The significance of drug repurposing in the future of AML treatment

A Layman’s Literature Review for the project “Characterisation of repurposed drugs as novel therapies in Acute Myeloid Leukaemia (AML)”

Abstract

Acute myeloid leukaemia (AML) is a cancer of the blood and the bone marrow which can affect any person at any stage of their life. Currently in use is a dual phase treatment course of chemotherapy that is intensive, often destructive and even fatal. Therefore, there is a large necessity for better treatment strategies to be discovered and employed. Drug repurposing can offer as a beneficial route of study into novel therapies for the treatment of AML and other diseases alike. Targeted compounds such as Bromocriptine and Tivantinib, which are specific to the indications of disease, can be studied at lower cost and with a shorter timescale. Alongside this is a lower risk of failure and the ability to use combination therapies where compounds are working in synergy. This means a greater chance of benefitting patients. Drug repurposing is not without its downfalls however. Chance findings related to reports of clinical trial members are often how a drug is found for repurposing and applying drugs with primary indications in one disease type to a completely new area often has low success. Such challenges of drug repurposing imply that greater care and study is needed before selecting it as a strategy. (199)

Introduction

Drug repurposing is the use of already known drugs, some of which successful and some failed in previous testing, as treatment for a new disease. Thalidomide, for example, seems a villainous drug to most due to causing serious birth defects in babies through use in morning sickness by pregnant women during the 1950s. Through repurposing however, it has now been shown to have a vast array of therapeutical uses such as in multiple myeloma, leprosy and Crohn’s disease (1).  The ReDO Project further put into practice this repurposing strategy and, in doing so, identified that out of 268 non-cancer drugs, 73% showed an anti-cancer effect (2). This conveys that there is a promising benefit and future in studying already known compounds for a variety of uses. Cancer is a wide term used to describe abnormal growth of cells over time. A blood cancer is a cancer which affects the blood, bone marrow and the lymphatics. Leukaemia occurs when a cell within the bone marrow, the production site of myeloid (red blood cells and white blood cells) and of lymphoid cells (B and T cells), goes rogue and multiplies greatly. Leukaemia can be further split up into acute or chronic, myeloid or lymphoid leukaemia. Acute myeloid leukaemia (AML) refers to a cancer caused by mutation (change within genes) in an immature cell of myeloid lineage whereas, chronic myeloid leukaemia would refer to one of mature myeloid lineage.

Current treatment strategies are harsh on the recipient’s body due to the nature of the chemotherapy used. In a study of 71 patients with AML, only 16 patients survived a course of chemotherapy without any adverse side reactions (3). Drug repurposing is therefore important in the world of cancer due to its identification of less toxic therapeutical compounds compared to some of those used in common therapies. Furthermore, it provides a greater chance of survival for vulnerable groups in AML, such as geriatric patients, to whom the current chemotherapy may prove more harmful than beneficial. (331)

Discussion

Drug Repurposing- Positives, Limitations and Challenges

Drug repurposing, also known as drug repositioning, is an efficient approach which cuts down on the time and money needed for development of a new drug. It has two routes, old drug against new target or old target with new drug (4). Current processes of drug identification and eventual development mean that the time scale can be up to 17 years in order to carry out the full 5 stage FDA process (see Figure 1a) (5). Drug repurposing can reduce this time to around 10-12 years through bypassing stages such as toxicity testing, manufacture and some clinical testing (see Figure 1b) (6).

Figure 1: A simplified schematic to show the process for (a) newly proposed drugs and (b) repurposed drugs.

Figures adapted from information in (5,6)

Mifepristone, an emergency contraceptive, was able to be clinically tested as a repurposed drug for Cushing’s syndrome with 28 people in comparison to a newly developed compound, levoketoconazole, which needed approximately 90 for the same use (7,8). This shows that the magnitude of further testing can be reduced and, in turn, the cost of running the testing will still be lower as well as also having a reduced time scale. On average, 40% of the cost of running a repurposed drug is reduced against that of investigating a newly developed compound (9). This is achieved through such bypasses given the repurposed drug has been approved for safe use, has a known mode of action and side effects and has its toxicity outlined through previous clinical testing. Such cut downs on time and cost through previously obtained knowledge are especially appealing when it comes to looking for treatments of rare diseases.

A rare disease is a disease such as AML, which affects a small portion of people in comparison to other diseases like coronary heart disease. For pharmaceutical companies, the negatives would outweigh the positives to begin research and development into most compounds directed at these rare diseases due to the costs of clinical testing, development and mass production whilst coupled with further losses in commercial value. This was especially true in the USA prior to the introduction of the Orphan Drug Act 1983 where only 10 products for rare diseases were approved, now rising to over 600 “orphan drug” approvals due to the incentivisation given to the companies through the initative (10).

Given the reduced cost of repurposed drugs, there is also the ability for research groups to study compounds that are directed towards these rare diseases without involving the pharmaceutical industry.

Drug repurposing is not without limitations however. Although these omitted processes and steps help reduce the risk associated with failure of drug development (see Figure 2), repurposing is not a guaranteed strategy to ensure a successful drug will be found. Failures in repurposed drugs often occur during the second phase of clinical testing (4). This however is usually not due to its pharmacokinetic profile (how the drug acts within a living organism) as there is copious information to outline such and so, reduced attrition rates.

