ii. The use of CRISPR-Cas9 as an alternative therapy to combat antibiotic resistance

Antibiotic overuse coupled with the rapid evolution of bacteria in response has resulted in the spread and increase in antibiotic resistant infections worldwide.  This has led to a growing need to research viable alternative treatments providing a more effective strategy for dealing with such infections.

Using a combination of primary studies and secondary, summary papers the use of alternative therapies, with a focus on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and its associated protein 9 was reviewed and its viability discussed.  The most concerning bacteria to healthcare workers are the six bacteria which cause antibiotic resistant infections – Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter species, or ESKAPE bacteria.

Alternative therapies to infections caused by these bacteria include, but are not limited to, the use of lysins, probiotics, faecal transplants, bacterioricins, and bacteriophages.  Studies show some success in the use of lysins and faecal transplants although recent problems with faecal transplants indicate further research is required.

Additionally, the use of CRISPR and its associated proteins to alter genomes offers an exciting opportunity to explore.  Horizontal gene transfer (HGT) between bacteria is a key way in which antibiotic resistant genes spread.  An important area of research is the prevention of HGT.  CRISPR-Cas9 has been used effectively to prevent conjugation in

Staphylococcus

spp using the insertion of mutations, the deletion of sequences, and shown the importance of the Cas protein to achieve this.  CRISPR-Cas9 is an important tool in science and research concerning its use in the challenge of antibiotic resistance is valuable.  Although success has been shown in the alteration of bacterial genomes and the prevention of HGT, further work must be done to support the initial studies and to combat the current disadvantages of the method; the cost and the large scale applications.

(299 words)

i.The use of CRISPR-Cas9 as an alternative therapy to combat antibiotic resistance

Antimicrobial resistance (AMR) and the infections caused by antibiotic resistant bacteria is a growing problem which is predicted will lead to the deaths of 10 million people annually by 2050 (de la Fuente-Nunez

et al.

, 2017).  As well as the impact this will have on the structure and provision of healthcare, it will also impact the environment and on society socially and economically.  In response to AMR, scientists have been studying alternative ways to combat antibiotic resistance.  One such method is the use of Clustered Regularly Interspaced Short Palindromic Repeats and associated protein 9 (CRISPR – Cas9) system of defence which exists naturally within bacteria (Bikard

et al.

, 2012)  In order to research the history of antibiotic resistance and the steps taken using CRISPR to combat it Web of Science was utilised to search for antibiotic resistance in order to gain a background to the subject.  This led to an article titled ‘Alternatives to conventional antibiotics in the era of antimicrobial resistance’.  This was good overview of the methods to combat antibiotic resistance which are currently being studied and focused my search on research involving CRISPR.  I followed up on the most relevant articles referenced within this paper and started to use search terms which were relevant to these, including ‘CRISPR-Cas’, ‘sequence specific antimicrobials’, and ‘RNA guided’.  Once papers had been organised into the objectives they were suited to using Endnote, notes were made under the heading of each objective.  This aimed to organise the key points for the study and could be used as a starting point for writing the review.  My study has been focused on the following objectives;

1. Discuss the history, biology of and global impact of antibiotic resistance and the emergence of antibiotic resistance genes in microbes
2. Briefly compare and contrast the alternative therapies available to treat infections caused by resistant bacteria
3. Discuss the biology and use of bacteriophages as a delivery method of DNA into bacteria and the effectiveness of this approach
4. Describe the use of the CRISPR-Cas system as an alternative therapy to bacterial infections and the modes of action employed in this approach
5. Critically analyse the research evidence for the benefits and pitfalls of CRISP-Cas9 as a therapy
6. Discuss the future of CRISPR-Cas9 and the opportunities for further research

The scope of this literature review covers alternative therapies to antibiotics and will not cover the development of, or lack of research into novel antibiotics and possible sources for them.  Nor will it delve into prevention of the ongoing misuse of antibiotics.  These topics have been well covered in other literature and it is more productive to now look at alternatives.  There are several areas of research concerning alternative therapies to antibiotic use.  CRISPR is a fascinating approach as the applications for CRISPR are far reaching and can be applied to other disorders and illnesses. This review focuses on the use of CRISPR-Cas9 as a therapy linked to antibiotic resistance but will not cover the other uses of CRISPR-Cas9.

