Guest Lectures

Rational Drug Prescription

K. Uma Kalyani1, S. Deepa2,

1Assistant Professor of Geriatric Medicine, Madras Medical College, Chennai 2Associate Professor of Geriatric Medicine, Govt. Mohan Kumaramangalam Medical College, Salem

Older people are the major consumers of both prescribed and over the counter medications. There are

age related changes in the pharmacokinetics and pharmacodynamics of medications. As there is increased

prevalence of multimorbidity among older people, they take greater number of drugs, termed as

polypharmacy.

Adverse drug reactions are more common in the older people due to age related changes in

pharmacokinetics and pharmacodynamics, multimorbidity and polypharmacy. Multimorbidity and

polypharmacy can lead to drug-drug interactions and drug-disease interactions. Adverse drug reactions

can present as geriatric syndromes such as falls, acute confusional state, etc, in older people.

Just as overuse of inappropriate drugs is common in older people, underuse of beneficial therapy also

is common in older people. Beer’s criteria, Medication appropriateness index and various methods are

available to assess the quality of prescribing in older people. Older people may have multiple health care

providers because of the multimorbidity. Lack of care coordination among multiple health care providers

may result in drug duplicity, drug interactions and adverse outcomes.

Adherence to drug therapy in older people is affected by cognitive and sensory impairments,

polypharmacy, social isolation and cost of the drug.

We have limited knowledge about the efficacy and safety of the drugs in older people because most of

the drug trials exclude older people. Pharmacogenetics and Pharmacoeconomics may guide prescription

practices in the elderly in future. Periodic review of medications and discontinuation of unnecessary

medications will be helpful in optimal and rational prescribing in older people

More than Skin Deep: Dermatological Problems in the Elderly

Dr. Anil Abraham

Consultant Dermatologist, Former Professor and Head, Department of Dermatology,

St. Johns Medical College, Bengaluru

Dermatological problems in the geriatric population range from seemingly simple pruritus to

potentially dangerous pre-cancerous and malignant lesions. Very often the skin is neglected in the elderly

patient, though it can give us a clue to several internal and metabolic problems. The talk will focus on skin

changes intrinsic to ageing, dermatological problems that arise from drugs or treatment in this age group

and issues unique to the elderly population, through a case discussion approach.

Guest Lectures 165

Current Guidelines for use of combined Anticoagulation and

Antiplatelets in Coronary Artery Disease and Atrial Fibrillation –

A Rational Approach in the Older Person

Priya Vijayakumar

Professor, Department of Geriatrics, AIMS, Kochi

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice and the prevalence

increases markedly with older age, from 0.5% at 40–50 years to 5% in those aged ≥ 65 years and almost

10% in people aged ≥ 80 years. AF is slightly more prevalent in men than in women. The lifetime risk of

developing AF aged ≥ 40 years is approximately one in four.

The Screening for Atrial Fibrillation in the Elderly (SAFE) stud is a randomized controlled trial

(RCT) of systematic screening (targeted and total population screening) compared with routine practice for

the detection of AF in people aged ≥ 65 years in the UK, which involved 15,000 patients and revealed that

the prevalence of AF was 7.2%, with a higher prevalence in men (7.8%) and those aged ≥ 75 years (10.3%).

The incidence of AF ranged from 1.04% to 1.64% per year. The incidence and prevalence of AF are

increasing and are projected to rise exponentially as the population ages and the prevalence of

cardiovascular risk factors increases.

The major complication of AF is stroke. AF is associated with a fivefold increased risk of stroke

compared with age- and sex-matched patients in sinus rhythm, and doubles the risk of stroke after

adjustment for other risk factors. In addition, when a stroke occurs in a patient with AF, it is more severe,

more likely to recur, and more likely to result in death or disability than strokes in patients without AF.

Further, stroke survivors with AF face persistent neurological deficits and permanent disability, which

have a significant negative impact on their quality of life and increase the burden of care for their family

and the health services.

There are a number of scoring systems that predict stroke in patients with atrial fibrillation, the

commonest is the CHA2DS2Vasc score.

The HAS-BLED score5 is a commonly used bleeding risk score, which includes risk factors for

bleeding during warfarin therapy.

The results of several studies indicate that therapeutic anticoagulation using oral anticoagulants is

not routinely recommended for patients with acute coronary syndrome who have another indication for

anticoagulation. Multiple studies have assessed the outcomes of warfarin and aspirin versus aspirin alone

in acute coronary syndromes. A meta analysis showed that in studies of warfarin and a target INR of 2-3,

the addition of aspirin was associated with a significant reduction of major adverse effects (all cause death,

non fatal thromboembolic stroke) but with an increased risk of bleeding.

More recent trials have studied a possible role for the newer oral anticoagulants - Rivaroxaban and

Apixiban, which have both been studied in patients with acute coronary syndromes.

In combination with aspirin the low dose of Rivaroxaban reduced the composite death from

cardiovascular causes, myocardial infarction or stroke compared to placebo. There was an increase in

intracranial hemorrhage without fatal bleeding.

The apixiban with aspirin trial was stopped early due to a significant increase in the rate of major

bleeding in the Apixiban group compare to placebo.

The European Society of Cardiology guidelines in 2015 suggested that Rivaroxaban 2.5 mg twice

daily might be considered in combination with aspirin and clopidogrel for non ST elevation MI in patients

with high ischemic risks but low bleeding risk.

Caution is needed in patients more than 75 years of age and less than 60 kg body weight.

For patients with ACS on medical management, a single anti platelet and an oral anticoagulant.

After one year if the patient has no further coronary events it is reasonable to discontinue anti platelet

and to continue anticoagulant.

166 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

With per cutaneous coronary intervention long term anti platelet therapy needed to prevent stent

thrombosis but some may also require anti coagulation.

In patients with stable coronary syndrome a combination of Rivaroxaban and aspirin ,and aspirin

alone was tried. The incidence of the primary outcome (composite of cardiovascular death, stroke, MI) was

lower with Rivaroxaban plus aspirin when compared with aspirin alone but with more major bleeding

events.

Recent trials have explored the use of oral anti coagulation in patients with coronary artery disease.

while there is expanding role for oral anticoagulants with or without antiplatelet drugs, the bleeding is

significant, Treatment must be tailored after careful consideration of harm versus benefit.

Integrated Care of the Older People (ICOPE) -

Old Wine in a New Bottle?

A B Dey1, Dr Abhijith Rao2, Mamta Saini2

1Professor and Head, 2Senior Residents, Department of Geriatric Medicine, Ail India Institute of Medical Sciences, New Delhi

Comprehensive Geriatric Assessment (CGA) has been considered to be the basis of practice of

geriatric medicine for the last seventy years. Substantial research has been carried out to document its

utility in clinical practice. CGA remains descriptive and is a combination of tools to assess functional status

in older patients. It is time consuming, does not alter clinical outcome in very well preserved or very sick

patients and is neither expressed in numbers or grades like most other assessments. There is no biological

basis for CGA.

In last two decades the concept of intrinsic capacity as a measure of functionality has gained

acceptance in published literature. In 2015, World Health Organization (WHO) adopted intrinsic capacity

as a tool for assessment of older persons and proposed Integrated Care of Older People (ICOPE) to be

integrated in primary health care for screening, assessment and management of older individuals. ICOPE

is s step wise process comprising of five steps: Step 1: Screening; Step 2: Person-centred assessment; Step

3: Develop a personalized care plan; Step 4: Ensure referral pathway and monitoring of care plan; and Step

5: Engage communities and support caregivers. The final document after several rounds of discussion and

review was released on first October 2019. Screening involves assessment of loss or impairment in intrinsic

capacity in the domains of cognition, locomotor capacity, vitality, visual capacity, hearing capacity and

psychological capacity; and social care and support; and care giver support. In addition it is proposed that

medication review for polypharmacy and presence of co-morbidity such as diabetes mellitus, hypertension,

cerebro-vascular disease, cardiovascular disease, hypothyroidism and anaemia, need also be screened at

this stage. In Steps 2 and 3 person-centred assessment and personalized care planning is carried out,

followed by a decision on referral pathway and monitoring of care plan in Step 4. The Step 5 is about care

giving, social support and care giver burden. Screening these domains takes less than five minutes, which

makes it an excellent tool to be used both, in the community, as well as in an outpatient setting, and can

also be extended to a busy inpatient service as well.

ICOPE and CGA essentially aim to provide a comprehensive assessment of a senior citizen. While

CGA is an established process, ICOPE is still evolving. It provides a similar degree of assessment at

shorter time and additionally tries to influence management, referral and care-giving. Thus one can

conclude that ICOPE is CGA in a new package of improved time and care management. WHO considers

ICOPE as a framework which needs to be adapted to health system functioning and socio-cultural

compatibility. Considering the volume of care to be delivered in our health system, it is time to look at

ICOPE as an alternative in India.

Guest Lectures 167

Suicides in the Elderly- Is it an Area of Concern

Anju Kuruvilla

Professor, Department of Psychiatry – Unit I, CMC Vellore

Suicide rates have been reported to be higher among older people in comparison with other age

groups in several parts of the world, and thus constitute a major public health issue in many countries.

