or early atherosclerosis. Regarding CVA there again is at best a neutral effect. Only nulliparity, younger age of menarche, older age at menopause, late age at first birth, and infertility are known potential risk factors for breast cancer. The decreased use of hormone replacement therapy use did not influence the breast cancer rate
DOI of original article: http://dx.doi.org/10.1016/j.bpobgyn.2013.08.003. 1521-6934/$ – see front matter http://dx.doi.org/10.1016/j.bpobgyn.2013.08.004
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Appendix / Best Practice & Research Clinical Obstetrics and Gynaecology 27 (2013) A9–A15
4. a) F b) F c) F
d) T e) F
Loss of muscle mass progresses at around 0.5 % per year from the age of 30 years until the age of 50 years, at which point it accelerates to between 1 to 1.4% per year. 5. a) F b) T c) F
d) T e) F
NSAIDs have an inhibitory effect on myo-anabolic responses in all age groups though the effect may be greater in the elderly. 6. a) F b) F c) F
d) F e) T
No steroid treatments have been shown to prevent sarcopaenia in men or women. 7. a) T b) F
c) F d) F e) T
Women with CAD are generally about 10 years older than men, but they carry a greater burden of risk factors, and have a higher prevalence of symptoms, ischaemia and mortality relative to men. Elderly women with hypertension and young smokers are prominent at-risk subsets. Women with IHD are less likely than men to present with typical angina. They are more likely to experience atypical chest pain and may not perceive the symptoms as cardiac in origin. Women with IHD are also more likely to initially present with chest pain than a more clearly defined cardiac event, such as myocardial infarction. Diabetes seems to be the most important risk factor predicting significant CAD and increased mortality in women. 8. a) F b) T c) F
d) F e) T
The ETT has a higher false-positive rate in women, mainly as a result of limitations of the accuracy of the ECG in women. Current guidelines for investigating chest pain in women recommend the use of ETT as the initial preferred method. In practice, however, significant variation exists in the use of ETT as an initial diagnostic strategy. On that basis, therefore further testing would be necessary. It is not, however, contraindicated. Evidence shows, and there is much agreement that stress echocardiography is a better option than conventional ETT for risk assessment and prognosis in women at intermediate or high probability of CAD. ECG ETT, however is not useful in people with baseline ECG abnormalities (i.e. pre-excitation syndrome, electronically paced ventricular rhythm, more than 1 mm ST segment depression at rest, or left bundle branch block). Normal coronaries or non-significant CAD were more common in women than men across all age groups (especially among younger women) in a study of 12,200 patients with stable chest pain that were referred for a first-time elective diagnostic coronary angiography between 2006 and 2008. Although historically cardiac syndrome X (triad of chest pain, abnormal stress testing and unobstructed arteries) has been considered a benign condition, recent data from the WISE study suggest relatively high risk for major adverse cardiac events in the subgroup of women with cardiac syndrome X with micro-vascular coronary dysfunction. Undoubtedly, these women require further appropriate investigations and aggressive risk-factor management rather than simply reassurance that was offered in the past. The value of increasing CAC testing in predicting cardiovascular and all-cause mortality has been established in a number of studies and this is reflected in the current European Society of Cardiology and American Heart Association guidelines. These recommend carrying out CAC testing in women with an intermediate risk of IHD. 9. a) F b) F c) T d) T e) F Recent studies have shown that HRT started over a decade after the menopause may lead to increased cardiovascular risk. A possible explanation is that first pass liver metabolism of oral oestrogens increases thrombotic factors and decreases thrombolytic factor synthesis, which may accelerate thrombosis of pre-existing coronary plaque and lead to increased risk of developing venous
Appendix / Best Practice & Research Clinical Obstetrics and Gynaecology 27 (2013) A9–A15
A11
thromboembolism or stroke. In a study of 309 women with verified coronary artery disease at baseline, women were randomised to receiving unopposed oestrogen, oestrogen plus medroxyprogesterone acetate or placebo and were followed up with coronary angiography after 3 years. HRT did not slow down disease progression in women with established CAD. Current evidence suggests that HRT started closer to the age of menopause may have a cardio-protective effect only after several years of treatment. The beneficial effects of oestrogen on lipid metabolism, endothelial function and other factors involved in the pathogenesis and progression of coronary atherosclerosis are established. One possibility is that oestrogen has pro-inflammatory effects that offset its beneficial effects. HRT is not recommended for primary or secondary prevention of CAD; women and their clinicians should use forms of prevention of CAD that are already established. Oestrogen carries benefits as well as risks; evidence shows that HRT started close to the age of menopause may have a cardio-protective effect, only evident after several years of treatment, whereas HRT started over a decade after menopause may actually lead to higher risk of thrombosis and coronary atherosclerosis. HRT is currently recommended only for symptomatic women, close to the age of menopause and the use of the lowest effective dose for the shortest duration of time is advised. 10. a) F b) F