(499 words)

References

• Bikard, D., Hatoum-Aslan, A., Mucida, D. and Marraffini, L. A. (2012) ‘CRISPR Interference Can Prevent Natural Transformation and Virulence Acquisition during In Vivo Bacterial Infection’,
  
  Cell Host & Microbe
  
  , Vol. 12, No. 2, pp. 177-186. [Online] Available at
  
  https://doi.org/10.1016/j.chom.2012.06.003
  
  (Accessed 29 Jun 19)
• de la Fuente-Nunez, C., Torres, M. D. T., Mojica, F. J. M. and Lu, T. K. (2017) ‘Next-generation precision antimicrobials: towards personalized treatment of infectious diseases’,
  
  Current Opinion in Microbiology
  
  , Vol. 37, pp. 95-102. [Online] Available at
  
  https://doi.org/10.1016/j.mib.2017.05.014
  
  (Accessed 27 Apr 19)

4. Chapter 1

1.1   Introduction – Background to topic

Since the introduction of penicillin to common use in the 1940s, when Alexander Fleming noted that the overuse of penicillin would lead to problems, there have been concerns about resistance to antibiotics.  By the late 1940’s resistance to

Staphylococcus aureus

had been noted in hospitals worldwide and was a concern to clinicians (Barber, 1947 in Podolsky, 2018).  In 1955 Lindsay Batten noted that “We may run clean out of effective ammunition and then how the bacteria and moulds will lord it” (Batten, 1955 in Podolsky, 2018).  Despite these warnings antibiotics were still over prescribed in general, and attempts to tackle the issue were seen at a local level but not addressed on a global platform (Podolsky, 2018).

Bacterial resistance to drugs causes 700,000 deaths worldwide annually and costs the NHS in the UK £180 million per year (House of Commons, 2018).  In 2011 the Chief Medical Officer’s report in the UK focused on the rising threat of antimicrobial resistance (AMR) to antibiotics and infections in which the author referred to AMR as ‘a ticking time bomb’ (Davies, S. 2011).  The report discussed the issue in detail and made specific recommendations to named organisations to aid in the battle against AMR.  Following this report, in 2013 the UK government set up a 5 year committee to tackle AMR which covered antibiotic use in humans, animals, and the environment.

1.2   Methodology

Following initial searches for papers on antibiotic resistance a more focused search on alternative therapies and their uses was utilised.  A mixture of primary research papers and reviews was used to inform the literature review on the use of CRISPR-Cas9 as an alternative therapy and its comparison to and discussion regarding other, alternative therapies.

1.3   Justification for topic and scope

Hospital workers are increasingly finding the need to look to alternatives to treat antibiotic resistant infections, particularly in immune comprised patients.

Chapter 2

2.1   Discuss the history, biology of and global impact of antibiotic resistance and the emergence of antibiotic resistance genes in microbes

There is evidence that humans have been using substances with antibiotic properties since 350-550 CE.  Studies of skeletal fragments from Sudanese Nubia showed tetracycline was present, indicating it was consumed by the individuals the bones belonged to (Nelson et al, 2010 in Aminov, 2010).  Further studies have shown that tetracycline was present in remains found in Egypt which dated to the late Roman period (Cook et al, 1989 in Aminov, 2010).  In addition to this, traditional Chinese medicine uses a variety of remedies which contain antimicrobial properties (Aminov, 2010).  Their presence in different locations and cultures indicate a conscious use to relieve symptoms of illness, even if the cause of the illness was unknown.  The value of these two studies involving tetracycline shows the same result achieved, from two time periods, using two methods.  The advantage of this is that each supports the other without necessarily being the aim of either.  The combination of these instances of substances with antimicrobial properties being used throughout history, and for long before the current overuse of antibiotics in recent history, may have been contributing to the rise of genes which confer antibiotic resistance in bacteria.  One example of this is

Klebsiella oxytoca

which has been developing a resistance to β-lactamase, although concomitantly to the bacteria expressing antibiotic resistance (ABR) (Fevre

et al.

, 2005).This suggests that perhaps ABR has been evolving for thousands of years and it is only the current overuse of antibiotics after the development in penicillin in 1928 that has sped up the evolution of the antibiotic phenotype.

There are six species of bacteria which exist and cause infections in both healthcare and non-healthcare settings worldwide and which concern researchers in terms of their development of antibiotic resistant genes.  These are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter species, shortened to the acronym ESKAPE (Rice, L. 2008).  The knowledge that the majority of ABR infections come from just six bacteria is an advantage to researchers and allows them to focus their attempts at a solution to the problem and pinpoint areas of weakness.  These bacteria can represent model organisms that can be used in the future should other organisms start to present the same problems, hopefully providing researchers a head start on how to proceed.

2.2   Briefly compare and contrast the alternative therapies available to treat infections caused by resistant bacteria

In recent years researchers have started to develop a number of alternatives to antibiotics to combat the growing problem of resistance including; bacterioricins, bacteriophages, faecal transplant, phage lysins, and probiotics (Brussow, 2017; de la Fuente-Nunez

et al.

, 2017).  Phage lysins attack bacterial cell walls and lyse Gram positive bacteria.  No resistance has yet been described but it has been shown to be effective against a number of infections including meningitis, pneumonia, sepsis, and pharyngitis in animal models as shown in a study by Pastagia et al (2013) in Brussow(2017).  However they do not diffuse away once they have been used and their action is not renewed so a way to remove the lysins is required.  A separate treatment which can be used which does not require a method of removal is faecal microbiota therapy (FMT), in which healthy microbiota is introduced into the gut of an infected individual, allowing the healthy microbiota to overtake and exclude the pathogenic bacteria (Ghosh et al., 2018).  This method has been shown to be effective in the treatment ofinfection caused

by Clostridium difficile, Salmonella,

and

Escherichia


coli

(Lahtinen et al., 2017)

.