There is also a degree of serendipity when it comes to drug repurposing, for instance, a patient has two indications and by chance, they can both be treated with exactly the same drug. A good example of such drug would be Viagra (sildenafil). Originally used to try and treat angina, a condition where reduced blood flow to the heart muscle causes chest pain, it became apparent that it was useful in the treatment of erectile dysfunction also (11). This does however rely on an individual reporting such effects.

A further challenge of drug repurposing is due to limited data relating to success rates, especially high ones. A drug which is successful for initial use which is applied in the same area i.e. one type of cancer drug being used to treat another, can give high success rates. It changes however when you apply a drug to a completely different area, with a large decrease in success. This is even more substantial with drugs that have failed initial indication (12). This opposes the main idea for use of drug repurposing as, in most cases, the desired outcome is to treat in a completely new area. (679)

Figure 2- A graph showing the risk against reward of various drug strategies.

Note the position of drug repositioning as low risk and high reward in comparison to other common strategies. *Small markets refers to development of drugs for rare diseases and has been backed by acts such as the Orphan Drug Act.

Figure taken from (6)

Acute Myeloid Leukaemia and Drug Repurposing

Acute Myeloid Leukaemia is a cancer of the blood and bone marrow. Specifically, it is the overproduction and overpopulation of immature myeloid cells due to a failure in differentiation (becoming more specialised) which, in turn, impede the bone marrow from its function of creating healthy blood cells. As a result, the decreased number of mature white cells leads to frequent infection and decreased red cells leads to anaemia. Furthermore, pain in joints and bones is common due to the vast number of leukemic cells.

AML is the most common leukaemia found in adults. Although it can occur at any stage of life, the average age of diagnosis is 68 (13). Age plays an important role in the overall survival (OS) of AML patients as, for a diagnosis made before the age of 45, there is a 60.4% relative 5-year survival which decreases to 7.9% when the age is above 65 for all races and both sexes (14). Typically, there are two phases for treatment of AML, induction therapy and post-remission/maintenance therapy in respective order. The aim of induction therapy is to kill as many of the leukaemia cells as possible through use of agents such as cytarabine and daunorubicin resulting in less cancer through the body or no cancer at all, called partial/complete remission respectively. Around 60-80% of patients below and 40-60% of patients above 60 years old enter complete remission (15).

Treatment for AML has remained relatively standard since the “7+3” treatment began in 1973. 7 days of cytarabine followed by 3 days of daunorubicin. This treatment carries side effects of bleeding, vomiting and hair loss. Furthermore, the intensive treatment of AML is renowned for carrying a complication of treatment related mortality (TRM), death due to treatment. TRM is also related to age (16). Cytarabine has however been found to be effective at low doses in elderly unfit for aggressive treatments (17). Although this is generally regarded as the “gold-standard” drug for chemotherapy, resistance caused relapse is frequent and overall survival of patients remains low (18). Induction therapy is usually followed by allogenic haematopoietic stem cell transplant, a treatment involving a transplant of an acceptable donor’s stem cells into the patient, which has potential curative outcomes. This again is wearily used due to the comorbidities, weakness, resistance to treatment and incidence of secondary AML associated with increased age (19). This therefore highlights the necessity for a treatment which is less detrimental to the health of the recipient, especially given the correlations with age and complications are so strong, noting again that median age is 68.

AML is not one disease, but a disease consisting of many subtypes. In addition, there exists a vast amount of molecularly distinct subtypes which are also age-specific (20). This enforces the need for novel therapies related to the age of the patient as a one for all based therapy will not produce an effective outcome for all patients.

Bromocriptine is a drug used to treat hyperprolactinaemia, Parkinson’s and peripartum cardiomyopathy (21). The associated side effects are minimal, most reporting only nausea. A recent repurposing study into bromocriptine has shown it to have an anti-cancer (cytotoxic) specificity for leukemic cells, causing arrest of proliferation and triggering death of the cells via apoptosis. This drug also shows a marked cooperative effect (synergy) with the previously used cytarabine, meaning a greater positive acceptance (17).  This is a promising discovery into therapy for AML as it resets the trend of the toxic and widely acting chemotherapeutical treatments used which cause various adverse side effects. A directed treatment, specific to leukemic cells is of much greater value as it acts in a targeted manner to address the problem. A removal of associated TRM further means a potential therapy for paediatric and geriatric patient groups.

GSK3 is an important kinase involved in many normal cell pathways such as transcription, apoptosis and stem cell regulation. In cancer it is found to be self-contradictory however, causing pathways which are usually down-regulated to be upregulated. As a result, it plays a supporting role in the maintenance of cancer and specifically in AML (22, 23). A further repurposed drug for use against AML has been found in the form of Tivantinib. This drug was previously used as a MET inhibitor and has now been used to target and inhibit GSK3 and GSK3. It causes a potent inhibitory effect on the reproductive ability of cells in the bone marrow of AML patients as well as inducing apoptosis and differentiation (increased specialisation). Another desirable trait of Tivantinib is that it can act in synergy with another anti-cancer drug, ABT-199. This acts on BCL-2, an anti-apoptotic protein upregulated by cancer cells. This is important in AML as the current approved FDA compounds for GSK inhibition consists of only one, LiCl, with disputable strength as a therapy due to its non-specificity for GSK3 (24). Given the specificity of Tivantinib and its ability to be used in combination therapy with ABT-199, it poses as an exciting and promising novel repurposed drug for AML. This is something which is greatly needed due to the lack of success and toxicity associated with the traditional AML treatments. (862)