c) T d) T e) F
Pessaries are an inexpensive, simple, low-risk, and effective conservative treatment, and should be offered as a first-line treatment for the management of POP regardless of age or prolapse severity. Contraindications for the use of pessaries are non-compliance with follow up, dementia, active vaginal infection, persistent vaginal erosion or ulceration, or severe vaginal atrophy. It is important to counsel women that sexual intercourse is precluded after colpocleisis. Colpocleisis is less invasive, requires shorter operative times and less anaesthesia, and has fewer surgical risks compared with other vaginal reconstructive procedures. Thus, colpocleisis is suitable for women of advanced age, women with significant medical comorbidities, and in women who have declined or have failed conservative treatment (e.g. pessary). The US Food and Drug Administration (FDA) states that ‘based on an updated analysis of adverse events reported to the FDA and complications described in the scientific literature, the FDA identified surgical mesh for transvaginal repair of POP as an area of continuing serious concern’. 11. a) T b) F c) F d) F e) F Fever from a urinary source is three times more frequent in people with a chronic catheter. Increased mortality has been reported in elderly people with chronic indwelling catheters. These people, however, have greater functional impairment and more co-morbidities, so decreased survival is expected and the excess mortality is not attributable to urinary infection. Bacteriuria features in almost all individuals with a chronic catheter. People with indwelling catheters should have them replaced before starting treatment for symptomatic UTI. Urinary catheters in nursing-home residents should be avoided for the management of incontinence. 12. a) T b) T c) T d) F e) F Elderly people may ignore calls to defecate, leading to fecal retention. Chronic retention can lead to suppression of rectal sensation, which decreases the desire to defecate. Factors that affect bowel function are drugs (side-effects), defecatory dysfunction, degenerative disease, low dietary intake, dementia, decreased mobility, dependence on others for assistance, lack of privacy, dehydration and depression. Stimulant laxatives promote intestinal motility and do not seem to increase risks of bowel injury. High doses of polyethylene glycol may produce excessive stool frequency, especially in elderly people, and nausea, abdominal bloating, cramping, and flatulence. Stool softeners are of limited overall efficacy. 13. a) T b) T c) F
d) T e) T
Lack of mobility in elderly people is one of the primary contributing factors, by preventing them from getting to the toilet. In the Women’s Health Initiative study, hormone replacement therapy was associated with an increased incidence of all types of urinary incontinence at 1 year among
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Appendix / Best Practice & Research Clinical Obstetrics and Gynaecology 27 (2013) A9–A15
women who were continent at baseline. Urethral bulking injection is an appropriate treatment especially for elderly people, those who cannot undergo surgery, are taking anticoagulation treatment, desire non-surgical treatment for SUI, have recurrent or persistent SUI after an antiincontinence procedure, or have poor voiding function and may be at higher risk for postoperative voiding dysfunction. Elderly women have an increased prevalence of mixed urinary incontinence and intrinsic sphincter deficiency, which could potentially lead to a higher risk of adverse outcomes and lower success rates of MUS. The use of MUS to treat SUI in elderly people is an appropriate treatment, provided that individuals are counselled about the lower success rates as well as the higher risks of de-novo urgency. 14. a) T b) T c) T d) T e) T Blood glucose is regulated by hormones: insulin, glucagons, catecholamines, cortisol, and growth hormone. High levels of insulin result in hypoglycaemia that switches off insulin and stimulates glucagons and catecholamines followed by cortisol and growth hormone to normalise the blood glucose. Incretins are produced from intestines that stimulate insulin from the pancreas only when nutrients enter the intestine.
15. a) T b) F
c) F d) F e) F
The central nervous system can only use glucose as fuel. Skeletal muscle and adipose tissue can use glucose and ketones as fuel. Cardiac and smooth muscle can also use other fuels.
16. a) F b) T c) T
d) F e) T
Incretins are peptides produced from the intestinal mucosa when nutrients enter the intestines. These stimulate insulin secretion from pancreatic beta cells only when food is in the intestines and not in a fasting state. Glucagon, such as peptide-1, can slow the gastric emptying time and result in weight loss.