Specific health conditions and stress factors increase the complexity and multi-factorial nature of suicidal

behaviour in older adults. Factors that contribute to suicidal risk include social and economic factors,

psychiatric illness and physical illness. Interventions include individual and general population

approaches that incorporate medical as well as social and economic strategies.

Experimental Therapies in Management of Alzheimer’s Disease

Goel Ashish, Vaingankar Abhishek

Department of Medicine, University College of Medical Sciences, New Delhi

Alzheimer’s disease (AD) that had been shown to affect nearly 3.5% older Chinese

individuals in early 1990s has now been reported at 5.9% in Portugal in 2015. It has been

projected that there will be as many as 13.2 million individuals with AD in the United States

alone by the year 2050. It is popularly believed that the looming epidemic of dementia and

related disorders has been largely underestimated and the healthcare systems across the world

are unprepared to address the problem. While sophisticated imaging systems with the

incorporation of artificial intelligence are able to accurately predict dementia nearly 6-8 years

before onset of symptoms, treatment options remain limited and ineffective. The present work

systematically reviews therapeutic randomized control trials on AD that have been published in

the last five years. The review classifies and discusses AD therapies as a) pharmaceutical agents

not regularly used for this indication (such as liraglutide, nilvadipine etc); b) biologicals and

antibodies (such as crenezumab, solanezumab); c) procedures (such as acupuncture, plasma

exchange); d) dietary modifications and food supplements (such as coconut oil, antioxidants) and

e) miscellaneous (multi-domain cognitive training, creative expression therapy)

168 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

Subjective Cognitive Impairment: A Harbinger of Dementia?

S.R. Chandra

Neurophysician, Ramachandra Charitable Hospital, Trivandrum

Introduction : Subjective cognitive decline initiative working group is an established international

consortium to create research criteria for evaluation of persons with SCD. There are different synonyms

SCI (Subjective cognitive impairment) or SCC (Subjective cognitive complaint).

The term means everyday cognitive concerns raised by persons without objective evidence of

dementia). They are etiologically heterogenous and irrespective of the nature of the disease, the quality of

life is affected there is an increase in mortality reported in some studies. This entity is considered as a

probable earliest sign of dementia. Decline is defined as a change to MCI or dementia over time. Which

mental process impairment, biomarker, functional neuroanatomy causes this? Numerous papers are

published and their heterogeneity is due to the lack of understanding on mode of administration, number

of terms, response options, domains to be tested etc in neuropsychological testing. The suspicion of this

entity being a pre MCI is based on reports that Aβ deposition correlates with SCD but not objective

cognitive impairment. Amyloid status however predicts future decline. Tau is associated with SCD ,

cortical volume ,medial temporal atrophy, white matter changes and indicates decreased structural

integrity in the memory system. Reisberg in 1985 using Global Deterioration Scale predicted SCD above

grade 2 is not normal, and grade 3 MCI, 4 and more dementia. SCD has more depression, according to

Bolla et al, and depression influences hippocampal volume. Gurvits et al suggested a complex interaction

between these three states. The outcome studies are limited in their interpretations as early dementias

and MCI were excluded. Geerlings reported a three times increased risk in 3.5 years. John and

Montgomery, as well as Wang et al said that this risk does not exist. Cognitive tests are difficult to

quantify between SCD and non SCD. Biological assessment with EEG showed increased theta. Voxel based

morphometric studies reported grey matter differences in medial temporal, frontal and other neocortices. A

smaller hippocampus was reported by Vanden filler. PET studies report decreased cerebral metabolism of

glucose in parietal temporal and para hippocampal regions. Those who had SCD with Apoe 4 allele had

more alterations in these tests than those who are negative. Higher cortisol was reported by Wolf et al. F-

MRI studies have revealed no change in performance during tasks, but observed differences in functional

brain activation. When semantically related words were used, increased activation of lateral prefrontal

cortex was seen and led to the “compensatory theory” calling it a compensation for decay of hippocampal

memory system elsewhere. Testing of episodic memory and valuation system revealed decreased

preference for future oriented tasks, attenuating attention and subjective evaluation system. The

phenomena of ‘Negative Subsequent ‘ is postulated to be the cause of increased activation for failed recall.

The differentiation theory says loss of specialization results in diffuse brain activation. But how this

hyperactivity contributes to SCD is not clear. Homeostasis breakdown theory says loss of comprehensive

temporal dynamics. The prediction error theory describes that brain functions as a statistical optimization

engine and makes implicit prediction of inputs actively making inferences instead of passively recording.

Predictive coding is the principle by which there is comparison of internally generated predictions and

external reality. Awareness of subtle errors can be in multiple domains causing SCD. Homeostasis

breakdown occurs and compensatory functions act for some time, but these can lead to glutamate excite-

toxicity and cell death. Depression is a common cause for SCD and there are probably complex interactions

between depression, SCD, MCI and dementia. Longer the follow up, the longer the conversion to MCI or

demntia. Is it time to separate SCD from MCI? MCI includes SCD as a core feature but how many normal

elderly have SCD ? Does it affect MCI prevention ? The Steel valley study revealed 6.3% persons without

SCD qualified for MCI where as only 3.2% from SCD group. CSHA (Canadian Study of Health and ageing)

evaluated how this adversely affects MCI. Relationship between subjective and objective cognitive

impairment is not straight forward and persons can be categorised as group 1 where both are

present,group 2 where neither is present, group 3 subjective alone, group 4 objective alone. The risk is

more if both are present. Accurate risk profiling did not happen in spite of ten years research. Both

subjective and objective tests are important. The use of other features with SCD increase the specificity

and positive predictive value and decrease the sensitivity and negative predictive values. In the absence of

any other clinically relevant features or association with other markers, the available data is doubtful

about the significance of SCD as a harbinger of dementia.

Guest Lectures 169

Vitamin K Antagonists vs NOAC – Do We Know Enough to Decide?

V. Srinivas1, Rajendran Magesh2

1. Consultant Geriatrician, Fortis Malar Hospitals, Chennai

2. Consultant Geriatrician, Apollo Hospitals, Chennai

Anti coagulants are an important class of drugs which are often life saving. These have been in

clinical use from 1950s. The clinical indications are very well defined. There have been several drawbacks

- mainly drug interactions and altered absorption with some food items. There was also the issue of

mandatory blood tests for monitoring the efficacy and safety of these drugs. Even in developed countries

getting INR in remote, inaccessible areas was impossible. Unfortunately, a lot depends on the INR. A high

value increases the risk of bleeding and a low value negates the benefit of using these drugs. However, the

greatest advantage of these drugs is that we have a huge body of experience and evidence of efficacy and

side effects.

In this scenario, introduction of Direct Oral Anticoagulants (DOAC) revolutionised anti coagulation in

the last ten years. These do not need any blood monitoring and also have fewer interactions. But the

challenge is, can they treat everything and replace warfarin? Ideally the perfect anticoagulant drug should

be effective, orally administered, with a fast onset of action. It should have predictable pharmacokinetics

with very few drug interactions compared to warfarin and have an effective antidote to tide over bleeding

episodes.

Dabigatran a factor IIa antagonist, Apixaban, rivoroxaban and endoxaban are factor Xa antagonists

are the new class of drugs classed as DOAC ( or NOAC ). Dabigatran is renally cleared (which raises

concern about its use in patients with moderate to severe chronic kidney disease) while the factor Xa

antagonists are minimally cleared by kidney. A meta-analysis (n=34,000 with 14,000 on DOAC) of patients

with Chronic Kidney Diseaes (CKD) taking DOACs concluded it was safe and suggested reduced risks of

stroke, systemic embolism, and death from any cause.

There is no significant difference in drug clearance in the elderly. There is concern about increased

risks of falls with resultant intracranial haemorrhage, which leads to reduced use of oral anticoagulant

(OAC) in elderly patients. In this group after carefully assessing the relative benefits and risks of

anticoagulation, DOACs can be used. There is a trend towards lower incidence of ICH with these newer

agents in the elderly.

In Venous Thromboembolism (VTE), data suggest that the decrease in VTE recurrence is seen with

prolonged periods of anticoagulation which is achieved at the expense of an increased risk of bleeding.

Thus, indefinite anticoagulation is most likely to benefit those with an increased risk of recurrence in

whom the risk of bleeding is low. DOACs have fewer drug interactions compared to warfarin. They do not

need monitoring of INR, which makes DOACs a favourable choice for longterm oral anticoagulation.

An important clinical issue is that in high risk elderly patients, there have been attempts to use long

term anti coagulation. In this scenario, cost of the drug becomes important. However, we are debating the

time tested and much more economical Vitamin K antagonists over the fairly recent and more expensive

DOACs. Do we favour experience over convenience? Do we choose ease of reversal in the case of overdose

with Vitamin K antagonists? Or do we continue a drug class without checking its efficacy, because there

are no ostensible side effects? We are attempting to answer these vital questions in our presentation, which

will impact our clinical practice.