Conclusion

Drug repurposing is a promising route of drug “discovery” for introduction of novel disease therapies. Although often serendipitous, supplication of compounds for use in a shorter time gives a promising future for disease. Lower costs associated also mean a more appealing environment for the pharmaceutical industry and even for research groups outside the industry. As a result, rare diseases like AML are more likely to have novel therapies studied. AML is in need of a less intensive, less toxic regime for treatment. High relapse rates as well as poor overall success associated with current chemotherapy do not give much promise to patients or physicians alike. Repurposed drugs with high specificity for leukemic cells or targets within leukaemia, such as Bromocriptine or Tivantinib, give a much-needed boost to successful treatment with added benefits of lower toxicity and TRM. Greater research is however needed into repurposing drugs in order to ensure the low risk of failure and to keep an exciting field of study worthwhile over

de novo

practices. (167)

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Dementia is one of the leading causes of nonfatal disability in the developed world and by 2030 it is predicted that dementia will be the third leading cause of the years of life lost due to death and disability .Measured using the concept of disability adjusted life years (DALYS) which combines a measure of the average years of life lost due to disease with the years lived with disability Mather’s and loncar (2006). Alzheimer’s society describes dementia as a term used to describe various different brain disorders that have in common a loss of brain function that is usually progressive and eventually severe there are over 100 different types of dementia. (All Parliamentary party groups on dementia 2009) reports, there are approximately 700,000 people in the UK today with dementia. That number will double up within 30 years and the financial cost of the dementia today is more than the cost of heart disease, cancer and stroke combined. In global burden disease WHO( 2003) it was estimated that disability from dementia is higher than almost all conditions with the exceptions of spinal cord injury and terminal cancer .Dementia is a health and social care challenge of scale, we can no longer ignore it and government recognized this with national dementia strategy for England in February( 2009). Dementia is a significant life changing process affecting everyone in different ways .Different type of dementia affects individual people differently. My case study is about Mr. Roy who is diagnosed with Fronto temporal dementia who has progressive language loss and cognitive decline. As he suffers from primary progressive aphasia, all information gained from his wife .Jane. [I have changed all names of persons and places to protect confidentiality as followed by NMC guidelines.]

Mr. Roy was a supervisor and driver for a company for 35 years, dedicated employee, he married Jane and had four children. Roy’s mum has history of undiagnosed psychotic problems. He always had abrupt mannerism, strict with everything and always wanted to be first. Although he was dedicated to his job and never had time for his family, Jane was the main carer of the family. She worked as manager of a residential home .She says that he never been there for my children. Roy was a lovely person when he married her, after she had four children, he was working as a supervisor for a company for 35 years. Roy lost his job when he could not accept the changes in work environment, when the company started to use the modern equipments. He started to behave inappropriately, he collected office documents and kept it on the top of the attic, as he does not like Changes Company’s policies .He lost his job as this company moved to another place. He lost interest in his family life; he spent time in pub and always had temporary lady friends and spends money for them, which always leaded him to have debts and borrowed from banks and building society, without knowing his wife. His wife had to face the summonses, bills and police cases for a long time. She continued to pay back .He had problems with managing accounts, records and names of children. Roy started to be very rude and argumentative pressure on his wife for money and spent it treating others in the pub. He had lots of temporary lady friends; his personality changed, he threatened his wife with a gun one day to find his way. His driving skills became poor, and he had a car crash but survived miraculously. He never mentioned with his car after this incident. Mr. Roy then isolated himself .He use to visit regularly to the place where the company was and travelled several times in a bus on the fixed route. He has been referred to the psychiatrist and diagnosed of anxiety, depression and he refused to undergo any treatment for 3 years. His condition become worse .Roy’s memory deteriorated. He admitted to the hospital due to his difficult behaviour pneumonia Mrs. Jane had to take voluntary retirement due to financial commitment and to look after Roy. Her daughter was very supportive to her other three children hated him, and never bothered about their dad. Roy then sectioned due to his difficult behaviour admitted in mental health unit, undergone a CT scan and diagnosed of Fronto temporal dementia. He moved to an EMI nursing home to manage his complex needs. Roy displays physical aggression both actual and threatening. Roy says “do you want two black eyes.” He will raise his fist and will attempt to slap the staff’s faces. Roy’s inhibitions appears reduced which often results in socially inappropriate behaviours .Physical aggression towards fellow residents, Roy appears to have no insight to his own condition on others illness and safety. Roy is at high risk of absconding and has a past history of windows and absconding from the previous care settings .Roy is self neglect ,resistive towards personal care , his behaviour can be challenging when staff approach him regarding personal care .He has no concept of risk to himself or others ,he will invade people’s personal space and can become confrontational regardless of any age groups .When people ask Roy questions he will laugh inappropriately, mimic ,or answer inappropriately ,for example ‘don’t be stupid .His short term memory appears impaired to the place and date .Long term memory appears impaired and muddled . Roy believes that he was in the Navy, but his wife has told that this was incorrect .Some aspects of Roy’s long term memory are intact and he is able to recognize family members He likes to wear coat and tie all the time .Conversational skills are limited and superficial in style therefore further mental health assessment are difficult. Roy likes music and will play loud music with no concept to others. When his mood lowers Roy has a tendency to socially isolate himself ,He is currently prescribed antidepressants and his mood currently appears stable ,he has a sweet tooth , can be very demanding for particularly chocolate éclairs .He tends to get chest infections recurrently.