17. a) T b) T c) T d) T e) T Type 2 diabetes is as a result of insulin resistance and beta-cell damage. Beta cells are not able to produce high levels of insulin to maintain blood glucose within the normal range. Most people with type 2 diabetes are obese and have other features of metabolic syndrome, such as hypertension and hyperlipidaemia. 18. a) T b) T c) T d) T e) T Oestogen deficiency has a negative effect on collagen, which in turn is found in all the above mentioned structures. 19. a) T b) T c) T d) T e) T With ageing, the level of the transcription factor c-jun increases, whereas the level of c-fos remains the same, as found in young skin. In contrast, other investigators have reported that even the transcription factor c-fos is found in higher amounts in old skin compared with young skin. These two transcription factors enhance the formation of activator protein-1 (AP-1). This protein triggers the expression of MMP genes and consequently the levels of MMPs, especially MMP-1 and MMP-9 are higher compared with levels in young skin. These MMPs increase the synthesis of collagenases and gelatinases, the enzymes that breakdown collagen. Exposure to ultraviolet radiation accelerates these processes
Appendix / Best Practice & Research Clinical Obstetrics and Gynaecology 27 (2013) A9–A15
A13
20. a) T b) T c) T d) T e) T External stimuli, such as cigarette smoke and ultraviolet radiation, together with internal stimuli, such as psychological stress and hormone changes that accompany the menopause, induce nerve endings to release various neuropeptides into the skin. These neuropeptides increase the synthesis of adhesion molecules, which are responsible for the first step in the inflammatory process. Adhesion molecules enable circulating monocytes and granulocytes to roll over, adhere and diapedese through the endothelial wall of blood vessels and migrate into the dermis. These white blood cells produce and secrete proteases and reactive oxygen species which in turn change the turnover of the proteins of the dermis and also damage cells in the skin. The damaged cells are stimulated to release leukotrienes and prostaglandins. These chemicals act as stimuli on the mast cells and induce the secretion of histamine and the cytokine tumour necrosis factor-alpha, which in turn stimulate endothelial cells to produce intra-cellular adhesion molecule-1 and also help liberate P-selectins. A second set of immune cells is stimulated to migrate, causing more inflammation and the process goes on. The final result would be an imbalance in the degradation and synthesis of elastin and collagen fibres. As the fibroblasts in old age are unable to synthesise these fibres, this inflammatory process causes ageing of the skin with a change in the composition of the dermis and epidermis, skin thickness and elastic properties of the skin
21. a) T b) T c) F
d) F e) T
Fat-free mass decreases on average by up to 40% from 20–70 years of age. The maximal fat-free mass is usually reached at 20 years of age, and the maximal fat mass at 60–70 years of age; both measures subsequently decline thereafter. Because fat mass usually increases more than the decrease in fat free mass after age 20 years, both body weight and BMI usually increase until age 50–59 years of age; thereafter, they decrease owing to the parallel decrease in fat mass and fat free mass. The maximal fatfree mass has usually been reached at around 20 years of age in both men and women. The decline thereafter could be counteracted by an active life with regular physical activity. BMI (weight in kilos divided by the square of the body length in meters) is a commonly used measure but is not the best to monitor visceral adipose tissue. Waist circumference is a better measure, but sagittal abdominal diameter shows the strongest correlation to visceral adipose tissue irrespective of age, sex, and the degree of obesity. Being overweight and obese accounts for about two-thirds of cases of type 2 diabetes.
22. a) F b) T c) F d) T e) F Abdominal obesity is a well-established phenotypic companion of a cluster of metabolic abnormalities characterised by insulin resistance and abdominal obesity, and is the best obesityrelated predictor of type 2 diabetes. Waist circumference is currently the most commonly used measure of abdominal obesity, and it is highly associated with, for example, cardiovascular disease. Increased body weight is associated with increased death rates for all cancers combined, and for cancers at multiple specific sites. The heaviest men and women (BMI of at least 40.0) in a large prospectively studied cohort had death rates from all cancers that were 52% and 62%, respectively, than the rates in men and women of normal weight. In menopausal women, obesity confers a lower risk of osteoporosis, probably owing to combined effects of weight-bearing and aromatisation of adrenal androgens to oestrogens affecting bone metabolism. Sarcopenia, defined as a syndrome rather than as a pathology, is the loss of muscle mass and function associated with normal ageing. The factors that contribute to the development of sarcopenia in elderly people are the state of chronic inflammation; atrophy of motor neurones; and reduced protein intake and immobility. Sarcopenia is associated with adverse clinical outcomes like mobility limitations, functional impairment and fractures.
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Appendix / Best Practice & Research Clinical Obstetrics and Gynaecology 27 (2013) A9–A15
23. a) F b) T c) T
d) T e) F
Most analyses have shown at least a 50% reduction in mortality among highly fit people compared with low fit people. People with moderate to high levels of physical activity have lower mortality rate than those with lower levels of activity. Physical activity prevents a number of malignant diseases such as the highly prevalent breast and prostate cancers and also prevents cardiovascular disease by means of effects on a number of risk factors. For example a meta-analysis showed significant decrease in blood pressure, body fat and triglycerides in groups of normotensive or pre-hypertensive adults by dynamic resistance training. Apart from several ways of retrieving self-reported data, physical activity levels may be measured and defined by pedometers that are simple and inexpensive sensors used to assess and motivate physical activity behaviours in clinical practice. The correct classification of pedometer measured activity is provided. Although physical activity affects the immune system it has not yet been shown that regular physical activity affects the mechanisms behind rheumatoid arthritis and multiple sclerosis 24. a) F b) T c) T