170 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

“Merchants of Immortality” - Longevity Research

Naganath Narasimhan Prem

Chief Consultant Geriatric Medicine/Elder Care Specialist, Jaslok Hospital, Mumbai

The cluster of elderly population is on the rise. With better medical facilities and improved health,

they are living longer. The oldest old (>80 yrs) group is on the rise and we are also looking at more

centenarians. Longevity involves interacting mechanisms that may be genetic, environmental, cultural, or

geographic in origin. There is growing evidence that resiliency or the ability to adequately respond to or

resist various stressors, plays a key role in conferring successful aging. Several strategies can be employed

to positively influence health and life span, including dietary modification (eg, moderate caloric restriction)

to achieve and maintain ideal weight, exercise, healthy behaviours, avoidance of smoking and excessive

drinking, active engagement, and development of social networks and support systems. Putative

biomarkers of primary aging may also represent possible predictors of longevity.

Each measurement has its limitations as a reliable biomarker for aging and longevity. Some

biomarkers have relevance to both biological and functional aspects of exceptional longevity, including gait

speed and preservation of ability to perform ADLs. Other biomarkers are biochemical measurements used

in clinical practice that in combination have value in estimating biological age. Some are system-specific

measurements that are likely surrogates for overall health. Careful observations in the oldest old offer

empirical strategies that favour increased health and life spans, with implications for compression of

disability, identification and implementation of lifestyle behaviours that promote independence, and better

clinical decision making by assessment of biological age.

More research and evidence needs to be gathered for us to be ready for the holistic care of the ever

increasing longevity in the older population.

Key words : Longevity, successful ageing.

Rapidly Progressive Dementia in the Older Person -

An Evidence Based Approach

Dr. Ravi Bhat

1 Divisional Clinical Director and Consultant Old Age Psychiatrist, GV Area Mental Health Service,

Shepparton, Victoria, Australia 2Associate Professor of Psychiatry, Department of Rural Health, The University of Melbourne,

Shepparton, Victoria, Australia

Rapidly progressive dementias (RPD) are rare. Rare diseases are defined as those that affect less 1 in

2000 people. While there is no agreed upon definition of RPD, four retrospective studies from tertiary

centres have used deterioration in cognition within twelve months as a criterion for RPD. Any

investigation should consider known base rates of various RPD in the setting where the patient presents.

Early occurrence of neurological signs and symptoms, fever/meningeal signs help to heighten the suspicion

of the possibility of non-neurodegenerative causes of RPD. About a quarter of RPD may be treatable.

Hence, rapid decline and potential for treatment and/or reversal demand intensive work up and

management. The presentation will discuss the important aetiologies for RPD and approach to diagnosis.

Guest Lectures 171

Frailty: Disease Burden and Screening

Visvanathan R1,2

1National Health and Medical Research Council, Centre of Research Excellence in Frailty and Healthy Ageing,

Australia 2Adelaide Geriatrics Training and Research with Aged Care (GTRAC) Centre,

Faculty of Medicine and Healthy Sciences, University of Adelaide, South Australia

Frailty is an increasing health problem globally and in Australia, it is projected to affect 600,000

older Australians by 2027, with another 1.39 million at risk. Frailty is more prevalent in older age and

given that the fastest growing age demographic is that age 85 years and older, then frailty will be

encountered by our health systems more frequently.

Frailty is a burden for the sufferer, their family and when poorly managed costly to the health

system. The condition usually results in recurrent falls and injuries, along with frequent clinic and hospital

visits and progressively leads to decline, both physically and psychosocially, and increased reliance on aged

care services sooner than would otherwise be expected.

Frailty is a dynamic state and a downward decline in health is not the only trajectory, as

improvement in frailty status is possible. Unfortunately, the emergence of frailty is often unrecognised and

goes untreated, when the condition could be stabilised or even reversed. Clinicians may believe that they

would recognise frailty when they see it, but this is far from reality.

Systematic screening for frailty allows for earlier identification of the risk and when coupled with an

assessment and management plan that is person-centred, it offers the best chance for the older person to

improve, if not remain stable. Whilst population screening is currently not recommended, strategic case

finding within primary care may be an approach worth considering and several screening tools for frailty

exist.

The current approach to care is at most times hospital-centric, reactive and episodic, and not

necessarily in the best interest for the frail older person. A systematic and proactive approach to frailty,

based in the community through primary care, should be considered as an important part of our health

system.

Novel Biomarkers for Sarcopenia and Frailty in Old Age

Sharmista Dey

Associate Professor, Department of Biophysics, AIIMS, New Delhi

Introduction: The population of older people is increasing rapidly, but the percentage of successful

healthy in the old is very low. Due to lack of physical and social engagement, the older people gradually

develop sarcopenia and finally become frail. Sarcopenia is the degenerative loss of skeletal muscle mass

(0.5–1% loss per year after the age of 50), quality, and strength associated with aging. Sarcopenia is a

component of the frailty syndrome. Muscle degeneration in the lower organism was observed due to loss of

anti-oxidant protein. The cross sectional study was performed to assess the level of novel anti-oxidant

proteins in frail and non-frail older subjects with an objective of highlighting it as a marker of frailty in old

age.

Methods: Serum Sestrins (Sesn 1 and 2) and Sirtuins (SIRT1-7) were estimated by Surface Plasmon

Resonance (SPR) and Western Blot in non-frail and frail individuals. Receiver operating characteristic

(ROC) and multivariable regression analysis were done with different co-morbidities.

Result: The significant difference in serum sirtuins and sestrins level was observed between frail

and non-frail elderly.

172 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

Nutrition in the Elderly

Sumathi Swaminathan

Associate Professor, Department of Nutrition, St John’s Medical College and Research Institute, Bengaluru

Ageing is a natural process associated with physiological changes. Lifestyle changes, environment

and diet further impact health of the elderly. Nutrient requirements for the elderly remain the same as an

adult population, although depending on several factors, certain adaptations in diet may be required.

Despite challenges due to ageing, ensuring a nutrient dense diet with adequate physical activity is

essential for maintenance of optimal health and healthy ageing.

Interpreting DXA and FRAX Scores

Swapna Alexander

Consultant Orthogeriatrician, North Wales

Prevention of osteoporosis and its associated fractures is considered essential to the maintenance of

health and quality of life.

DXA scanning is used widely in the diagnosis of osteoporosis. Bone mineral density (BMD)

measurement by DXA (Dual energy Xray Absorptiometry) is used to diagnose and monitor osteoporosis.

However when patients are at intermediate risk (ie osteopenia) there is a need to quantitate the risk of

fractures, with a view to consider treatment in high risk individuals.

The most widely used fracture prediction instrument is the WHO risk assessment tool FRAX. This is

a widely used algorithm for fracture risk assessment.

FRAX along with BMD predict 10 year fracture probability much more accurately than BMD or

clinical risk factors alone in both men and women >50 years of age. Concurrent use of DXA scanning and

FRAX scoring improves fracture prediction and the selection of the most appropriate individuals for

treatment.

The use of DXA and FRAX and their individual uses and limitations will be discussed using case

vignettes.

Guest Lectures 173

Prevention of Delirium in Hospitalised Elderly Patients

G.S. Shanthi

MD, Head, Dept of Geriatrics, Madras Medical College, Chennai

Delirium is a serious disturbance in mental abilities that results in confused thinking and reduced

awareness of the environment. The start of delirium is usually rapid — within hours or a few days. The

duration is variable and the degree of severity ranges from mild to very severe and characterized by

disturbance of attention, with additional disturbance in cognition, not attributable to any pre existing

disease and fluctuates during the course of the day. It can be hypoactive, hyperactive or mixed type.

Cognitive deficits constitute an important risk factor for delirium and may result in worse post

delirium deficits. In a systematic review, it is found that delirium in persons with dementia is associated

with more hospital readmissions and higher rates of institutionalization and mortality. Prevalence of

delirium in demented patients ranges between 22% and 89%. Hence it is important to prevent delirium in

elderly sick patients and especially in patients with pre-existing dementia.

Prevention of delirium: Non pharmacological interventions: According to many studies, they are

found to be useful in preventing delirium. There is benefit in applying the non-pharmacological methods to

prevent delirium, when compared with standard management. They are:

• Education: the observers conducted brief interviews with each patient's family members, in which

the main aspects regarding the clinical features and prognostic implications of acute confusional

syndromes were explained and accompanied by a specially designed pamphlet.

• Provision of a clock (analogue or digital as required by the patient) and calendar in the room.

• Avoidance of sensory deprivation (glasses, denture and hearing aids must be provided, as per the

individual’s requirements).

• Presence of familiar objects in the room (photographs, cushions and radio).

• Reorientation of patient provided by family members (current date and time, recent events etc.).

• Extended visitation times in old age homes (at least five hours daily).

Multicomponent nonpharmacological interventions to prevent delirium are effective in reducing the

incidence of delirium, decreasing length of hospital stay and avoiding institutionalization.

Proactive geriatric consultations may play an important role in the acute hospital management,

which reduced the delirium. These include

1. Adequate CNS oxygen delivery: supplemental oxygen to keep adequate saturation, medication

to raise the systolic blood pressure >2/3 baseline or >90 mmHg, transfusion to keep hematocrit

>30%.