Common causes of dementia are Alzheimer’s disease ,vascular dementia ,Korsakoffs syndrome ,Dementia with Lewy bodies Fronto temporal dementia ,Creutzfeldt Jacob syndrome ,Aids related cognitive impairment ,other rarer causes like Progressive Supranuclear palsy, and Bins angers disease. People with multiple Sclerosis, motor neuron disease, Parkinson’s disease and Huntington’s disease can also at an increased risk of developing dementia.

Younger onset of dementia is arbitrarily defined as beginning before the age of 65 years. It is much rarer than late on set of dementia (Harvey, 1998) the proportion of those with Fronto Temporal Dementia is thought to be higher in younger-on set group than among older people developing dementia. (Dale2003; Williams 2001) possibly posing stresses for family members. In addition , the social and psychological context of younger people with dementia is different from that of older people (Cox and Keady,1999; Tined all and Manthrope,1997)The term Fronto temporal dementia covers a range of condition including picks disease and dementia associated with motor neuron disease all are caused by damage to the frontal lobes and the temporal parts of the brain, these are responsible for the emotional responses and language skills Alzheimer’s society (factsheet404)explains the core features of FTD as defined by the Neary criteria are early decline in social and personal conduct, emotional blunting and loss of insight. Selective brain degeneration is seen in dorsolateral orbital and medical frontal cortex (Neary).Personality shifts in the direction of submissiveness are typical for FTD. Although extroversion can emerge in previously introverted individual s(Rankin, Kramer, Mychackand Miller(2003) points out that there is a shift from the warmth to coldness on personality scares .Changes in established religious or political believes and patterns of dress suggesting changes in the sense of self are common, respect for personal boundaries disappears, some patient stare and become overfriendly, taking openly to the strangers(including children),Increased trust for others make these patients vulnerable to financial scams or sexual exploitation. Indiscretion causes embarrassment to the family and disinhibited verbal outbursts or socially inappropriate behaviour is common. Miller (1997) describes the symptoms are Antisocial behaviours, often reflect poor judgement and impaired impulse control. Impairment in personal conduct is a core feature .Some can be overactive with verbal and motor activities .where as others become inactive and withdrawn, some patients will fluctuate between over activity and apathy. Gregory and Hodges (1996)Kean Kalder, Hodges and young ,(2002),Rosen et al,(2004)Loss of concern for others and prominent emotional blunting tend to isolate the patient .A consolation of cognitive and emotional changes tocontributeto this emotional blunting .for example ,comprehension and expression .are deficient , and the inability to comprehend the emotions that others are feeling. That the others are feeling particularly better, negative emotions contributes to the feeling that the patient is no longer concerned about his or her loved ones, in addition, patients become self centred and tend to focus on their own particular needs and desires. In a medical crisis setting, patients may respond with inappropriate lack of concern , sometimes in a bizarre manner (Johansson & Hagberg,1989;Kramer et al: 2003) loss of executive functions leads to impaired multi tasking , shifting abstracting , making sound judgments , planning and problem solving the executive problems can be the first manifestaon of std proceeding behavioural deficits ( lindauetal ; 2000) poor performance at jobs leads these patients to get fired , and they tend to work at progressively simpler occupations. Similarly, catastrophic financial loss due to poor decision making is common prior to presentation at the physician’s office (miller 1995) explains that preservative and stereo typed behaviours emerge in the middle stages of FTD, simple repetitive motor or verbal acts such as lips making, hand rubbing or humming are common. More complex behaviours such as collecting (garbage, rocks, stamps, plastic figures) wandering a fixed route or counting money, evolve in patients. Hyperorality manifests in over eating and changes in food preference to a certain type of food or even conception of inedible objects. Analysing this behaviour characteristics Mr Roy is exactly the same features we can see in him .Roy’s challenging behaviour can be the signs of distress anger, aggression anxiety, and withdrawal .As ( Kerr and Cunningaham2004 ) states that it is difficult to determine how person respond to the behaviour or responses of a person with dementia ,if we do not know what caused it for and how person interprets it .As Roy has a rare form of dementia with primary progressive dysphasia

Patient with FTD also go on to develop speech and language problems during the evolution of disease, (Neary 1998 Pasquier, Lebert, Lavenu and Gallium, 1999).