d) F e) F
Body water decreases with age, reducing the volume of distribution and increasing the plasma concentration of water soluble drugs such as aminoglycosides. With ageing, a 15–30% reduction in liver mass can reduce drug clearance. Body fat composition increases by 20–40% with ageing. Increased fat forms a reservoir for lipid soluble drugs, which can increase their elimination half life and prolong drug action. With ageing alone, eGFR falls by about 1 ml/min/1.73 m2 per year. Hence, this woman may have lost 25 but not 45 ml/min/1.73 m2. Elderly people are, however, at risk of renal damage owing to concomitant disease such as diabetes and hypertension, and drugs such as non-steroidal inflammatory drugs, which may accelerate renal decline. Reduced expression and sensitivity of many receptors and impairment of downstream signalling occurs with ageing. This can reduce efficacy of drugs and increase sensitivity to side-effects in elderly people. 25. a) F b) T c) F
d) T e) F
Her eGFR indicates mild renal impairment at worst, so her renal function does not necessitate a dose reduction for oxybutynin. However, eGFR may be inaccurate in estimating renal function in elderly people and a creatinine clearance method of measuring renal impairment may be more accurate. The manufacturer advises caution when using oxybutynin in renal impairment. Elderly people have an increased risk of central nervous system side-effects from a number of drugs, including antimuscarinics, opioids, benzodiazepines and general anaesthesia caused by changes in brain size, composition, receptor expression, and permeability of the blood–brain barrier to drugs. This patient has vascular dementia and may be particularly susceptible. Oxybutynin does not alter hepatic drug metabolism so will not interfere with warfarin metabolism. Anti-muscarinics do not seem to interact with warfarin. The vagus nerve acts on the sino-atrial (SA) and atrio-ventricular (AV) nodes to slow the heart via muscarinic receptors. Anti-muscarinic drugs inhibit the action of the vagus nerve on the heart and cause tachycardia. Elderly people are generally more, rather than less, susceptible to the adverse effects of drugs resulting from altered physiology with ageing, co-morbidities, frailty and concomitant medications. For example, this patient may be particularly at risk of dry mouth because of coexisting diabetes and furosemide treatment, and constipation caused by reduced colonic transit, poor oral intake, and general frailty. Addition of an anti-muscarinic could, therefore, trigger these side-effects more easily than in a younger person. 26. a) F b) F c) F
d) F e) T
Analgesia is an important priority for all patients who need it, and morphine is rarely absolutely contraindicated. Individuals undergo physiological ageing at different rates and biological rather than chronological ageing will determine how an individual handles and responds to morphine. Age alone is not a contraindication to patient-controlled analgesia (PCA). Elderly people, however, may be at
Appendix / Best Practice & Research Clinical Obstetrics and Gynaecology 27 (2013) A9–A15
A15
increased risk of morphine side-effects, require more intensive monitoring, or may have cognitive impairment, all of which could increase the risks and reduce the benefits of PCA. Elderly people require individualised assessment before prescribing decisions are made. A ‘start low, go slow’ approach is appropriate to optimise benefits and minimise harm of drugs used in chronic conditions such as hypertension and diabetes. It is inappropriate, however, in acute care where management of pain, infection or other acute problems may be delayed. Ensure a sufficient loading dose, consider increasing dose intervals rather than reducing dose to maintain efficacy and minimise side-effects, and monitor intensively. Morphine is metabolised in the liver to active metabolites and both morphine and its metabolites are excreted by the kidney. Renal impairment thus has a greater effect on morphine plasma levels than hepatic impairment, and is the greater risk factor for opiate toxicity. Elderly people are particularly at risk of central nervous system side-effects of drugs, such as anaesthetic agents and morphine. Drugs should always be considered as a potential cause of post-operative delirium. 27. a) T b) T c) F
d) F e) F
Clinical trial evidence to support use of medicines in elderly people is less robust than in younger people. For example, older people with ovarian cancer have been under-represented in clinical trials. Elderly people may be excluded from trials by design, because of age, co-morbidity or polypharmacy, or by default, where functional limitation prevents participation. With ageing, a decrease in cell proliferation occurs that may be mediated by defects in growth factor receptor and signal transduction. This particularly affects organs and tissues with relatively fast cell turnover, including the bone marrow, gastrointestinal mucosa, skin and hair. Elderly people are thus increasingly susceptible to haematological, gastrointestinal and other side-effects of anticancer chemotherapy, which may limit its application. Polypharmacy can be defined as the concurrent use of five or more prescribed medicines or ‘use of more medicines than are clinically indicated’. This patient is on three antihypertensive medications but has low blood pressure. She is taking iron despite normal haemoglobin. Some of her medications should be stopped and stop dates should always be set or discussed when starting new medications. Hypertension, diabetes mellitus and osteoarthritis are not specific contraindications to cancer chemotherapy. They can, however, predispose to cardiovascular disease, which may prevent the use of anthracyclines and other cytotoxic antibiotics. Frailty is defined as increased vulnerability to environmental factors. Some characteristics include unintentional weight loss (10 lbs in past year), selfreported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. This lady is fully independent and does not seem to be frail. 28. a) T b) F c) F d) F e) F Aromatase is involved in steroidogenesis, catalysing the conversion of androgens into oestrogens as it plays a crucial role in physiological processes, such as control of reproduction and neuroprotection. The only sources of oestrogen are androgens made in the ovary and adrenals subsequently converted to oestrogen in fat tissue. 29. a) T b) F c) F d) F e) F Oestrogen may limit inflammation and regulate the presence of insoluble amyloid beta. There is no convincing evidence that it increases tau protein, induces neuronal damage or causes neurotransmitter imbalance.