Although some side effects were noted in this study they could not be attributed to the faecal transplant and it was ultimately concluded that the treatment was safe for those who are immune compromised.  However, more recently the US Food and Drug Administration (FDA) have announced their intention to halt FMT trials due to the death of an immune comprised patient who contracted an antibiotic resistant infection from FMT (Hou, 2019).

Chapter 3

3.1 Discuss the biology and use of bacteriophages as a delivery method of DNA into bacteria and the effectiveness of this approach

Bacteriophages, viruses which infect bacteria, are the most ubiquitous biological organism.  CRISPR-Cas9 can be used to introduce genes, mutations, and deletions in the genome into bacteriophages which could then go on to infect bacteria (Martel and Moineau, 2014).

3.2 Describe the use of the CRISPR-Cas system as an alternative therapy to bacterial infections and the modes of action employed in this approach

Small CRISPR RNA’s (crRNAs) are formed of sequences of spacers and repeats which have been processed within the cell.  These crRNAs rely on the relationship between the spacers in the CRISPR sequence and the bacteriophages.  These sequences can then produce an acquired immunity against any infection which would have been caused by the bacteriophage (Marraffini and Sontheimer, 2008).

Horizontal gene transfer between bacteria is a source of the spread of ABR.    This can be through transduction, transformation, or conjugation and can occur both within and between species.  Two bacteria which spread antibiotic resistant genes using conjugation for HGT are methicillin resistant

Staphylococcus aureus

and vancomycin resistant

Staphylococcus aureus

(MRSA and VRSA) (Marraffini and Sontheimer, 2008).  The resistant genes in the plasmid of one species of bacteria can spread to another species in this manner.  The Marraffini and Sontheimer study aimed to disrupt the delicate balance of sequence matching between CRISPR and cell RNA to prevent gene transfer.  This was achieved by creating a mutated conjugative plasmid by introducing nine silent mutations which changed the gene sequence, using the CRISPR sequence

spc1

and the

nes

gene conferring resistance.  There are several strengths to this study.  The clinically isolated

Staphylococcus epidermis,

RP62a,used in the study is a valid choice to study conjugative plasmid spread of genes due to its CRISPR sequence which is homologous to a spacer

(


spc1


)

found in the

nickase (nes)

gene.  This gene occurs in the conjugative plasmids of all sequenced

Staphylococci

allowing for the potential replication of the study with further

Staphylococci spp

to support the results in this study.  An attempt to support the results was also conducted by the authors.  Whilst initially they added mutations to the CRISPR sequence, in a follow up experiment the authors used a deletion to affect the sequence, and found results concurrent with the first experiment, and further were able to show that the

cas

sequence was required to alter the plasmid.  Obtaining multiple results which all support the aim of the paper allows it to act as a base point for other researchers who are looking at similar methods. Additionally, the research was focused on one specific method of transference of ABR genes.  An advantage of this is that the results are clear and can be more easily compared both within and across studies.

Chapter 4

4.1 Critically analyse the research evidence for the benefits and pitfalls of CRISP-Cas9 as a therapy

Although there are benefits to using CRISPR-Cas as an alternative therapy to bacterial infections there are also pitfalls and some further considerations before it can be used as a therapy.  The major disadvantage of this therapy is the lack of a clear way to administer this as a therapy and once it can be consistently shown to be effective the development of this should become a priority.  One possibility of this could be the introduction of bacteriophages to a person with an antibiotic resistant infection, or as a local application added to surfaces to disrupt colonies of bacteria and infect them with bacteria which aren’t resistant to antibacterials so that they can be cleaned more effectively.

Another disadvantage to the therapy is the scalability of it.  Currently, CRISPR-Cas therapies are tailored to an individual, making it costly and rendering it unsuitable for widespread applications on a large scale.  Currently, this means that only patients with severe infections would be treated and other treatments would still be required for the large majority of patients.

Ongoing mutations and evolution of bacteria mean that finding an alternative therapy is still a race.  Whilst the evidence from studies suggests that the removal, or introduction, of sections of the genome is successful care must be taken when altering the genome of bacteria in case unforeseen repercussions of this make the bacteria more virulent or result in mutations which benefit the bacteria.

4.2 Discuss the future of CRISPR-Cas9 and the opportunities for further research.

Chapter 5

Conclusion

The increase in the number and variety of studies concentrated on the problem of antibiotic resistance is an improvement on the lack of movement in research and healthcare communities in the past.   The spread of antibiotic resistant infections and the predicted deaths these will cause require immediate attention.  The uses of bacteriophages and CRISPR-Cas9 as alternative methods of treatment provide valuable areas of research which should be further explored.  Whilst CRISPR-Cas9 has advantages it also comes with disadvantages which must be overcome.