2. Fluid/electrolyte balance: Treatment to restore serum sodium, potassium, glucose to normal

limits, treat fluid overload or dehydration detected by examination or laboratory investigations.

3. Treatment of severe pain with appropriate medications / therapy

4. Elimination of unnecessary medications:

5. Regulation of bowel/bladder function:

6. Adequate nutritional intake: Dentures used properly, proper positioning for meals,

Supplements, if unable to take food orally, feed via temporary naso-gastric tube

7. Early mobilization and rehabilitation

8. Prevention, early detection, and treatment of major postoperative complications like myocardial

infarction/ischemia, arrhythmia, pneumonia/chronic obstructive pulmonary disease, pulmonary

embolus and screening for and treatment of urinary tract infection

9. Appropriate environmental stimuli with use of glasses and hearing aids, provision of clock and

calendar etc.

10. Treatment of agitated delirium following an appropriate diagnostic workup. Reassurance and

the presence of the family can decrease these episodes.

174 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

Pharmacological intervention: Several studies on Intensive Care Unit patients reported a

significant reduction in delirium incidence favoring the pharmacologic agent. There is some evidence that

haloperidol, newer neuroleptics (e.g., risperidone or olanzapine) and melatonin may be effective in

reducing the incidence of postoperative delirium.

The presence of multiple co morbidities and predisposing factors like cognitive, functional or sensory

impairments are associated with a high incidence of delirium. Appropriate measures to prevent delirium

should be instituted.

Live Stronger for Longer – Falls and Fragility Fracture Prevention

in New Zealand Older People

Shankar Sankaran

Clinical Leader, Whole of Systems, Health of Older People and Consultant Geriatrician, New Zealand

New Zealand’s health system is facing an increasing demand for acute treatment and long-term

rehabilitation services as a result of an ageing population. Falls are the most common and costly cause of

injury in people over sixty five years old and are a significant contributing factor to health service demand.

The challenge is 99% of older person’s falls occur in the community setting where a targeted population

focus is required.

New Zealand has a national initiative Live Stronger for Longer, where central agencies (Ministry of

Health, Accident Compensation Corporation and Health Quality and Safety Commission) are partnering

with local health systems to better support and enable a nation-wide approach to improve falls and

fracture service outcomes for older people. Focussing on population based interventions that have proven

effectiveness in the community setting and integrated of falls and fracture prevention management, the

programme is supported by a national outcomes and best practice framework including key enablers such

as the Hip Fracture Registry, Fracture liaison Services, Guidelines and Clinical Standards. This initiative

has ambitious goals to support older people to live well and independently in their own homes and

emphasises the importance of building a network of clinicians focussed on agreed outcomes aligned with

priorities for older people.

The underlying problem is complex as falls in an older age group reflect frailty. No single funding

agency can achieve an integrated service delivery model that delivers consistent and reliable outcomes to

older people; a partnership approach across the sector, based upon an alliance model is critical.

The presentation will expand on the Whole of Systems approach on this important issue for frail older

people in New Zealand, including standards for hip fracture care empowered by the Australia and New

Zealand Hip Fracture Registry, Fracture Liaison Services focussing on secondary fragility fracture

prevention and Strength and Balance Exercise programme provision for community dwelling older people.

Guest Lectures 175

Newer Drugs for Osteoporosis

Thangam, D.

Senior Asst Professor, Madras Medical College, Chennai

Osteoporosis is a “disease characterized by low bone mass and microarchitectural deterioration of

bone tissue leading to enhanced bone fragility and a consequent increase in fracture incidence.”

Osteoporosis may also be defined either by the presence of a fragility fracture or by bone mineral density

(BMD) measurement. It may become evident only after a fracture. Osteoporosis-related fractures can

increase pain, disability, dependency, total health care costs, and mortality. Therefore Osteoporosis is also

perceived as a silent epidemic.

Bone is not simply a mineralized structure but a complex system of cell-cell, cell-matrix, and cell-

hormone interactions influenced by genetic background, lifestyle, and diet. Throughout life, bones are

remodeled, meaning that they are continuously resorbed by osteoclasts and replaced with new bone made

by osteoblasts. This process allows for maintenance of mechanical strength and repair. An imbalance in

remodeling activity in which resorption exceeds formation may result in the pathophysiological changes

seen in osteoporosis. Hormones and growth factors have a role in regulating bone function. Estrogen and

testosterone have a significant effect on bone remodeling primarily by inhibiting bone breakdown.

Cytokines that influence remodeling have also been identified, such as receptor activator of the nuclear

factor kappa-B ligand (RANKL). RANKL is produced by osteoblasts that bind to RANK receptors on

osteoclasts, leading to the activation and maturation of osteoclasts and culminating in bone resorption.

Recent advances in molecular bone biology have identified a potent protease named cathepsin K (CatK).

CatK is secreted by activated osteoclasts during the bone resorption process, resulting in the degradation

of bone matrix and breakdown of mineral components of bone tissue. Osteocytes have direct

communication with surface osteoblasts through molecules known as connexins. Two of those connexins,

sclerostin and DKK1, are strong inhibitors of osteoblast differentiation and function and play an important

role in the activation and regulation of bone in response to physiologic and mechanical stimuli.

Pharmacologic agents for the treatment of osteoporosis consist of antiresorptives and anabolic agents.

Antiresorptive medications primarily decrease the rate of bone resorption while anabolic medications

increase bone formation more than bone resorption. The main antiresorptive medications are

bisphosphonates, selective estrogen receptor modulators, calcitonin and denosumab. Currently only one

anabolic agent (teriparatide) is widely used for osteoporosis treatment.

A better understanding of the micro architectural physiology of bone has lead to the development of

newer drugs for the treatment of osteoporosis. Few of them are already approved for use in humans.

Others are still in various phases of clinical trials. They are generally used for those with very high risk for

fractures and in whom the regular first line medications cannot be used due to various reasons.

PTH analogue- Abaloparatide: Abaloparatide -the second recombinant human PTH (1–34)

analogue to reach the market,

It is indicated for the treatment of post menopausal osteoporosis in women at high risk for fracture,

defined as a history of osteoporotic fracture or multiple risk factors for fracture in patients who have failed

or are intolerant to other therapy for osteoporosis. It is available as an injection. The recommended, dose

is 80 mcg subcutaneously once daily into the periumbilical region of the abdomen.

Abaloparatide should be avoided in patients with Paget’s disease of bone, unexplained alkaline

phosphatase elevations, prior skeletal radiotherapy, primary or metastatic bone malignancy, or

hypercalcemic disorders, such as primary hyperparathyroidism.

The duration of therapy is limited to two years. Osteosarcoma was noticed in rats following a two

year use. It carries a risk of orthostatic hypotension, hypercalcemia, and urolithiasis. The most common

adverse reactions seen with the use of this drug in clinical trials were dizziness, nausea, head- ache,

palpitations, fatigue, upper abdominal pain, and vertigo.

It is to be avoided in those with pre-existing hypercalcemia and those with underlying hypercalcemic

disorders, such as primary hyperparathyroidism.

176 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

Sclerostin Inhibitors- Romosozumab, Blosozumab, Setrusumab: Romosozumab is a

humanized mono- clonal antibody that inhibits sclerostin. It is an anabolic agent. Administered in the dose

of 210 mg subcutaneously/month for twelve months. Adequate supplementation of the patient with calcium

and vitamin D during treatment is essential, otherwise it can result in hypocalcemia. A higher rate of

major adverse cardiac events (MACE), a composite endpoint of cardiovascular death, nonfatal myocardial

infarction, and nonfatal stroke was observed in a randomized controlled trial in postmenopausal women

treated with romosozumab, when compared with alendronate. Hypersensitivity reactions were also

reported. Other antisclerostin monoclonal antibodies being developed and tested include blosozumab and

BPS804 ( setrusumab). In phase II studies, Blosozumab usage in post menopausal women showed

encouraging results.

Cathepsin K inhibitors – Odanacatib, ONO-5334: Several cathepsin K inhibitors have been

evaluated, but so far only odanacatib and ONO-5334 have showed adequate efficacy and safety.

Odanacatib (ODN) is a selective cathepsin K inhibitor characterized by long half-life and oral

availability. It concentrates in the resorption lacunae where it prevents the binding of cathepsin K to its

substrates and, unlike bisphosphonates, it does not affect osteoclast formation and survival. It is given as

weekly dose of 50 mg for 2 years. Clinical trials involving postmenopausal women showed beneficial effects

on bone mineral density (BMD) and fracture prevention. ONO-5334 is an oral synthetic low molecular

weight inhibitor of cathepsin K. A phase II trial with ONO-5334 at different dosing regimens (50 mg twice

daily, 100 mg once daily, or 300 mg once daily) demonstrated significant increases in BMD at lumbar

spine, total hip (except 100 mg once daily), and femoral neck, as compared with placebo.

DKK1 inhibitor: DKK1 is another modulator of the Wnt signaling pathway which leads to

suppression and decreased bone formation. Monoclonal antibodies against DKK1 have been shown to

accelerate bone formation and increase BMD in animal models.