Contents lists available at ScienceDirect
Best Practice & Research Clinical Obstetrics and Gynaecology journal homepage: www.elsevier.com/locate/bpobgyn
Science of Healthy Aging in Women – Multiple Choice Answers for Vol. 27, No. 5 1. a) T b) F c) T d) F e) T In 1900, in Europe, life expectancy was around 45 years and health expectancy, the ability to live independently, was similar between men and women as one died within days, weeks or months from infectious diseases. In the 20th century, preventive strategies in the public health domain (i.e. clean water, sanitation, vaccination, and medical advances increased health and life expectancy. Noncommunicable diseases became the main cause of mortality. In the 21st century a gap between health expectancy and life expectancy occurred, composed of disability and frailty. Life expectancy increased more than health expectancy 2. a) F b) F
c) T d) F e) T
Vaccination is a primary prevention strategy as it used to prevent the development of a disease. Primary prevention of colorectal cancer is accomplished by life-style factors, such as limiting obesity and excessive alcohol consumption. Colonoscopy is a secondary prevention strategy since it may recognise the development of colon cancer and may help to decide on its management. Mammography is a secondary prevention strategy also as it may recognises the development of breast cancer and may help to decide on its management. Primary prevention of osteoporosis would be due to lifestyle factors to prevent it occurring in the first place e.g. weight bearing exercise. Reducing exposure to tobacco to the lung, oral cavity and pharynx to decrease respiratory cancers is a primary prevention strategy as it may prevent the disease. 3. a) T b) T c) F
d) F e) F
Since the publication of the Women’s Health Initiative in 2002, a rapid worldwide decrease of hormone replacement therapy use took place. A reduction of hormone replacement therapy use may result in an increased incidence of osteoporosis. Women who discontinue hormone replacement therapy should be advised about rapid bone loss after use, and given other potential treatment options. Although hormone replacement therapy has shown no protective effects in the presence of established atherosclerotic disease, it may have beneficial or neutral effects on healthy vasculature or early atherosclerosis. Regarding CVA there again is at best a neutral effect. Only nulliparity, younger age of menarche, older age at menopause, late age at first birth, and infertility are known potential risk factors for breast cancer. The decreased use of hormone replacement therapy use did not influence the breast cancer rate
DOI of original article: http://dx.doi.org/10.1016/j.bpobgyn.2013.08.003. 1521-6934/$ – see front matter http://dx.doi.org/10.1016/j.bpobgyn.2013.08.004
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Appendix / Best Practice & Research Clinical Obstetrics and Gynaecology 27 (2013) A9–A15
4. a) F b) F c) F
d) T e) F
Loss of muscle mass progresses at around 0.5 % per year from the age of 30 years until the age of 50 years, at which point it accelerates to between 1 to 1.4% per year. 5. a) F b) T c) F
d) T e) F
NSAIDs have an inhibitory effect on myo-anabolic responses in all age groups though the effect may be greater in the elderly. 6. a) F b) F c) F
d) F e) T
No steroid treatments have been shown to prevent sarcopaenia in men or women. 7. a) T b) F
c) F d) F e) T
Women with CAD are generally about 10 years older than men, but they carry a greater burden of risk factors, and have a higher prevalence of symptoms, ischaemia and mortality relative to men. Elderly women with hypertension and young smokers are prominent at-risk subsets. Women with IHD are less likely than men to present with typical angina. They are more likely to experience atypical chest pain and may not perceive the symptoms as cardiac in origin. Women with IHD are also more likely to initially present with chest pain than a more clearly defined cardiac event, such as myocardial infarction. Diabetes seems to be the most important risk factor predicting significant CAD and increased mortality in women. 8. a) F b) T c) F
d) F e) T
The ETT has a higher false-positive rate in women, mainly as a result of limitations of the accuracy of the ECG in women. Current guidelines for investigating chest pain in women recommend the use of ETT as the initial preferred method. In practice, however, significant variation exists in the use of ETT as an initial diagnostic strategy. On that basis, therefore further testing would be necessary. It is not, however, contraindicated. Evidence shows, and there is much agreement that stress echocardiography is a better option than conventional ETT for risk assessment and prognosis in women at intermediate or high probability of CAD. ECG ETT, however is not useful in people with baseline ECG abnormalities (i.e. pre-excitation syndrome, electronically paced ventricular rhythm, more than 1 mm ST segment depression at rest, or left bundle branch block). Normal coronaries or non-significant CAD were more common in women than men across all age groups (especially among younger women) in a study of 12,200 patients with stable chest pain that were referred for a first-time elective diagnostic coronary angiography between 2006 and 2008. Although historically cardiac syndrome X (triad of chest pain, abnormal stress testing and unobstructed arteries) has been considered a benign condition, recent data from the WISE study suggest relatively high risk for major adverse cardiac events in the subgroup of women with cardiac syndrome X with micro-vascular coronary dysfunction. Undoubtedly, these women require further appropriate investigations and aggressive risk-factor management rather than simply reassurance that was offered in the past. The value of increasing CAC testing in predicting cardiovascular and all-cause mortality has been established in a number of studies and this is reflected in the current European Society of Cardiology and American Heart Association guidelines. These recommend carrying out CAC testing in women with an intermediate risk of IHD. 9. a) F b) F c) T d) T e) F Recent studies have shown that HRT started over a decade after the menopause may lead to increased cardiovascular risk. A possible explanation is that first pass liver metabolism of oral oestrogens increases thrombotic factors and decreases thrombolytic factor synthesis, which may accelerate thrombosis of pre-existing coronary plaque and lead to increased risk of developing venous