(1817 words)

References

• Aminov, R. I. (2010) ‘A brief history of the antibiotic era: lessons learned and challenges for the future’,
  
  Frontiers in Microbiology
  
  , Vol. 1. [Online] Available at https://doi.org/10.3389/fmicb.2010.00134 (Accessed 25 Mar 19)
• Bikard, D., Hatoum-Aslan, A., Mucida, D. and Marraffini, L. A. (2012) ‘CRISPR Interference Can Prevent Natural Transformation and Virulence Acquisition during In Vivo Bacterial Infection’,
  
  Cell Host & Microbe
  
  , Vol. 12 No. 2, pp. 177-186. [Online] Available at https://doi.org/10.1016/j.chom.2012.06.003 (Accessed 29 Jun 19)
• Brussow, H. (2017) ‘Infection therapy: the problem of drug resistance – and possible solutions’,
  
  Microbial Biotechnology
  
  , Vol. 10, No. 5, pp. 1041-1046. [Online] Available at https://doi.org/10.1111/1751-7915.12777 (Accessed 25 Mar 19)
• Davies, S. (2011) ‘ Infections and the rise of antimicrobial
• resistance’, Annual Report of the Chief Medical Officer, Vol 2 [Online] Available at https://www.gov.uk/government/publications/chief-medical-officer-annual-report-volume-2 ( Accessed 26 Mar 19)
• de la Fuente-Nunez, C., Torres, M. D. T., Mojica, F. J. M. and Lu, T. K. (2017) ‘Next-generation precision antimicrobials: towards personalized treatment of infectious diseases’,
  
  Current Opinion in Microbiology
  
  , 37, pp. 95-102. [Online] Available at https://doi.org/10.1016/j.mib.2017.05.014 (Accessed 27 Apr 19)
• Fevre, C., Jbel, M., Passet, V., Weill, F. X., Grimont, P. A. D. and Brisse, S. (2005) ‘Six groups of the OXY beta-lactamase evolved over millions of years in Klebsiella oxytoca’,
  
  Antimicrobial Agents and Chemotherapy
  
  , Vol. 49, No. 8, pp. 3453-3462. [Online] Available at https://doi.org/10.1128/aac.49.8.3453-3462.2005 (Accessed 25 Jun 19)
• Hou, C. (2019) ‘FDA Suspends Clinical Trials Involving Fecal Transplants’,
  
  The Scientist,
  
  [Online] Available at https://www.the-scientist.com/news-opinion/fda-suspends-clinical-trials-involving-fecal-transplants-66009?utm_content=94952047&utm_medium=social&utm_source=facebook&hss_channel=fbp-242730579188418&fbclid=IwAR3F88E1uRna-B7ge8d7G6vwdnw5sXHPAwu96tEYKFfaA_9S-1tuV_D1I7M (Accessed 26 Jun 2019)
• House of Commons (2018) ‘Antimicrobial Resistance, Health and Social Care Commitee [Online] Available at
  
  https://publications.parliament.uk/pa/cm201719/cmselect/cmhealth/962/962.pdf
  
  (Accessed 25 Jun 19)
• Lahtinen, P., Mattila, E., Anttila, V. J., Tillonen, J., Teittinen, M., Nevalainen, P., Salminen, S., Satokari, R. and Arkkila, P. (2017) ‘Faecal microbiota transplantation in patients with Clostridium difficile and significant comorbidities as well as in patients with new indications: A case series’,
  
  World Journal of Gastroenterology
  
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• Marraffini, L. A. and Sontheimer, E. J. (2008) ‘CRISPR Interference Limits Horizontal Gene Transfer in Staphylococci by Targeting DNA’,
  
  Science
  
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• Martel, B. and Moineau, S. (2014) ‘CRISPR-Cas: an efficient tool for genome engineering of virulent bacteriophages’,
  
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Does the use of Palliative Care and comfort measures during End-of-Life provide the patient a more peaceful death experience?

Annotations

Annotations marked with an asterisk indicate studies included in a systematic review

Waldrop, D.P., & Kirkendall, A.M. (2009). Comfort measures: A qualitative study of nursing home-based end-of-life care. Journal of Palliative Care Medicine, 12(8), 719-724.