Src kinase Inhibitor-Saracatinib: Src tyrosine kinase is an enzyme with multiple regulatory

functions and is expressed at high levels in osteoclasts. It contributes to their survival and seems to be

essential for osteoclastic bone resorption. Saracatinib (AZD0530) is an orally available ATP competitive

inhibitor of Src kinase and in vitro has shown significant antiresorptive effects.

Guest Lectures 177

Stroke Thrombolysis in Elderly – Is it safe?

Senthil Raghunathan

MD FRCP (Glas),Consultant Stroke Physician,Nottingham City Hospital,Nottingham, United Kingdom

Background

Intravenous alteplase (recombinant tissue plasminogen activator) is approved for the treatment of

acute ischaemic stroke. Previous analyses of pooled data from randomised trials concluded that alteplase is

beneficial when administered to some patients within 4·5 hours, but that the magnitude of benefit

diminishes with increasing treatment delay.

However, uncertainties remain about the balance of benefit and risk when alteplase is given later to

older patients, or to patients with very severe or mild strokes. Present guidance from Europe and

elsewhere recommends the routine use of alteplase within 4·5 hours of stroke onset but, in the USA, the

Food and Drug Administration has approved the use of alteplase only within 3 hours of stroke onset.

Marketing authorisation for Europe and Australia, but not for the USA or Japan, cautions against

the use of alteplase for severe and mild stroke. Marketing of alteplase in some European countries is also

restricted to patients younger than eighty years (despite clinical guidelines based on observational studies

that recommend its use in older patients), whereas no such age restriction applies in many countries,

including the USA.

IST-3 (International Stroke Trial) —designed to resolve some of these uncertainties—included 3035

patients randomly assigned to alteplase or control up to 6 hours after the onset of stroke. The principal

investigators from IST-3 and other trials of alteplase agreed to make their individual-patient data

available for analysis. The chief goal of this analysis was to explore the extent to which treatment delay

affected the effect of alteplase and to establish whether age or stroke severity affected treatment effects.

These analyses assessing potential effect modification are only possible with individual patient data. Key

secondary aims included estimating the effect of alteplase on symptomatic intracranial haemorrhage and

on 90-day mortality.

Extrapolation of data from Stroke trial so far

This data provides further evidence about the extent to which treatment delay alters the beneficial

effect of alteplase for acute ischaemic stroke. We provide clear evidence for improved odds of a good stroke

outcome when treatment is started within 4·5 hours of ischaemic stroke, with earlier treatment resulting

in bigger proportional and absolute benefits. The average benefit of alteplase might even extend beyond 4·5

hours for some patients. The proportional benefits were similar for patients aged older than eighty years

compared with younger patients, and for patients with minor or severe strokes compared with other

patients.

This average expected benefit from giving alteplase within 4·5 hours occurred in spite of an average

absolute increase in the early risk of fatal intracranial haemorrhage (around 2%). Since alteplase had no

significant effect on early causes of death, or late(ninety days) causes of death, this 2% excess remained,

but was no longer statistically significant. Longer-term follow-up data are needed to test whether the effect

of alteplase on patients who survive the first week after their stroke have reduced long-term risk of death.

Contrary to analyses of individual patient data done before IST-3, the trend towards a bigger relative risk

of 90-day mortality with increasing treatment delay was not statistically significant.

However, if improvements in stroke outcome among survivors do lead to parallel improvements in

mortality, then one would expect that long-term survival will be greatest among those treated earliest (ie,

the group most likely to benefit from alteplase).

Our results support guidelines that recommend use of alteplase irrespective of age and up to 4·5

hours after onset of stroke.

178 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

In the USA, marketing authorisation has not been granted for use of alteplase after 3·0 hours, while

in some European countries marketing authorisation limits the use of alteplase to patients aged eighty

years or younger. In the present analysis, the lower limit of the 95% CI for the time at which the

proportional benefit on mRS 0–1 crossed the line of no effect was 5·0 hours, with statistically significant

evidence of benefit in the prespecified subset of patients with treatment delay after 3·0 hours, up to 4·5

hours. In addition, we found no evidence that age modified either the proportional benefits or the

proportional hazards of alteplase, with clear evidence of overall benefit for mRS 0–1 among the 1729

patients aged older than eighty years at randomisation. Nor was there evidence that older age shortened

the period during which such benefits were seen, according to a recent report.

The availability of individual data for a large number of patients enabled us to make a more precise

assessments of the relative effects of alteplase than has been possible previously. We also included more

than 1700 patients aged older than eighty years. The number of older patients with stroke is increasing as

a proportion of the general population and as a proportion of those with stroke, so our analyses provide a

reliable assessment of the effects of alteplase in this group by including patients from IST-3, which almost

doubles the number of patients available. They also differ from previous tabular meta-analyses through

the use of individual data, which enables direct assessment of the potential for effect modification. Our

prespecified analysis plan safeguarded against the potentially inappropriate combination of data from IST-

3 with those from the previous studies. In fact, the results from IST-3 were consistent with earlier trials

after adjustment for the main differences in patient characteristics.

Nonetheless, the open design of IST-3 and its broader definition of significant bleeding might have

inflated our estimate of the risk of parenchymal type 2 symptomatic haemorrhage. However, the number of

such events associated with early neurological deterioration or death was small, limiting the potential for

this to be a source of major bias. Furthermore, the overall results from IST-3 for symptomatic intracranial

haemorrhage were similar to those estimated from previous trials. Patients in IST-3 were also older on

average than patients in the eight previous trials. However, this difference provides one of the main

strengths of our analysis—the ability to compare the effect of alteplase reliably in old and young patients.

Although unknown systematic differences might also have existed between patients in IST-3 and patients

in the other trials, any such characteristics would have to be strong determinants of treatment effect

(rather than just predictors of risk) to produce material bias in our overall results.

Future work will investigate the potential independent effect on treatment effect of a range of other

characteristics, including sex, blood pressure, and baseline imaging features.

Conclusion

In conclusion, despite early increases in fatal intracranial haemorrhage, alteplase significantly

improves the overall likelihood of a good stroke outcome at 3–6 months. The proportional benefit increases

with earlier treatment and remains statistically significant up to at least 4·5 hours after initial stroke

symptoms, irrespective of age or stroke severity.

Guest Lectures 179

Choice of Insulin Therapy in Elderly

Usha G.

Professor of Geriatrics, Madras Medical College, Chennai

Introduction: Diabetes is an important health condition for the aging population. Approximately

one quarter of people over the age of sixty five years have diabetes and this proportion is expected to

increase rapidly in the coming decades.

Diabetes in elderly: Diabetes has been considered to be a part of the premature aging syndrome, as

age related diseases such as cardiovascular disease, cancer, cognitive changes and dementia occur

prematurely in people with diabetes.

Diabetes in the elderly may present in two forms:

• Diabetes of long duration

• Senile diabetes appearing above the age of sixty five years

Aging is commonly associated with deterioration of the insulin secreting capacity and this reduced

insulin activity resulting in senile diabetes.

Older people with diabetes have higher rates of functional disability, chronic diseases, ill health and

are at risk of developing geriatric syndromes. Age related changes in functional ability and senses will

affect patient’s ability to administer insulin, monitor blood glucose and manage hypoglycemia. Social

isolation is another factor leading to more dependency in caregivers. Therefore the approach to insulin

therapy in older patients with diabetes requires special consideration

Insulin: The general principle of insulin use is to achieve a normal glycemic profile,without

significant side effects. Long term goals are to prevent or slowdown the development of microvascular and

macrovascular complications of diabetes. In elderly, persistent hyperglycemia should be avoided to prevent

the development of a hypercatabolic state which leads to muscular wasting or sarcopenia and frailty.

Minimizing hyperglycemia is also important for maintaining cognitive function.

Indications for insulin in elderly include persistent symptomatic hyperglycemia despite non

insulin therapy. Hyperglycemic complications include increased confusion, dehydration, and infections.

Ketosis, ketonuria, weight loss, pancreatitis, hepatic cirrhosis, renal failure, cardiac failure , chronic

inflammatory diseases, antirejection therapy, acute medical illness with acute decompensation are some of

the conditions where insulin is used.

Points to be considered before initiating insulin therapy

(1) Hypoglycemic unawareness is more common in elderly with increased cardiovascular risk hence

glycemic target level have to altered based on health and functional status

(2) Multiple medical co-morbidities are more common in the elderly, hence insulin initiation and

dose needs to be titrated accordingly

(3) In patients with long term complications like diabetic nephropathy, peripheral neuropathy,

coronary artery disease, peripheral vascular disease, diabetic gastroparesis insulin regimen

have to be carefully tailored.

(4) The patient’s cognition and mood, ability to administer insulin, ability to recognize and treat

hypoglycemia, ability to monitor blood glucose, availability of care givers and support at home

needs to be assessed prior to the initiation of insulin.

(5) The patient and the caregiver need to be counseled regarding the natural course of diabetes,

benefits of insulin, glycemic goals, hypoglycemic risks. etc

Common barriers to insulin therapy in elderly include, inability to self administer insulin due to

poor vision, impaired manual dexterity, poor physical function, impaired cognition. Other patient related

180 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

barriers like needlophobia, fear of weight gain, hypoglycemia, misconceptions about insulin like stigma and

religious beliefs exist.