Appendix / Best Practice & Research Clinical Obstetrics and Gynaecology 27 (2013) A9–A15
A11
thromboembolism or stroke. In a study of 309 women with verified coronary artery disease at baseline, women were randomised to receiving unopposed oestrogen, oestrogen plus medroxyprogesterone acetate or placebo and were followed up with coronary angiography after 3 years. HRT did not slow down disease progression in women with established CAD. Current evidence suggests that HRT started closer to the age of menopause may have a cardio-protective effect only after several years of treatment. The beneficial effects of oestrogen on lipid metabolism, endothelial function and other factors involved in the pathogenesis and progression of coronary atherosclerosis are established. One possibility is that oestrogen has pro-inflammatory effects that offset its beneficial effects. HRT is not recommended for primary or secondary prevention of CAD; women and their clinicians should use forms of prevention of CAD that are already established. Oestrogen carries benefits as well as risks; evidence shows that HRT started close to the age of menopause may have a cardio-protective effect, only evident after several years of treatment, whereas HRT started over a decade after menopause may actually lead to higher risk of thrombosis and coronary atherosclerosis. HRT is currently recommended only for symptomatic women, close to the age of menopause and the use of the lowest effective dose for the shortest duration of time is advised. 10. a) F b) F
c) T d) T e) F
Pessaries are an inexpensive, simple, low-risk, and effective conservative treatment, and should be offered as a first-line treatment for the management of POP regardless of age or prolapse severity. Contraindications for the use of pessaries are non-compliance with follow up, dementia, active vaginal infection, persistent vaginal erosion or ulceration, or severe vaginal atrophy. It is important to counsel women that sexual intercourse is precluded after colpocleisis. Colpocleisis is less invasive, requires shorter operative times and less anaesthesia, and has fewer surgical risks compared with other vaginal reconstructive procedures. Thus, colpocleisis is suitable for women of advanced age, women with significant medical comorbidities, and in women who have declined or have failed conservative treatment (e.g. pessary). The US Food and Drug Administration (FDA) states that ‘based on an updated analysis of adverse events reported to the FDA and complications described in the scientific literature, the FDA identified surgical mesh for transvaginal repair of POP as an area of continuing serious concern’. 11. a) T b) F c) F d) F e) F Fever from a urinary source is three times more frequent in people with a chronic catheter. Increased mortality has been reported in elderly people with chronic indwelling catheters. These people, however, have greater functional impairment and more co-morbidities, so decreased survival is expected and the excess mortality is not attributable to urinary infection. Bacteriuria features in almost all individuals with a chronic catheter. People with indwelling catheters should have them replaced before starting treatment for symptomatic UTI. Urinary catheters in nursing-home residents should be avoided for the management of incontinence. 12. a) T b) T c) T d) F e) F Elderly people may ignore calls to defecate, leading to fecal retention. Chronic retention can lead to suppression of rectal sensation, which decreases the desire to defecate. Factors that affect bowel function are drugs (side-effects), defecatory dysfunction, degenerative disease, low dietary intake, dementia, decreased mobility, dependence on others for assistance, lack of privacy, dehydration and depression. Stimulant laxatives promote intestinal motility and do not seem to increase risks of bowel injury. High doses of polyethylene glycol may produce excessive stool frequency, especially in elderly people, and nausea, abdominal bloating, cramping, and flatulence. Stool softeners are of limited overall efficacy. 13. a) T b) T c) F
d) T e) T
Lack of mobility in elderly people is one of the primary contributing factors, by preventing them from getting to the toilet. In the Women’s Health Initiative study, hormone replacement therapy was associated with an increased incidence of all types of urinary incontinence at 1 year among
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Appendix / Best Practice & Research Clinical Obstetrics and Gynaecology 27 (2013) A9–A15
women who were continent at baseline. Urethral bulking injection is an appropriate treatment especially for elderly people, those who cannot undergo surgery, are taking anticoagulation treatment, desire non-surgical treatment for SUI, have recurrent or persistent SUI after an antiincontinence procedure, or have poor voiding function and may be at higher risk for postoperative voiding dysfunction. Elderly women have an increased prevalence of mixed urinary incontinence and intrinsic sphincter deficiency, which could potentially lead to a higher risk of adverse outcomes and lower success rates of MUS. The use of MUS to treat SUI in elderly people is an appropriate treatment, provided that individuals are counselled about the lower success rates as well as the higher risks of de-novo urgency. 14. a) T b) T c) T d) T e) T Blood glucose is regulated by hormones: insulin, glucagons, catecholamines, cortisol, and growth hormone. High levels of insulin result in hypoglycaemia that switches off insulin and stimulates glucagons and catecholamines followed by cortisol and growth hormone to normalise the blood glucose. Incretins are produced from intestines that stimulate insulin from the pancreas only when nutrients enter the intestine.
15. a) T b) F
c) F d) F e) F
The central nervous system can only use glucose as fuel. Skeletal muscle and adipose tissue can use glucose and ketones as fuel. Cardiac and smooth muscle can also use other fuels.
16. a) F b) T c) T
d) F e) T
Incretins are peptides produced from the intestinal mucosa when nutrients enter the intestines. These stimulate insulin secretion from pancreatic beta cells only when food is in the intestines and not in a fasting state. Glucagon, such as peptide-1, can slow the gastric emptying time and result in weight loss.