Waldrop and Kirkendall (2009) surveyed employees from a 120-bed suburban nonprofit nursing home to explore how their staff recognized a dying patient and identified standards of care which would be put into place once palliative care has been initiated. Using a qualitative method to gather data, 42 employees were interviewed which included nurses, chaplains, social workers, nursing assistants, housekeepers, and administrators to provide multiple perspectives on the dying experience. The survey was done in the form of a 30-minute interview in a quiet location of the nursing home away from the nursing unit (Waldrop & Kirkensall, 2009). An affiliated research assistant or investigator whom has had training in conducting interviews and qualitative data analysis conducted it. They asked the employees open-ended and objective questions about frequency and standards of care for dying patients and their families. “All interviews were audio taped, transcribed by a professional transcriptionist, and labeled with a letter number combination (e.g., N[urse]-1). The transcripts were entered into Atlas ti software for data organization and management”(Waldrop & Kirkensall, 2009). The survey identified physical, behavioral, and social factors as the three main indicators of impending death. Physical indicators included altered breathing patterns (including apnea), anorexia, or increase in pain; behavioral indicators included mood changes and diminished activity level and social indicators sometimes included withdrawal from interaction with staff or family (Waldrop & Kirkendall, 2009). During the survey the staff explained that Comfort care is initiated when patients began to exhibit these signs. At this nursing home standard order sets were not used and comfort care measures were described as being very patient individualized and holistic. Comfort care includes an interrelationship of symptom management, family care, interpersonal relationships, and interdisciplinary cooperation in which each member of the healthcare team participates in the care of the patient, according to their scope of practice (Waldrop & Kirkendall, 2009).

The survey revealed that health care employees deliver comfort care in different ways and it identified the need for more comparison studies in other nursing homes to explore standards of care in other facilities because this was just one study of one nursing home. By further comparing nursing homes which use different models of care comfort care standards and or improvements can be made. This survey was conducted in a nursing home setting but its results reflect on hospital end-of-life care. At the present time the standard of care for dying patients in a hospital setting consists of pre-printed order sets which are not individualized to the specific needs of the patient. This study promotes use of the holistic, individualized care approach to ensure a more satisfying and comforting dying experience.

Level of evidence: VI Single descriptive qualitative/physiologic study

Jarabek, B.R., Cha, S.S., Ruegg, S.R., Moynihan, T.J., & McDonald, F.S. (2008). Use of a palliative care order set to improve resident comfort with symptom management in palliative care. Palliative Medicine, 22, 343-349.

Jarabek, Cha, Ruegg, Moynihan, & McDonald, (2008) began a study within the Internal Medicine Residency Program at Mayo Clinic in Rochester, Minnesota hypothesized that standard palliative order sets within a hospital setting would enhance physician comfort with managing 4 aspects of end-of-life care: pain, secretions, agitation, and dyspnea. A 5-question, pre-intervention web-based survey regarding physician comfort in diverse aspects of palliative care was given to 144 internal medicine resident physicians before the release of the palliative order set, which would later be used within the hospital. Each question included a 5-item Likert response scale, ranging from 1, “very comfortable” to 5, “very uncomfortable”(Larabek et al., 2008). Three months later an educational email was sent to all house staff and faculty addressing end-of life-care along with the initiation of the order set, which consisted of physical ailment provisions. Another 3 months was spent allowing staff to use and or work with the order sets at which point a post-intervention survey was performed. Results of the post-intervention survey were that 88% had utilized the palliative order sets and 63% stated that they felt increasingly comfortable with palliative care (Jarabek et al., 2008). There was an overall 10% increase in resident comfort regarding the 4 aspects of palliative care with the initiation of order sets, but no change in social or communication-related comfort (Jarabek et al., 2008). The survey concluded that palliative order sets can increase physician comfort in providing care to patients during end-of-life, but it also revealed that the order sets do not address the psychosocial needs of the patient when providing comfort care. Although physicians find comfort in having order sets as guidelines for end-of-life care, they are only guidelines and open communication needs to be initiated between the health care team and the patient to ensure all the comfort care needs of the patient and family are met in a holistic way so that they may have a peaceful dying experience.

Level of evidence:

Teno, J.M., Clarridge, B.R., Casey, V., Welch, L.C., Wetle, T., Shield, R., & Mor, V. (2004). Family perspectives on end-of-life care at the last place of care. Journal of the American Medical Association, 291(1), 88-93.

Teno, clarridge, casey, welchl wetle,shield, mor (2004) evaluated 1578 adult patients with different, chronic illnesses end of life experiences by surveying the decedent’s loved ones and determining whether their perspectives on quality end-of-life care were influenced by the environment where the patient spent their last 48 hours of life. A survey was devised from a conceptual model for patient-focused, family-centered medical care and the calculation of scores and psychometrics of the measures were taken from an online tool formulated by Brown University. Within 9 to 15 months from the time of death a close family member or informant whom was listed on the death certificate was surveyed and was asked about the quality of care their loved one received during their last 48 hours of life. Five different domains were used in the survey, including whether healthcare workers provided patient physical comfort and emotional support, supported collaborative decision-making with the physician, treated the patient with respect, attended to family needs, and provided coordinated care with other healthcare workers or facilities (Teno., et al. 2004).