Advantages of insulin therapy in elderly includes improves quality of life and well being, has

potential powerful anabolic effects – helps wound healing, prevents muscle wasting, delays development of

frailty and weight gain in frail patients.

Disadvantages of insulin therapy include frequent injection, frequent blood glucose monitoring,

weight gain in obese patients and risk of hypoglycemia.

Types of insulin: (1) Human insulin (2) Insulin analogs

INSULIN TIME TO ONSET OF

ACTION(hours)

PEAK ACTION

(hours)

DURATION OF

ACTION(hours)

HUMAN INSULIN

1.Rapid acting

Regular insulin 0.5-1 2-4 6-8

2.Intermediate acting

NPH insulin 2-4 5-7 14-24

Insulin lente 3-4 4-8 16-20

3.Long acting

Ultralente insulin 6-10 Unpredictable 20-24

INSULIN ANALOGS

1. Rapid acting

Insulin lispro 0.25 1.5 3-5

Insulin aspart 0.25 1.5 3-5

Insulin gluisine 0.25 1 2

2. Long acting

Insulin glargine 2-4 No peak 20-24

Detemir 2 No peak 6-24

Degludec 2 No peak >40

Human insulin regimens containing neutral protamine hagedorn (NPH) and regular insulin (RHI)

have been used for controlling hyperglycemia. These regimens have significant pharmacological limitations

like variable onset, suboptimal duration of action and delayed onset of action. Hence, insulin analogs were

developed to closely mimic the pharmacokinetic and pharmcodynamic profiles of endogenous insulin. So

the effect of insulin is more predictable and there is a consistent glycemic effect with a reduced risk of

hypoglycemia is observed with insulin analog. However, cost of therapy is an important barrier with

insulin analogs in developing countries

Insulin regimens: Insulin regimens are of three types – basal, basal bolus and premixed.

Basal is the first choice regimen given once daily at bed time. It is suitable in all elderly diabetic

patients. Advantage of basal regimen includes it is simple, once daily, easy titration, is associated with less

hypoglycemia and weight gain. It is less physiologic, with post prandial glucose excursions.

Basal bolus is preferred when basal regimen fails with persistent post prandial glucose excursions.

It is suitable in elderly with good physical and cognitive functions. Advantages include -it is more

physiologic, has good glycemic control, Disadvantages includes complex titration, frequent injections, high

risk of weight gain and hypoglycemia.

Premixed insulin regimen is preferred when basal regimen fails with persistent post prandial

excursions. It is suitable for well functioning patients and those with predictable eating pattern.

Advantages are simple administration, fixed dose and good glycemic control. Disadvantages include

inflexible titration, high risk of weight gain and hypoglycemia and this needs a regular eating pattern.

Guest Lectures 181

Treatment goals in elderly:

• Healthy (few co existing chronic illness, intact cognition and functional status) FBG 90 – 130

mg/dl, HbA1C < 7.5%.

• Complex/ intermediate (multiple co existing chronic illness or 2+ instrumental ADL impairments

or mild to moderate cognitive impairment) FBG 90 – 150 mg/dl, HbA1C < 8%.

• Very complex/ poor health (end stage chronic illness or moderate to severe cognitive impairment or

2+ ADL dependencies) FBG 100 – 180 mg/dl, HbA1C < 8.5%.

Insulin delivery: Newer insulin delivery devices like pen devices may help the patient to adapt to

insulin therapy faster and they have advantage over the conventional syringe and vial method of insulin

administration. The large digits on the dosing dial allow for more precise dosing. Newer devices with an

audible click provide an auditory aid to dose selection and administration. These devices are easy to use

and allow precise dosing even in elderly patients who may have limited manual dexterity.

Conclusion: Treatment goals of diabetic management in elderly should be individualized. Glycemic

goals and type of insulin regimen in elderly patients must be tailored to meet the need of individual

patient. Care in adults with functional limitation and limited life expectancy should focus on enhancing the

quality of life rather than to normalize the blood glucose level.

182 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

COPD - Improving Quality of Life in the Older Person

Y. Sathyanarayana Raju, Y. Rahul, Y. Sairam Reddy

Professor and Head, Department of General Medicine, Nizam’s Institute of Medical Sciences,

Panjagutta, Hyderabad 500482 Telangana

Introduction

The elderly population is increasing the world over. As per the estimates of the World Health

Organization (WHO), the proportion of the population aged over 60 years will double from 11% in 2002 to

22% by 2050 (1). By the year 2021, it is estimated that the proportion of over-sixty year population is

expected to increase to 10.7% in India (2,3).

Chronic obstructive pulmonary disease (COPD) is a global health problem (4,5) [1]. By 2020, COPD is

expected to cause 4–5 million deaths (7% of all deaths) globally annually. COPD in the elderly is

characterized by a high symptom burden and mandates intense healthcare utilization. Further, mortality

in COPD is higher due to the unmet needs of health caregivers and elderly subjects with COPD (6).

Epidemiology Of COPD In The Elderly

Methodological issues

Precise estimates of prevalence of COPD in elderly are not available due to use of imprecise definition

and measurement tools, because of which large variations have been noted in prevalence estimates.

However, even giving allowance for lack of precision in measuring the prevalence, COPD is considered to

be a serious health problem that has significant effects on healthcare services and the quality of life in of

elderly subjects.. In a systematic review on the global burden of COPD, the pooled prevalence of COPD in

individuals aged sixty five years or older was computed to be 14.2% [95% confidence intervals (CI) 11%-

18%] compared with 9.9% (8.2 to 11.8%) in those younger than forty years (7). The burden of COPD in the

elderly in India is expected to be similar.

Quality of life in COPD patients

COPD is a non-curable disease, which progressively reduces the breathing capacity and impairs

patients’ ability to carry out his or her activities of daily living, thereby adversely affecting health-related

quality of life (QOL). In a community-based cross-sectional study (8) from India assessing the QOL of

COPD patients (n=124) using a using a disease-specific questionnaire [SGRQ-C, a shorter version derived

from the original version St. George's respiratory questionnaire (SGRQ)], it was observed that QOL was

impaired across all three domains, namely, symptoms, activity, and impact in COPD patients. .

Challenges In Management Of COPD In Elderly

The management of elderly patients with COPD is extremely challenging. While COPD is a major

cause of breathlessness, exercise limitation and respiratory failure in the elderly, several other causes and

co-morbid conditions like malnutrition, de-conditioning, anxiety, congestive cardiac failure, pulmonary

embolism, drugs and medications may exacerbate the symptoms of COPD. Further, it has been observed

that almost one-third of the elderly COPD patients are unaware of the treatment options and control

measures for COPD (9). However, little attention has so far been paid to all the dimensions of

empowerment in the management of COPD in the elderly.

Guest Lectures 183

Improving Quality Of Life In Elderly Patients With COPD

Current data suggest a need to empower elderly COPD patients for better self-management,

Furthermore, behavioural modifications aimed at improving efficacy and quality of life, and reducing

disability and healthcare costs are also mandated. Such an empowerment is likely to enable elderly

patients with COPD to actively be involved with health care providers in planning and participating in

decision making regarding their treatment decisions (10-13).

It has been observed that meeting the many needs of elderly COPD patients and their

caretakers/families mandates that clinicians supplement guideline-recommended standardized care with

treatment decisions taking into account the co-morbid conditions, objectively evaluate the risk-benefit

trade-offs engendered by the increased risk of adverse events. Treatment decisions should also focus on

providing adequate symptom relief and restoring functionality, and preparing elderly patients and their

families for possible further decline in the patient’s health and planning for their end-of-life care (9-12).

Improving Quality Of Life In The Older Person With COPD

Several measures, such as, smoking abstinence, physical exercise/activity, consuming an

appropriately nutritious balanced diet, ensuring adequate sleep, keeping themselves active pursuing

hobbies/interests, prior planning/arranging help for adhering to complex treatment medication regimens

for COPD and co-morbid conditions can help in improving quality of life of elderly patients. Elderly

patients with COPD also need to be educated regarding recognising signs and symptoms of deterioration

(for e.g., worsening dyspnoea, change in colour, character, consistency and quantity of sputum) and

knowing what to do to prevent or reverse them; and importantly when to seek medical consultation (9-12).

A team approach by clinicians, nurses, paramedical staff, respiratory physiotherapists, clinical

psychologists, would go a long way in pulmonary rehabilitation and ensuring a good quality of life in

elderly patients with COPD.

Table 1: Measures for improving quality of life in older persons with COPD

Smoking abstinence

Physical exercise/activity

Consuming an appropriately nutritious balanced diet

Ensuring adequate sleep

Keeping themselves active pursuing hobbies/interests

Prior planning/arranging help for adhering to treatment

Annual vaccination (e.g., influenza vaccination)

Education regarding recognising signs and symptoms of deterioration and

preventive measures

Education regarding when to seek medical consultation

COPD = chronic obstructive pulmonary disease

References

1. World Health Organization. Facts about ageing. Avaiable at URL: http://www.who.int/ageing/about/facts/en/.

Accessed on October 10, 2019.