Depression occurs and many patients with FTD are diagnosed with depressive disorders before dementia is evident (miller 1991) depression has atypical features that are a clue to the real diagnosis. Loss of insight regarding behavioural changes, diminished empathy for others, denial of depression, changes, diminished empathy for others, denial of depression, apathy, and blunted affect are present, in many patients with FTD and depressive features. Psychotic features, such as delusions and hallucination, occur but are infrequent. Deficits in working memory, set shifting and generation are evident, episodic memory deficits can be prominent, leading to misdiagnosis of AD. (Lindau 2000) (Miller, Swartz Lesser, & Darby, 1997) states that excessive smoking and alcohol or drug abuse can lead to the misdiagnosis of alcohol or drug addiction, patients with FTD tend to overeat in gluttonous manner. In clinical practice because many physicians are unfamiliar with its specific features FTLD is commonly misdiagnosed as AD. Decline in social and personal conduct, emotional blunting, loss of insight and progressive speech disorder develop early in the FLTD.

(Dawn Brooker 2007) points out that understanding person’s past history is crucial to providing person centred care, by looking at procedures for how key stories are known about and how these are communicated Person with dementia is central to this process although others such as family or professional carers can also derive considerable benefits from being involved . The process and its tangible outcomes assist communications and aid the development of positive relationships, Life story work therefore has a multiple benefits for various people. It is and activity that all the largely about the past, takes place in the present .it involves a series of intensive, non threatening highly personal discussions between the person disabled by dementia and responsive appreciative listener .As Roy’s dementia has progressed and is unable to gain any information from him . Cunningham (2006) Lack of awareness and knowledge about the needs of the patients with dementia can lead to challenging behaviour and misinterpretation of their needs. The ABC analysis of behaviour is a useful successful tool for understanding patients with Dementia. This system provides an opportunity to record all the factors which interact to create a challenging situation. (Wang and miller 2006) points out that many aspects of this disorder make it particularly troublesome for caregivers, including loss of empathy for others, apathy, diminished insight and inappropriate sound behaviours that characterize these patients. It can be argued that successful caring relationships are those here the person with Dementia is accepted just for what they are, not pressurised to become what they once were an impossible target for them to achieve.

Kitwood was the first writer to use the term ‘personhood’ in relation to people with dementia, he defined personhood as a standing or status that is bestowed upon what human being by other, in the context of the relationship and social being .It implies recognition, respect and trust. Brooker (2004) helpfully encapsulates the person -centred frame work in four areas valuing the person with dementia and those who provide care for them.(V)The individuality of each person with dementia ,(I),The important perspective of person with dementia (P) and the key role played by persons social environment person centred care involves the integration of these four elements. So the people with dementia and those who care for then truly seen as VIP`s.

A senses frame work has been proposed by Nolan as a of understanding these triangular relationship between the person with dementia ,the relative and the care home staff .Six senses are highlighted .those are – sense of security ,sense of belongings ,sense of continuity ,sense of purpose ,sense of achievement and sense of significance .For person with dementia living in a care home the two key sets of triangle relationship are first ,with family members and friends and second, with various members of staff provide care .the relationship with family and friends is vital in the context of the persons journey through life; the relationship with staff is vital in relation day to day comfort and satisfactions needs .Nolan et al argues (2003;2006) argue that these six senses are essential for the relationship that are mutually satisfied for all concerned .for each of six areas ,the person with dementia ,family member and care worker may experience this differently ,yet a gap in any of these areas will adversely affect the quality of relationship.

(Woods ;Keady; b’seddonch ;Diane 2007)explains that the person with dementia may feel secure and safe when he or she has a friendly smiling faces around, and physical needs are responding to promptly and gently (the family member may feel secure when she or he feel confident that the person is in good hands . and receiving good care .the care worker may feel secure when their job is not under threat . when they do not feel criticised and scrutinised for every action, and when they do not feel under threat or attack, whether physical or verbal. A study by CSCI (2008) of care homes has shown the quality of care staff, communication with people with dementia has a major impact on their quality of life .leadership ethos, of care home staff training; support and good development are crucial factors in supporting good practice.

Jane hated Roy because his difficult behaviour and the stress she had before diagnosis. G.P`s were not aware of this dementia as it is rare form of dementia ,.A fundamental way facilitating carer’s involvement, is for the nurses and the carers to negotiate a relationship within which involvement can operate in a way that endorses the principles of good practice is already established .Walker. E and Jane, B (2001)

Fronto temporal lobe degeneration strikes at relatively young age, so the disease often causes dramatic economic and social consequences before patients arrive in the clinic. The UK National service frame work for older people states that there should be specialist services for the younger people with dementia[DOH],(2001)National service frame work for long term Neurological Conditions advices that there should be person centred services ,early recognition ,prompt diagnosis treatment and early rehabilitation(DoH,2005)

When Jane had to face the consequences of the challenging behaviours financially and emotionally for long periods as she was not getting enough help from the health professionals ,and lack of diagnosis and unaware of his type of dementia .the person with dementia will adjust with this naturally ,but it can be much more difficult for their loved ones, since they are distressed by what they lost .

Miller and Wang (2003) Typical and Atypical antipsychotics have been used for controlling aggressive and psychotic symptoms. However considering the possible adverse response with deteriorating motor symptoms and dysphasia, antipsychotics should only be used as a last resort.