Teno et al. (2004) concluded that 69% of the decedents site of death and last place to receive care was in a hospital or nursing home setting, 31% home, 36% without nursing service, 12% home nursing, and 52% home hospice. The survey showed that family perceptions of the quality of care were different according to where their loved one last received care. Families of patients who were in nursing homes or had home health had a higher rate of unmet needs for pain (Teno., et al. 2004). Over half of the families in hospital or nursing home settings reported unmet emotional needs. In addition, 70% of families receiving home health care reported inadequate emotional support in comparison to 35% in families who utilized home hospice care. Patient and family respect was also a concern to families and varied in different settings. Only 68% of nursing home residents’ families felt they had been treated with respect and consideration compared to the 96% of families receiving hospice care (Teno et al., 2004). Survey participants felt that physical symptom management was adequately managed so it was comparably equal throughout all patient settings. Although families did not experience a difference in pain or dyspnea management in comparison to other nursing services families who used hospice services overall, 71% reported “excellent” care (Teno et al., 2004).

Kolcaba, K.Y., & Steiner, R. (2004). Efficacy of hand massage for enhancing the comfort of hospice patients. Journal of Hospice and Palliative Nursing, 6(2), 91-102.

Kolcaba, Dowd, Steiner, and Mitzel (2004) identified the need for comforting interventions for patients at end of life that are simple, easy to learn and administer, and require minimal effort on behalf of the patient. Bilateral hand massage is a good intervention because it is noninvasive, easy to do, does not take long, and relies on caring/healing touch( Kolcaba., et al. 2004). The purpose of their study was to determine empirically if a bilateral hand massage provided to patients near end of life twice per week for 3 weeks was associated with higher levels of comfort and less symptom distress.

31 adult hospice patients from 2 hospice agencies participated in the study. Each patient was English-speaking and expected to remain alert and oriented for the duration of the trial, 13 months. “Data collectors who were unknown to the patients called the homes of the patients, explained the study, and then scheduled an appointment for a research visit. Data was collected at the patients homes and at the hospice centers”(Kolcaba., et al. 2004). After informed consent, participants were randomly divided into the treatment group (with 16 patients) and the comparison group (with 15 patients). All participants were asked to complete a modified General Comfort Questionnaire (GCQ), tailored for end-of-life patients, once a week for 3 weeks. After completing the questionnaire each week, the treatment group then received the hand massage intervention twice a week for 3 weeks. The comparison group received the intervention once at the end of the study period.

The study concluded no significant difference between the treatment and comparison groups in regard to enhanced comfort or decreased symptom distress over time (Kolcaba et al., 2004). However, comfort did increase some in the treatment group even as the patient approached death. The study also revealed that the hand massage seemed to allow more time for therapeutic or face to face communication allowing the patients to talk about how they feel and their feelings on transitioning to death, and patients receiving the intervention reported it to be a personalized experience something they could engage in that feels good, and family members were appreciative of the care and attention their loved one was getting (Kolcaba et al., 2004). Because this intervention is easy to learn and requires minimal time for the caregiver to do and minimal effort for the patient it is an excellent intervention that can even be taught to the family. This study identifies interventions that can be used within the hospital setting and any other setting to enhance comfort during end-of-life. Nurses and family members can use this intervention to increase communication by using caring touch, which provide psychosocial care and therefore holistic comfort for the patient.

Bakitas, M., Lyons, K. D., Hegel, M. T., Balan, S., Brokaw, F. C., Seville, J., Hull, J. G., Li, Z., Tosteson, T. D., Byock, I. R., Ahles, T. A., (2009). Effects of a palliative care intervention on clinical outcomes in patients with advanced cancer. The Journal of the American Medical Association. 302 (7): 741-749.