2. Population composition. Available at URL: http://www.censusindia.gov.in/vital_statistics/SRS_Report/

9Chap%202%20-%202011.pdf. Accessed on October 10, 2019.

3. Central Statistics Office Ministry of Statistics & Programme Implementation Government of India Situation

analysis of elderly in India., June 2011. Available at URL: http://mospi.nic.in/mospi_new/upload/elderly_

in_india.pdf. Accessed on October 10, 2019.

4. López-Campos JL, Tan W, Soriano JB. Global burden of COPD. Respirology 2016;21:14-23.

5. Celli BR, Wedzicha JA. Update on clinical aspects of chronic obstructive pulmonary disease. N Engl J Med 2019;

381:1257-66.

6. Vijayan VK. Chronic obstructive pulmonary disease. Indian J Med Res 2013;137:251-69.

184 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

7. Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino DM. Global burden of COPD: systematic

review and meta-analysis. Eur Respir J 2006;28:523-32.

8. Ahmed MS, Neyaz A, Aslami AN. Health-related quality of life of chronic obstructive pulmonary disease patients:

Results from a community based

9. cross-sectional study in Aligarh, Uttar Pradesh, India. Lung India 2016;33:148-53.

10. Robinson T. Empowering people to self-manage COPD with management plans and handheld records.Nursing

Times 2011; 106: 38. Available at URL: https://www.nursingtimes.net/clinical-archive/copd/empowering-people-to-

self-manage-copd-with-management-plans-and-hand-held-records-25-09-2010/. Accessed on October 10, 2019.

11. Fotoukian Z, Shahboulaghi FM, Khoshknab MF, Mohammadi E. Concept analysis of empowerment in old people

with chronic diseases using a hybrid model. Asian Nurs Res (Korean Soc Nurs Sci) 2014;8:118-27.

12. Fotokian Z, Mohammadi Shahboulaghi F, Fallahi-Khoshknab M, Pourhabib A. The empowerment of elderly

patients with chronic obstructive pulmonary disease:

13. Managing life with the disease. PLoS One 2017;12:e0174028.

14. Fried TR, Vaz Fragoso CA, Rabow MW. Caring for the older person with chronic obstructive pulmonary disease.

JAMA 2012; 308:1254-63.

15. Vanfleteren LEGW, Ullman A, Fabbri LM. Time for a longer and better life for patients with COPD. Eur Respir J

2018; 51(1).pii:1702569.

Guest Lectures 185

Diuretics in the Treatment of Hypertension in Elderly

Indrajeet Singh Gambhir1*, Chandra Shekhar Azad2

1Department of Geriatric Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India 2Department of General Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India

*Corresponding Author

Introduction:

Hypertension is a very common disorder, particularly past middle age. It is an important risk factor

for cardiovascular mortality and morbidity. Hypertension is defined as the level of blood pressure at or

above which long-term antihypertensive treatment is proven to reduce cardiovascular mortality. The Joint

National Committee 7* (2003) and WHO-Isolated Systolic Hypertension (2003) guidelines state that 140/80

mm Hg is the cut-off for hypertension, though the risk of complications appear to increase at levels above

120/80 mm Hg, therefore newer guidelines had to be constructed. [1-3] Epidemiological studies have

confirmed that higher the systolic or diastolic pressures, greater is the risk of cardiovascular disease.

Hypertension affects around 67% of elderly people [4]. An individual aged 55 to 65 years without

hypertension has a 90% lifetime risk of developing hypertension.

Elderly hypertension is peculiar in that diastolic pressure is stable or falls after the age of 55 years

while systolic pressure rises due to arteriosclerosis, resulting in wide pulse pressure, a condition termed

isolated systolic hypertension. Due to arteriosclerosis there may be pseudo hypertension. Orthostatic

hypertension is important to consider and all elderly should have their blood pressure recorded both in

supine and standing postures.

Trials on Elderly hypertension

The European Working Party on High Blood Pressure in the Elderly (EWPHE) analyzed

elderly antihypertensive treatment and demonstrated that the beneficial effects of treatment decrease with

advancing age, while in patients over the age of eighty years, little or no benefit could be demonstrated.

The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) randomized

1,627 patients of age between 70 years and 84 years to active treatment with a beta blocker and diuretic or

a placebo and reported a 73% reduction in fatal strokes, 38% reduction in non-fatal strokes, 40% reduction

in all cardiovascular events and a 43% reduction in all-cause mortality in the active treatment group. In

the 235 patients who were aged eighty years or more, there was no evidence of benefit for either stroke or

total mortality.

The Systolic Hypertension in the Elderly Program (SHEP) studied the effect of treatment in

people aged sixty years and above with isolated systolic hypertension. Patients given diuretic and/or a beta

blocker showed 36% reduction in all stroke events, 32% reduction in all cardiovascular events and 13%

reduction in death from all causes with respect to those given placebo. In patients aged over eighty years,

there was a 45% reduction in stroke events but no decrease in stroke death or total mortality.

The Systolic Hypertension in Europe (Syst-Eur) study investigated whether treatment with a

diuretic or any other drug (as necessary), could reduce the risk of cardiovascular complications in people

aged sixty years or more, isolated systolic hypertension. Active treatment reduced the incidence of strokes,

cardiac end points and cardiovascular end points. For both total and cardiovascular mortality, the benefits

of treatment weakened with age; in the 441 patients aged eighty years or more, mortality increased in the

treatment group.

These trials underline the effectiveness of treating hypertension and its benefits in reducing

morbidity and mortality in elderly up to 80 years of age. The Hyvet 1 trial (2008) failed to show mortality

benefits in those 80 years and above, but the Hyvet 2 trial (2018) with raised target systolic blood pressure

to 150 mm Hg showed immense benefits in morbidity as well as mortality.

186 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

Diuretics:

Diuretics have been standard antihypertensive drugs over the past four decades, though they do not

lower blood pressure in normotensives.

Classification

• Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide

• Loop diuretics (High ceiling): Furosemide, Torsemide

• K+ sparing: Spironolactone, Amiloride, Eplerenone

Loop Diuretics (High ceiling): These are used as diuretics only and not for the routine treatment

of hypertension. Furosemide is a strong diuretic, but the antihypertensive efficacy does not parallel its

diuretic potency. It is a weaker antihypertensive than thiazides; fall in BP is entirely dependent on

reduction in plasma volume. The natriuretic action lasts for only 4–6 hours from the conventional morning

dose. Loop diuretics are also more liable to cause fluid and electrolyte imbalance, weakness and other side

effects.

Potassium sparing diuretics: These are used only in conjunction with a thiazide diuretic to

prevent K+ loss and to augment the antihypertensive action of thiazides. Spironolactone is not favored

because of its hormonal side effects (gynecomastia, impotence, menstrual irregularities). To evade these

problems, a newer aldosterone antagonist eplerenone is being increasingly used. With the recent

appreciation of the role of aldosterone in promoting hypertension related ventricular and vascular

hypertrophy and renal fibrosis, it is surmised that aldosterone antagonists will attenuate these

complications. As such, there is resurgence in their use, especially in refractory hypertension. Potassium

levels should be monitored when K+ sparing diuretics are used with Angiotensin converting enzyme (ACE)

inhibitors/ Angiotensin receptor blockers.

Thiazides and Thiazides like diuretics:

Indapamide: It is a mild diuretic, chemically related to chlorthalidone and reduces blood presure at

doses which cause minimal diuresis. Electrolyte disturbances and K+ loss are minimal at antihypertensive

doses. It probably has additional vasodilator action exerted through alteration of ionic fluxes across

vascular smooth muscle cell. Indapamide is well absorbed orally, has an elimination t½ of 16 hrs. Single

daily dose (2.5 mg) is enough. It is well tolerated; side effects are minor gastrointestinal symptoms and

fatigue. Hypokalemia is infrequent.

Thiazides (hydrochlorothiazide, chlorthalidone): These are the diuretics of choice for uncomplicated

hypertension; have similar efficacy and are dose to dose equivalent. All major trials have been carried out

with these two drugs. Chlorthalidone is longer acting (~ 48 hours) than hydrochlorothiazide (< 24 hours)

and may have better round-the-clock action.

The proposed mechanism of antihypertensive action:

1. Initially, diuresis reduces plasma and extra-cellular fluid volume by 5–15%, and this decreases

cardiac output.

2. Subsequently, compensatory mechanisms operate to almost regain Na+ balance and plasma

volume; cardiac output (CO) is restored, but the fall in blood pressure is maintained by a slowly

developing reduction in total peripheral vascular resistance (TPR).

3. The reduction in TPR is most probably an indirect consequence of a small (~5%) persisting Na+

and volume deficit. Decrease in intracellular Na+ concentration in the vascular smooth muscle

may reduce stiffness of vessel wall, increase its compliance and dampen responsiveness to

constrictor stimuli (NA, Ang II). Similar effects are produced by salt restriction; and the

antihypertensive action of diuretics is lost when salt intake is high.

A mild slowly developing vasodilator action of thiazides due to opening of smooth muscle K+ ATP

channels and hyperpolarization has been proposed. The fall in blood pressure develops gradually over 2–4

weeks. During long-term treatment with thiazides, the heart rate and CO remain unaffected, while TPR is

Guest Lectures 187

reduced despite compensatory increase in plasma renin activity, which confirms persisting Na+ deficit.