An increasing number of structured or therapeutic activity-based interventions exist for people with dementia. Examples include reality orientation; cognitive stimulation therapy; music therapy; art, writing, dance and movement; drama; aromatherapy and sensory stimulation; intergenerational programmes Montessori-based methods; doll therapy; the SPECAL approach; emotion-oriented care; horticultural therapy and woodlands therapy. Reviews have revealed that the research evidence for most of these activities appears weak, however the visible positive effect they have on individuals and anecdotal evidence indicates that they are worthwhile and have

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Kerr D. Cunningham c(2004)Finding the right response to people with Dementia .Nursing and residential care .6,11, 539-542.

Harvey R.J (1998) Family Burden young onset of dementia Epidemiology, clinical symptoms, support and outcome London Imperial College.

Walker E. & Devar B.J. (2001) issues and innovations in Nursing Practice .How do we facilitate carer ‘involvement in decision making? Journal of advanced Nursing 34(3) , 329-337.

Conclusion

The above study thus explains the severity of Dementia and its consequences if left unattended. As stated above the number of people getting affected by this disease is increasing at a very high rate. Thus this disease seems to pose a serious threat to mankind and its social existence. The time has come to commence large scale studies and experiments on this disease and thereby device a methodology/cure for this. Also WHO should promote awareness about this disease among common public to ensure early detection and thereby reducing further health risks.

INTRODUCTION

Communication is a process and has many aspects to it. Communication is a dynamic process by which information is shared between individuals (Sheldon 2005). This process requires three components (Linear model Appendix figure 1.1), the sender, the receiver and the message (Alder 2003). Communication would not be possible if any of these components are absent. While Peate (2006) has suggested that communication is done every day through a linear process, Spouse (2008) argues that it is not so simple and does not follow such a linear process. He explains that due to messages being sent at the same time through verbal and non- verbal avenues, it is expected the receiver is able to understand the way this is communicated.

Effective communication need’s knowledge of good verbal and non-verbal communication techniques and the possible barriers that may affect good communication. The Nursing and Midwifery council (2008) states that a nurse has effective communication skills before they can register as it’s seen as an essential part of a nurse’s delivery of care. (WAG 2003)

Reflecting on communication in practice will also enforce the theory behind communication and allow a nurse to look at bad and good communication in different situations. This will then enforce the use of good communication techniques in a variety of situations allowing for a more interpersonal and therapeutic nurse patient relationship.

This assignment discusses health care communication and why it is important in nursing by:

Exploring verbal and non-verbal communication and possible barriers

By exploring the fundamentals of care set out by the Welsh assembly and the nurse and midwifery council’s code of conduct a better understanding of the importance of communication is gained.

Reflecting in practice using a scenario from a community posting.

VERBAL COMMUNICATION

Verbal communication comes in the form of spoken language; it can be formal or informal in its delivery. Verbal Language is one of the main ways in which we communicate and is a good way to gather information through a question (an integral part of communication) and answer process (Berry 2007; Hawkins and Power 1999). Therefore verbal communication in nursing should be seen as a primary process and a powerful tool in the assessment of a patient.

There are two main types of questioning, open-ended questions or closed questions (Stevenson 2004). Open-ended questions tend to warrant more than a one word response and generally start with what, who, where, when, why and how. It invites the patient to talk more around their condition and how they may be feeling and provoke a more detailed assessment to be obtained (Stevenson 2004). The use open-ended questions make the patient feel they have the attention of the nurse and they are being listened too (Grover 2005). It allows for a psychological focus to be given, this feeling of interest in all aspects of the patients care allows for a therapeutic relationship to develop (Dougherty 2008).

Closed questions looks for very specific information about the patient (Dougherty 2008). They are very good at ascertaining factual information in a short space of time (Baillie 2005).

There are two types of closed questions: the focused and the multiple – choice questions. Focused questions tend to acquire information about a particular clinical situation (e.g. asking a patient who is been prescribed Ibuprofen, are you asthmatic?) whereas multiple choice questions tend to be more based on the nurse’s understanding of the condition being assessed. It can be used as a tool to help the patient describe for example the pain they feel e.g. is the pain dull, sharp, throbbing etc (Stevenson 2004).

For verbal communication to be effective, good listening skills are essential. Sharing information, concerns and feelings becomes difficult, if the person being spoken to doesn’t look interested (Andrews 2001). Good active listening can lead to a better understanding of the patients most recent health issues (Sheldon 2005). Poor listening could be as a result of message overload, physical noise, poor effort and psychological noise. Therefore being prepared to listen and putting the effort and time are essential in a nurse’s role (Grover 2005).

NON-VERBAL COMMUNICATION

This type of communication does not involve spoken language and can sometimes be more effective than words that are spoken. About 60 – 65 per cent of communication between people is through non – verbal behaviours and that these behaviours can give clues to feelings and emotions the patient may be experiencing (Foley 2010, p. 38). Non-verbal communication adds depth to speech; to re affirm verbal communication; to control the flow of communication; to convey emotions; to help define relationships and a way of giving feedback. The integration between verbal language and paralanguage (vocal), can affect communication received (Spouse 2008)

Berry (2007, pg18) highlights the depth of verbal language due to the use of paralinguistic language. The way we ask a question, the tone, and pitch, volume and speed all have an integral part to play in non – verbal communication. In his opinion, personality is shown in the way that paralanguage is used as well as adding depth of meaning in the presentation of the message been communicated.