Bakitas, Lyons, Hegel, Balan, Brokaw, Seville, hull, Li, Tosteson, Byock, Ahles, (2009) using project ENABLE combined with a nurse-led intervention with ongoing assessment, coaching, symptom management, crisis prevetion, and timely referral to palliative care and hospices hypothesize that patients newly diagnosed with advanced cancer if exposed to this intervention right away would become informed, active participants in their care, and would experience an improved quality of life, mood, and have better symptom relief. “The study protocol and data and safety monitoring board plan were approved by the institutional review boards of the Norris Cotton Cancer Center and Dartmouth College in Lebanon, New Hampshire, and the Veterans Administration (VA) medical center in White River Junction, Vermont. All patient and caregiver participants signed a document confirming their informed consent.”(Bakitas., et al (2009). Participants completed baseline questionnaires when they were enrolled and then completed a follow-up one month later. Using a stratified randomization scheme patients and their caregivers were randomly assigned to the interventions or usual care group. One of 2 advanced practice nurses with palliative care experience conducted 4 structured educational problem solving sessions first one lasting 41 minutes and sessions 2 through 4 approx 30 minutes each and at least monthly telephone follow-up sessions until the participant died or the study ended (Bakitas., et al.2009) The advanced practice nurse began all contacts with an initial assessment by administering the Distress Thermometer, an 11-point rating scale recommended by the National Comprehensive Cancer Network guidelines. It identifies sources of distress in the 5 areas of practical problems physical problems, family problems, spiritual, emotional problems or religious concerns. If distress intensity was higher than 3, the advanced practice nurses then identifies the sources of distress and checks to see if the participant would like to problem/solve to take care of their issue. The nurse then covers the assigned module for that session. The participants’ clinical teams are responsible for all medical decisions and inpatient care management, however the advanced practice nurse was readily available by telephone for the participants and they could also facilitate ancillary resources. The participants also were able to participate in group shared medical appointments (SMAs), which are led by certified palliative care physicians. The usual care participants were allowed to use all oncology and supportive services without restriction. Follow-up questionnaires were mailed every 3 months until the patient died or study completion in December 31, 2007. Quality of Life was measured with a 46-item tool called the Functional Assessment of Chronic Illness Therapy for Palliative Care. It measures the participants’ physical, social, emotional, and functional well being along with the concerns of a person whom has a life-threatening illness. Of 1222 screened, 681 were eligible and were approached and 322 were enrolled (47% participation rate). There were a total of 134 participants in the usual care group and 145 participants in the intervention group. ” ‘A systematic review of specialized palliative care identified 22 trials (16 from the United States) between 1984-2007 with a median sample size of 204, half exclusively with cancer patients. ‘”There was lack of evidence due to contamination, adherence, and recruitment etc. The trial addressed these issues and contributed to the increasing evidence that palliative care may improve quality of life and mood at the end of life.” In our study, intervention participants’ higher quality of life and lower depressed mood may be attributed to improved psychosocial and emotional well being.” Mood is a determinant of the experience of quality of life and suffering despite a mounting burden of physical symptoms”(Bakitas., et al. 2009). “However, while patients in the intervention group had improvement in these outcomes, we conservatively planned our original target trial enrollment of 400 based on a significance level of .01.’ Statistical inferences based on this stringent critical value would lead to the conclusion that there were no statistically significant differences between groups in quality of life or mood”(Bakitas., et al. 2009). The study concluded that compared with participants receiving usual oncology care those receiving a nurse-led, palliative care-focused interventions that takes care of the patient holistically provided at the same time with oncology care had higher scores for quality of life and mood, but did not have improvements in symptom intensity scores or reduced days in the hospital (Bakitas., et al. 2009).

Level of evidence-

Summary

The research presented reveals while palliative care order sets provide a helpful guideline or tool which reassures health care providers in giving consistent good quality care, patients care needs should be assessed and individualized orders and interventions should be implemented to ensure a peaceful and comforting dying experience. Hospice care settings have been shown to provide excellent holistic care for dying patients and they have also been shown to show compassion to the family as well. The comfort interventions from these facilities can be modified for application in the hospital for use in the acute care setting. Holistic comfort care interventions include hand massage, music therapy, or the utilization of a visual analog scale” the faces” to measure comfort. These are some of the ways hospitals can utilize the findings from this research into daily practice to ensure quality holistic patient comfort is achieved and ultimately a peaceful death.

The motive of this assignment is to discuss how law, ethics and elements of professional practice have influenced care and professional judgements within this case study. A critical analysis approach will be adapted with the main focus on ethical principles and also reflecting on elements of law and professional practices. The main source of the care intervention will be focusing on maintaining confidentiality in relation to patient’s personal information, and the handling of patient’s information in a way that does not breach confidentiality. Within the context inter-professional collaboration and how the impact a different professional perspective may bring will be explored. The privacy of patients’ will be respected, pseudonym will be used to give a fictitious name to protect the identities of those involved, this is acknowledgement with the nursing and midwifery council (NMC, 2018). The Human Rights Act (1998) also states to respect people’s rights to privacy and personal information. In this case study the patient will be identified as Elsie.

This is a case presentation of a 76-year-old lady Elsie, who visited day case surgery for an elective procedure to have a corticosteroid injection in to her joints due to an ongoing back problem. She is a widow who lives alone. She was a factory worker and has been retired for the last 12 years. She has a medical history of C.O.P.D. and arthritis. COPD foundation (N.D) details Chronic Obstructive Pulmonary Disease (COPD) is used to describe progressive lung diseases which are recognised by accumulative breathlessness. Arthritis foundation (N.D) describes arthritis as an informal way of referring to joint pain or joint disease. She is independent with abilities to do activities in her daily life but is occasionally limited by her long-term condition arthritis and is currently cared for by the pain management clinic for the last few months.

To begin Elsie’s care experience on a surgical ward she was introduced to the author, the author was supervised by a trained nurse. On admission the author went over Elsie’s medical paperwork which consisted of her personal details, this was done by carrying confirmation of consent, identity checks and medical history before her surgery. The author also took Elsie’s clinical observation pre and post operatively.