17. a) T b) T c) T d) T e) T Type 2 diabetes is as a result of insulin resistance and beta-cell damage. Beta cells are not able to produce high levels of insulin to maintain blood glucose within the normal range. Most people with type 2 diabetes are obese and have other features of metabolic syndrome, such as hypertension and hyperlipidaemia. 18. a) T b) T c) T d) T e) T Oestogen deficiency has a negative effect on collagen, which in turn is found in all the above mentioned structures. 19. a) T b) T c) T d) T e) T With ageing, the level of the transcription factor c-jun increases, whereas the level of c-fos remains the same, as found in young skin. In contrast, other investigators have reported that even the transcription factor c-fos is found in higher amounts in old skin compared with young skin. These two transcription factors enhance the formation of activator protein-1 (AP-1). This protein triggers the expression of MMP genes and consequently the levels of MMPs, especially MMP-1 and MMP-9 are higher compared with levels in young skin. These MMPs increase the synthesis of collagenases and gelatinases, the enzymes that breakdown collagen. Exposure to ultraviolet radiation accelerates these processes
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20. a) T b) T c) T d) T e) T External stimuli, such as cigarette smoke and ultraviolet radiation, together with internal stimuli, such as psychological stress and hormone changes that accompany the menopause, induce nerve endings to release various neuropeptides into the skin. These neuropeptides increase the synthesis of adhesion molecules, which are responsible for the first step in the inflammatory process. Adhesion molecules enable circulating monocytes and granulocytes to roll over, adhere and diapedese through the endothelial wall of blood vessels and migrate into the dermis. These white blood cells produce and secrete proteases and reactive oxygen species which in turn change the turnover of the proteins of the dermis and also damage cells in the skin. The damaged cells are stimulated to release leukotrienes and prostaglandins. These chemicals act as stimuli on the mast cells and induce the secretion of histamine and the cytokine tumour necrosis factor-alpha, which in turn stimulate endothelial cells to produce intra-cellular adhesion molecule-1 and also help liberate P-selectins. A second set of immune cells is stimulated to migrate, causing more inflammation and the process goes on. The final result would be an imbalance in the degradation and synthesis of elastin and collagen fibres. As the fibroblasts in old age are unable to synthesise these fibres, this inflammatory process causes ageing of the skin with a change in the composition of the dermis and epidermis, skin thickness and elastic properties of the skin
21. a) T b) T c) F
d) F e) T
Fat-free mass decreases on average by up to 40% from 20–70 years of age. The maximal fat-free mass is usually reached at 20 years of age, and the maximal fat mass at 60–70 years of age; both measures subsequently decline thereafter. Because fat mass usually increases more than the decrease in fat free mass after age 20 years, both body weight and BMI usually increase until age 50–59 years of age; thereafter, they decrease owing to the parallel decrease in fat mass and fat free mass. The maximal fatfree mass has usually been reached at around 20 years of age in both men and women. The decline thereafter could be counteracted by an active life with regular physical activity. BMI (weight in kilos divided by the square of the body length in meters) is a commonly used measure but is not the best to monitor visceral adipose tissue. Waist circumference is a better measure, but sagittal abdominal diameter shows the strongest correlation to visceral adipose tissue irrespective of age, sex, and the degree of obesity. Being overweight and obese accounts for about two-thirds of cases of type 2 diabetes.
22. a) F b) T c) F d) T e) F Abdominal obesity is a well-established phenotypic companion of a cluster of metabolic abnormalities characterised by insulin resistance and abdominal obesity, and is the best obesityrelated predictor of type 2 diabetes. Waist circumference is currently the most commonly used measure of abdominal obesity, and it is highly associated with, for example, cardiovascular disease. Increased body weight is associated with increased death rates for all cancers combined, and for cancers at multiple specific sites. The heaviest men and women (BMI of at least 40.0) in a large prospectively studied cohort had death rates from all cancers that were 52% and 62%, respectively, than the rates in men and women of normal weight. In menopausal women, obesity confers a lower risk of osteoporosis, probably owing to combined effects of weight-bearing and aromatisation of adrenal androgens to oestrogens affecting bone metabolism. Sarcopenia, defined as a syndrome rather than as a pathology, is the loss of muscle mass and function associated with normal ageing. The factors that contribute to the development of sarcopenia in elderly people are the state of chronic inflammation; atrophy of motor neurones; and reduced protein intake and immobility. Sarcopenia is associated with adverse clinical outcomes like mobility limitations, functional impairment and fractures.