Foley (2010) identifies studies where language has no real prevalence in getting across emotional feelings, in the majority of cases the person understands the emotion even if they don’t understand what is being said. Paralanguage therefore is an important tool in identifying the emotional state of a patient.

Non-verbal actions (kinesis) can communicate messages, such as body language, touch, gestures, facial expressions and eye contact. By using the universal facial expressions of emotion, our face can show many emotions without verbally saying how we feel (Foley 2010) refer to Appendix table 2. For example, we raise our eye brows when surprised, or open our eyes wider when shocked.

First impressions are vital for effective interaction; by remembering to smile with your eyes as well as your mouth can communicate an approachable person who is open. This can help to reassure a patient who is showing signs of anxiety (Mason 2010).

BARRIERS TO COMMUNICATION

An understanding of barriers in communication is also very important. The Welsh Assembly’s fundamentals of care (2003) showed that many of the problems associated with health and social care was due to failures in communication. These barriers may be the messenger portraying a judgmental or power attitude. Dickson (1999) suggested that social class can be a barrier to communication, feeling inferior to the nurse may distort the message being received, making communication difficult to maintain.

Environmental barriers such as a busy ward and a stressed nurse could influence effective communication. This can greatly reduce the level of empathy and communication given as suggested by Endacott (2009).

People with learning disabilities come up against barriers in communicating their needs, due to their inability to communicate verbally, or unable to understand complex new information. This leads to a breakdown in communication and their health care needs being met (Turnbull 2010).

Timby (2005) stresses that when effectively communicating with patients the law as well as the NMC (2008) guidelines for consent and confidentiality must be adhered to. This also takes into account handing over to other professionals. He suggests that a patient’s rights to autonomy should be upheld and respected without any influence or intimidation, regardless of age, religion, gender or race. The use of communication in practice is essential and reflecting on past experience helps for a better understanding of communication, good and bad.

REFLECTION

Reflecting on my experience while on placement in a G.P with a practice nurse in south Wales Valley’s, has helped me understand and gain practical knowledge in communicating effectively in nursing practice. The duration was for one week and includes appointments in several clinics to do with C.O.P.D (Chronic obstructive pulmonary disease). I will be reflecting upon one appointment using the Gibbs’s reflective cycle (1988).

Description

Due to confidentiality (NMC, 2008) the patient will be referred to as Mrs A.E. The Nurse called Mrs A.E to come to the appointment room. I could see she was anxious through her body language (palm trembling and sweaty, fidgety, calm and rapid speech). The nurse asked her to sit down. The nurse gained consent for me to sit in on her review (NMC, 2008).

The review started with a basic questionnaire the nurse had pre generated on the computer. It was a fairly closed questionnaire around her breathing including how it was, when it was laboured. Questions were also asked around her medication and how she was taking her pumps. Reflecting on these questions, I feel the questions did not leave much opportunity for Mrs A.E to say anything else apart from the answer to that question. The nurse controlled the communication flow. The Nurse did not have much eye contact with the patient and was facing the computer rather than her patient. I wondered if the nurse had notice the anxious non-verbal communication signs. The patient seemed almost on the verge of tears, I wasn’t sure if this was anxiety, distress from being unwell, or she was unhappy about something else. I felt quite sorry for her as all her body language communicated to me that she was not happy. She had her arms crossed across her body (an indication of comforting herself) and she did not smile. She also looked very tense and uncomfortable.

The Nurse went on with the general assessment and did the lung test and I took the blood pressure and pulse, gaining consent first as required by the NMC. Once all the questions had been answered on the computer the Nurse turned to face Mrs A.E and I noticed she had eye contact with her and had her body slightly tilted toward the patient (non verbal communication). The Nurse gave her information on why her asthma may be a bit worse at the moment and gave her clear and appropriate information on how she can make manage her COPD at this time of year. The Nurse gave her lots of guidance on the use of her three different pumps, and got her to repeat back to her the instructions, to make sure she understood. I could feel the patient getting more at ease as the communication progressed and also on the confirmation that she understood the instruction. The Nurse knew this patient well and then set the rest of the time talking to the patient about any other concerns she had and how she was feeling in herself, using a more open question technique.

The nurse used her active listening skills and allowed the patient to talk about her problems and gave her empathy at her situation as well and some solutions to think about. She gave the patient information of a support group that helped build up confidence in people with chronic conditions and helped them deal with the emotional side of their condition.

Feelings

After the patient had gone, my mentor explained that the patient was a regular to the clinic, she had many known anxiety issues which weren’t helped by her chronic asthma.

Through-out the beginning of the review I felt very awkward. I thought, because I was sitting in on the review, may have been the reason the lady had not said why she seemed so anxious and upset. I also felt the nurse was not reacting to the sign of anxiety from Mrs A.E and this made me feel uncomfortable. I felt like I wanted to ask her if she was ok, but felt that I couldn’t interrupt the review. However by the end of the review I felt a lot better about how it had gone. I did feel that by building up a relationship with the patients allowed the nurse to understand the communication needs of the patient and also allowed her to use the time she had effectively. She used empathy in her approach to the lady and actively listened to her. I understand that the start of the review was about getting the facts of the condition using a lot of closed questions, whereas the later part of the review was a more open questions and non verbal communication approach, allowing the patient to speak about any concerns and feelings about those questions asked earlier.