Thiazides have no effect on capacitance vessels, sympathetic reflexes are not impaired: postural

hypotension is rare.

Thiazides are mild antihypertensives, average fall in mean arterial pressure is ~10 mm Hg. They are

effective by themselves in ~ 30% cases (mostly low grade hypertension) but they potentiate all other

antihypertensives (except DHPs) and prevent development of tolerance to these drugs by not allowing

expansion of plasma volume. Thus, in combination, they are useful in any grade of hypertension. They are

more effective in the elderly and maximal antihypertensive efficacy is reached at 25 mg/day dose, though

higher doses produce greater diuresis. Their antihypertensive action is attenuated by NSAIDs.

Desirable properties of thiazide diuretics as antihypertensives are:

1. Once a day dosing and flat dose-response curve permitting simple standardized regimens.

2. No fluid retention, no tolerance.

3. Low incidence of postural hypotension and relative freedom from side effects, especially

neurological, compared to sympatholytics.

4. Effective in isolated systolic hypertension (ISH).

5. Lessened risk of hip fracture in the elderly due to hypocalciuric action of thiazides.

6. Low cost.

Current status of diuretics as antihypertensives

The popularity of diuretics as antihypertensive has had ups and downs. In the 1960–70s they were

almost routinely prescribed alone or in combination, to nearly all hypertensive patients. The usual dose

used was hydrochlorothiazide/ chlorthalidone 50 mg/day. Soon several drawbacks were highlighted:

• Hypokalemia—muscle pain, fatigue and loss of energy

• Erectile dysfunction in males

• Carbohydrate intolerance: due to inhibition of insulin release (probably secondary to K+ depletion

which interferes with conversion of proinsulin to insulin); precipitation of diabetes.

• Dyslipidemia: rise in total and LDL cholesterol and triglycerides with lowering of HDL. This could

increase atherogenic risk, but no direct evidence has been obtained.

• Hyperuricemia: by inhibiting urate excretion— increased incidence of gout.

• Increased incidence of sudden cardiac death: attributed to episodes of torsades de pointes and

ischemic ventricular fibrillation precipitated by hypokalemia.

Over the past 25 years thiazides have been used at lower doses (12.5–25 mg/day hydrochlorothiazide

or equivalent) alone and in combination with a K+ sparing diuretic. The multiple risk factor intervention

trial (1982), the Medical research council trial (1987, 1992), the systolic hypertension in the elderly

programme (SHEP, 1991) and a case control study (1994) demonstrated that increased incidence of death

associated with thiazide use in the elderly was dose-dependent, and that 25 mg/day yielded the best

benefit-risk ratio. Favorable results obtained with ≤ 25 mg/day in the above and subsequent studies,

including ALLHAT (2002) and a meta-analysis (2003) have reinstated thiazide diuretics as the first choice

antihypertensives.

Complications of thiazide type diuretic therapy

1. Edema Thiazides may be used for mild to moderate cases. For mobilization of edema fluid more

efficacious diuretics are preferred, but thiazides may be considered for maintenance therapy.

They act best in cardiac edema; are less effective in hepatic or renal edema. Thiazides are

powerless in the presence of renal failure, but metolazone may still act. Cirrhosis patients often

develop refractoriness to thiazides due to development of secondary hyperaldosteronism.

2. Hypertension Thiazides and related diuretics, especially chlorthalidone are first line drugs.

188 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

3. Diabetes insipidus Thiazides decrease positive free water clearance and are the only drugs

effective in nephrogenic diabetes insipidus. However, they reduce urine volume in pituitary

origin cases as well.

4. Hypercalciuria with recurrent calcium stones in the kidney. Thiazides act by reducing Ca2+

excretion.

Hyponatremia:

Hyponatremia is a typical complication after thiazide diuretic treatment and is a potential cause of

morbidity and mortality. Loss-of-function mutations in the human renal outer medullary potassium

channel (ROMK) cause renal Na+ wasting. Older female patients with lower body mass indices and KCNJ1

rs2509585 C/T or T/T polymorphisms are more likely to develop thiazide-induced hyponatremia. The

combination of thiazide diuretics and either ACE-inhibitors or angiotensin II receptor antagonists are

associated with more hyponatremia [5].

Conclusion:

• Thiazides reduce cardiovascular endpoints in comparison to placebo in older people, particularly

regarding the risk of stroke.

• Thiazides are less effective than calcium channel blockers (ACCOMPLISH trial and NICE

guidelines) but SHELL study and ALLHAT study do not agree with the same.

• Thiazides were better than beta blockers (MRCO trial) for coronary event prevention.

• No study has compared thiazides with ACE inhibitors.

• Evidence is not enough for commencing thiazides for fracture prevention in older adult with

hypertension.

• Thiazides are listed on the STOPP list for patients with a history of gout (ACR Guidelines)

References

1. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention,

Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA. 2003;289(19):2560–2571.

2. World Health Organization, International Society of Hypertension Writing Group. 2003 World Health

Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J

Hypertens. 2003;21:1983-1992.

3. 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. J Am Coll Cardiol

2018;71:e127-e248.

4. Raymond V. Oliva, George L. Bakris, Management of Hypertension in the Elderly Population, The Journals of

Gerontology: Series A, Volume 67, Issue 12, December 2012, Pages 1343–1351, https://doi.org/10.1093/

gerona/gls148.

5. Musini VM, Nazer M, Bassett K, Wright JM. Blood pressure-lowering efficacy of monotherapy with thiazide

diuretics for primary hypertension. Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD003824.

DOI: 10.1002/14651858.CD003824.pub2.

Guest Lectures 189

Mental Capacity Assessment in Older Indian

Prasun Chatterjee

Assistant Professor, Department of Geriatric Medicine, AIIMS, New Delhi

Mr. Ravi, an eighty five year-old male with hypertension, moderate dementia, and chronic renal

insufficiency was admitted after a fall. As per the recent report he had stage V CKD with hyperkalemia.

He was widowed and lived in an assisted living service (ALS). He was accompanied by the

superintendent of the ALS. Mr. Ravi thought he was in a clinic and was unable to state the year. The rest

of the examination was unremarkable.

The doctor discussed the possible long-term need for dialysis with Mr Ravi, who clearly said "No."

How do you determine if he has the capacity to make decisions?

With a huge growth in the number of older adults along with massive changes in social structure, the

need of discussion about the decision-making capacity of older adults has become relevant.

Assessing capacity of an individual is task specific and deals with the process of decision making.

Capable people have the ability to identify and accept risks, thereby able to make rational decisions based

on their values, goals and knowledge.

Decision making capacity may fall along a spectrum and the ability of an individual to make decisions

often needs to be thought of in flexible terms.

During assessment of capacity the four core abilities need to be are:-

a. Expressing a choice: The patient needs to be able to express a treatment choice. Changing

one’s decision in itself would not bring a patient’s capacity into question, so long as the patient

is able to explain the rationale behind the switch. Frequent changes in the decision-making,

however, could be indicative of an underlying psychiatric disorder or extreme indecision, which

could bring the patient’s capacity into question.

b. Understanding is the ability to comprehend diagnostic and treatment-related information,

risks or benefits of the proposed treatments. The patient needs to recall conversations about

treatment, to make the link between causal relationships, and to process probabilities for

outcomes. Problems with memory, attention span, and intelligence can affect one’s

understanding.

c. Appreciation is the ability to relate diagnostic and treatment information and related

consequences to one’s own personal situation. A lack of appreciation usually stems from a

denial, based on intelligence or emotion, or a delusion that the patient is not affected by this

situation.

d. Reasoning: The patient needs to be able to weigh the risks and benefits of the treatment

options presented to come to a conclusion in keeping with their goals and best interests, as

defined by their personal set of values. This often is affected in psychosis, depression, anxiety,

phobias, delirium, and dementia. The person should have the ability to rationally evaluate and

compare treatment alternatives.

The prevalence of capacity impairment in long-term-care settings is very high, between 44% and 69%.

Pathology of decision making capacity :

The brain functions that contribute in decision-making process are centered in the cortex and frontal

lobe.

Cortical (parietal and temporal lobe) functions are involved in decision making include memory and

language. Cortical language abilities are those that affect comprehension and the ability to produce the

intended words when expressing one’s thoughts in both spoken and written communication. The ability of

190 Journal of The Indian Academy of Geriatrics, Vol. 15, No. 4, December, 2019

an individual to comprehend the information needed to make decision depends upon the ability to

understand language.

Frontal lobe functions involved in the process of making capable decisions include the abilities to

concentrate, express onself, use abstract reasoning, behaviour, concentration, decision making capacity and

problem solving (judgement). Frontal lobe dysfunction can lead to inattention that interferes with the

ability to complete necessary tasks appropriately.

Basic assessments of capacity in decision making are as follows:-

Need of Research in India: Despite the fact that mental capacity assessment provides adequate

information regarding treatment and alternatives, India is yet to have adequate tools for the assessment of

capacity. Future research in this field is the need of the hour to meet the demands of older adults in India.