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23. a) F b) T c) T
d) T e) F
Most analyses have shown at least a 50% reduction in mortality among highly fit people compared with low fit people. People with moderate to high levels of physical activity have lower mortality rate than those with lower levels of activity. Physical activity prevents a number of malignant diseases such as the highly prevalent breast and prostate cancers and also prevents cardiovascular disease by means of effects on a number of risk factors. For example a meta-analysis showed significant decrease in blood pressure, body fat and triglycerides in groups of normotensive or pre-hypertensive adults by dynamic resistance training. Apart from several ways of retrieving self-reported data, physical activity levels may be measured and defined by pedometers that are simple and inexpensive sensors used to assess and motivate physical activity behaviours in clinical practice. The correct classification of pedometer measured activity is provided. Although physical activity affects the immune system it has not yet been shown that regular physical activity affects the mechanisms behind rheumatoid arthritis and multiple sclerosis 24. a) F b) T c) T
d) F e) F
Body water decreases with age, reducing the volume of distribution and increasing the plasma concentration of water soluble drugs such as aminoglycosides. With ageing, a 15–30% reduction in liver mass can reduce drug clearance. Body fat composition increases by 20–40% with ageing. Increased fat forms a reservoir for lipid soluble drugs, which can increase their elimination half life and prolong drug action. With ageing alone, eGFR falls by about 1 ml/min/1.73 m2 per year. Hence, this woman may have lost 25 but not 45 ml/min/1.73 m2. Elderly people are, however, at risk of renal damage owing to concomitant disease such as diabetes and hypertension, and drugs such as non-steroidal inflammatory drugs, which may accelerate renal decline. Reduced expression and sensitivity of many receptors and impairment of downstream signalling occurs with ageing. This can reduce efficacy of drugs and increase sensitivity to side-effects in elderly people. 25. a) F b) T c) F
d) T e) F
Her eGFR indicates mild renal impairment at worst, so her renal function does not necessitate a dose reduction for oxybutynin. However, eGFR may be inaccurate in estimating renal function in elderly people and a creatinine clearance method of measuring renal impairment may be more accurate. The manufacturer advises caution when using oxybutynin in renal impairment. Elderly people have an increased risk of central nervous system side-effects from a number of drugs, including antimuscarinics, opioids, benzodiazepines and general anaesthesia caused by changes in brain size, composition, receptor expression, and permeability of the blood–brain barrier to drugs. This patient has vascular dementia and may be particularly susceptible. Oxybutynin does not alter hepatic drug metabolism so will not interfere with warfarin metabolism. Anti-muscarinics do not seem to interact with warfarin. The vagus nerve acts on the sino-atrial (SA) and atrio-ventricular (AV) nodes to slow the heart via muscarinic receptors. Anti-muscarinic drugs inhibit the action of the vagus nerve on the heart and cause tachycardia. Elderly people are generally more, rather than less, susceptible to the adverse effects of drugs resulting from altered physiology with ageing, co-morbidities, frailty and concomitant medications. For example, this patient may be particularly at risk of dry mouth because of coexisting diabetes and furosemide treatment, and constipation caused by reduced colonic transit, poor oral intake, and general frailty. Addition of an anti-muscarinic could, therefore, trigger these side-effects more easily than in a younger person. 26. a) F b) F c) F
d) F e) T
Analgesia is an important priority for all patients who need it, and morphine is rarely absolutely contraindicated. Individuals undergo physiological ageing at different rates and biological rather than chronological ageing will determine how an individual handles and responds to morphine. Age alone is not a contraindication to patient-controlled analgesia (PCA). Elderly people, however, may be at
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increased risk of morphine side-effects, require more intensive monitoring, or may have cognitive impairment, all of which could increase the risks and reduce the benefits of PCA. Elderly people require individualised assessment before prescribing decisions are made. A ‘start low, go slow’ approach is appropriate to optimise benefits and minimise harm of drugs used in chronic conditions such as hypertension and diabetes. It is inappropriate, however, in acute care where management of pain, infection or other acute problems may be delayed. Ensure a sufficient loading dose, consider increasing dose intervals rather than reducing dose to maintain efficacy and minimise side-effects, and monitor intensively. Morphine is metabolised in the liver to active metabolites and both morphine and its metabolites are excreted by the kidney. Renal impairment thus has a greater effect on morphine plasma levels than hepatic impairment, and is the greater risk factor for opiate toxicity. Elderly people are particularly at risk of central nervous system side-effects of drugs, such as anaesthetic agents and morphine. Drugs should always be considered as a potential cause of post-operative delirium. 27. a) T b) T c) F
d) F e) F
Clinical trial evidence to support use of medicines in elderly people is less robust than in younger people. For example, older people with ovarian cancer have been under-represented in clinical trials. Elderly people may be excluded from trials by design, because of age, co-morbidity or polypharmacy, or by default, where functional limitation prevents participation. With ageing, a decrease in cell proliferation occurs that may be mediated by defects in growth factor receptor and signal transduction. This particularly affects organs and tissues with relatively fast cell turnover, including the bone marrow, gastrointestinal mucosa, skin and hair. Elderly people are thus increasingly susceptible to haematological, gastrointestinal and other side-effects of anticancer chemotherapy, which may limit its application. Polypharmacy can be defined as the concurrent use of five or more prescribed medicines or ‘use of more medicines than are clinically indicated’. This patient is on three antihypertensive medications but has low blood pressure. She is taking iron despite normal haemoglobin. Some of her medications should be stopped and stop dates should always be set or discussed when starting new medications. Hypertension, diabetes mellitus and osteoarthritis are not specific contraindications to cancer chemotherapy. They can, however, predispose to cardiovascular disease, which may prevent the use of anthracyclines and other cytotoxic antibiotics. Frailty is defined as increased vulnerability to environmental factors. Some characteristics include unintentional weight loss (10 lbs in past year), selfreported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. This lady is fully independent and does not seem to be frail. 28. a) T b) F c) F d) F e) F Aromatase is involved in steroidogenesis, catalysing the conversion of androgens into oestrogens as it plays a crucial role in physiological processes, such as control of reproduction and neuroprotection. The only sources of oestrogen are androgens made in the ovary and adrenals subsequently converted to oestrogen in fat tissue. 29. a) T b) F c) F d) F e) F Oestrogen may limit inflammation and regulate the presence of insoluble amyloid beta. There is no convincing evidence that it increases tau protein, induces neuronal damage or causes neurotransmitter imbalance.