Evaluation

Effectively using closed questions allow for a lot of information to be gathered in a short space of time, and can be specific to the patients review needs. These pre-generated questionnaires are good at acquiring the information needed by the G.P. and also for good record keeping which are essential in the continuity of care delivered to the patient (NMC 2008). It can also protect the nurse from any litigation issues.

The use of open and closed questions also allowed for the review to explore the thoughts and feelings of the patient, thus allowing for empathy from the nurse and is considered a vital part of the counselling relationship (Chowdhry, 2010 pg. 22).

However the use of the computer screen facing away from the patient, did not allow for good non-verbal communication skills to be used. The lack of eye contact from the nurse may have exacerbated the anxiety felt by the patient. Hayward (1975, p. 50) summarised in research that anxiety highlighted an uncertainty about illness or future problems. This link to anxiety was also linked to increased pain.

Nazarko (2009) points out, it is imperative that a person has the full attention of the nurse when they are communicating. He states that being aware of one’s own non-verbal behaviours, such as posture and eye contact can have an effect on how communication is received by the patient.

As evident in the reflection, the patient at the beginning of the review was anxious, upset and worried. By the end of the review her body language had significantly changed. The patient looked and felt a lot better in herself and had a better understanding of how her condition was affecting her and understood how to manage it. However if this information was badly communicated, the patients anxiety could have been prolonged (Hayward, 1975). This also links back to the need to understand medical conditions so that communication is channelled to the patients’ needs at the time. The fundamentals of care set out by the Welsh Assembly Government (2003), states that communication is of upmost importance in the effectiveness of care given by nurses. By looking at all the fundamentals of communication and the effect on patient care we can understand and recognise that the communication in this reflection was good communication in practice.

Analysis

The closed questions were used at the beginning of the review, had their advantages. They allowed the nurse to focus the on the specific clinical facts needed. The start of the review used mainly closed questions to get all the clinical facts needed to be recorded, such as Personal information, Spirometry results, blood pressure, drug management of COPD (Robinson, 2010). The structured approach allows the nurse to evaluate using measurable outcomes and thus interventions adjusted accordingly (Dougherty, 2008). The closed question approach allows the consultation to be shortened if time is an issue. However the disadvantage of this as identified by Berry (2007) is that important information may be missed. The use of closed questions on a computer screen hindered the use of non-verbal communication. Not allowing for eye contact, which is an important aspect of effective communication.

The use of open questions in the review allowed the patient to express how they were feeling about their condition or any other worries. The nurse used active listening skills, communicated in her non-verbal behaviour. It gave the opportunity to the patient to ask for advice on any worries they might have. The use of open questions can provoke a long and sometimes not totally relevant response (Baillie, 2005), using up valuable time.

Eye contact is another important part of communication in the reflective scenario. The eye contact at the start of the review was limited. The nurse made slight eye contact when asking the closed questions, but made none when given the answer. This may have contributed to the patient’s anxious state. However, the eye contact given during the open questions section. At this stage, there were several eye contacts between the nurse and patient and information was given and understood. The value of eye contact in communication is invaluable and has great effect at reducing symptoms of anxiety (Dougherty 2008).

Reflection conclusion

The use of communication in this COPD review was very structured. The use of closed questions helped to structure the consultation and acquire lots of information from the patient. The open questions allowed for the patient to express any feeling or concerns. The nurse used verbal and non-verbal communication methods, to obtain information about the patient; assess any needs and communicate back to the patient, within the time period. However in my opinion, if the computer screen was moved closer to the patient during the closed question section, better interaction could have been established from the beginning. It would also allow the nurse to look at the patient when asking the questions leading to a more therapeutic relationship, whilst still obtaining and recording a large amount of information.

Therefore, the use of effective communication skills as seen in this review along with a person centred approach can significantly increase better treatment and care given to the patient (Spouse, 2008) and thus signifies good communication in practice.

Action Plan

The goal of the plan is to increasing patient participation in the use of the computer as an interactive tool. By allowing the patient to see what is on the screen and being written, allows the patient to feel more involved in the assessment and takes away any feeling of inferiority from social class difference.

In attempt to achieving these goals, the following steps would be taken:

Set up a team to investigate the issue which could involve nursing staffs or other hospital staffs.

Drawing up a feedback questionnaire, to investigate how patients feel about the closed questions on the computer, including a section on how they would feel if they were allowed to look at the screen.

Collation, analysis and review of the results of the feedback

Identify barriers to the implementation of the plan (e.g. willingness of nurses to this change).

Inform the NMC on the issues and the findings from the feedback questionnaire.

Implementation of the plan.

Set up a monitoring and evaluation team to see if the plan is being implemented appropriately.

CONCLUSION

This assignment has looked at communication and its importance in nursing practice. Communication is thus an important process involving the interaction between one or more persons using verbal and non-verbal methods. Understanding the barriers to communication contributes significantly to how effective a nurse communicates in practice. The use of questioning in nursing has been a valuable tool in assessing a patient and obtaining information. However the way this is done can have an effect on the development of empathy, trust, genuineness and respect, between the nurse and the patient. It is imperative for nurses to however reflect on their communication in practice to further improve the therapeutic relationship between them and the patient as has been identified as essential in the delivery of care (WAG 2003).

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