Saunders (2016) expresses in the health care setting, that confidentiality means restricting the circulation of patient’s information with the agreement to protect information shared between a patient and a provider, unless explicit permission is given to share that information. General medical council (GMC) (2018) for doctors state it is a crucial part in confidentiality to preserve trust and it is also a matter of legal and ethical safeguards. In support of this Winters (2013) states the duty to safeguard patients confidentiality and information is a statutory and ethical feature all healthcare professionals should have. In the circumstance of Elsie’s care the author had to use critical decision making and have a understanding how actions can have an negative and positive effect on Elsie’s physical and mental welfare. With this in mind it is advised by the NMC (2018) to draw special care to encouraging well-being, and averting ill health. It is important for author to have an understanding of these principles and be able to apply them in to practice.

Buka (2015) writes ethics is based on classifying what is deemed in human behaviour as righteous and unrighteous. Adjoining on to Buka (2015) an interpretation from Griffith and Tengnah (2017) suggest ethics as the study of what is acceptable and unacceptable in human nature in regards to the way they conduct themselves. Deontology theories of ethics insist that the means must justify the end (Barrow and Khandhar, 2019). It states that some rights must not be violated even if it may produce the greatest overall good. Utilitarianism, on the other hand is an ethical theory of moral principles which states that the moral act is one, which produces the greatest amount of benefits over harms for everyone involved (Gallagher and Hodge, 2012).Historically the approach that utilitarian emphasis is the premise of doing things based on the greater good for the greater mass of people (Edwards, 1996).In other words it means to overall diminish suffering and upsurge happiness for the greatest number of people, an example of utilitarian reasoning in the case of Elsie, would consist of letting Elsie suffer to benefit 5 patients, so if having to choose minimizing the loss of life would be considered .

The standard theoretical framework which is used to analyse ethical situations in nursing practice is the biomedical principles of ethics by Beauchamp and Childress (2013). Almost all episodes of care encompasses of the four ethical principles: autonomy, non-maleficence, beneficence and justice.

The concept of autonomy is widely understood to mean, the patient having the rights to self-govern with the ability to constitute this in relation to their own best interests (Entwistle

et al

., 2010).The word autonomy symbolises having the freedom of choice regarding situations about one’s life (Stacey

et al

., 2017).Throughout the care episode the author encouraged Elsie to participate in her own decision making and promoted Elsie’s rights to independence. The NMC (2018) have encouraged respect to be given to those who are in receipt of care, enabling them to have input into decisions about their own health and wellbeing. Autonomy was applied in relation to respecting Elsie privacy to disclose sensitive information shared to the medical staff, this decision was ultimately respected and also included the right to choose who should have access to her private information. Rebecca (2009) states promoting autonomy and independence underpin many tactics to cultivating the quality of nursing care for patients in the healthcare setting. As Rebecca (2009) raises the importance of promoting independence she neglects to realize healthcare professionals such as nurses may often fail to identify indirect violations of patient’s autonomy. Burkhardt (2014) hypotheses nurses misleadingly have a perception that patients hold the same goals and principles as their own personal ones. This way of thinking may compel them to deliver care consistent with their own values and goals. Supplementing this in professional guidance the NMC (2018) advises nurses to avoid making assumptions and identify diversity and personal preferences.

Beneficence and non-maleficence can sometimes be viewed together however, the difference between them is that beneficence for a healthcare professional is to actively act in way that benefits patients (Gillion, 2015).Beauchamp & Childress (2013) state the principle of beneficence also upholds that we must prevent evil and maltreatment. Whereas the principle of non-maleficence is to do no harm such harm whilst doing beneficial acts (Burkhardt, 2014). Beneficence is seen to involve a protection of duty in a way that benefits the patient (Hendrick, 2011). Coyne and Gallagher (2011) identifies that issues can arise within healthcare situations involving patients, particularly regarding principles of beneficence and autonomy. In the authors view nurses must follow their respected professional codes as well as bearing in mind what is most beneficial for the patient, whilst respecting the wishes of the family members which might not be steering towards the same decision as the healthcare professional. NMC (2018) state to balance care treatment which is tailored around the person’s rights and wishes to accept or refuse care, nurses must always make sure they promote the most advisable treatment which would benefit the patient. Following this guidance would entail sharing Elsie’s personal data with healthcare professionals this is only acceptable if Elsie’s safety was compromised, as breaching her confidentiality would be overruled to prevent her from harm that could be inflicted (GMC,2018).

Non maleficence as already stated is said to be not to harm, this obliges nurses from imposing a risk of harm to others (Beauchamp and Childress, 2013). In regards to harm the NMC (2018) highlight to respond immediately if someone in care has suffered potential or actual harm. The guidance the author took in to consideration from the Royal College of Nursing (RCN) (2016) in relation to sharing Elsie’s information to other healthcare professionals around the bay was to be mindful of not been overheard. Protecting Elsie’s confidentiality consisted of using effective communication methods which were used by not deliberately sharing Elsie’s details to a person of no concern. Purposely shouting Elsie’s information out loud would put her at risk and breach her privacy. Jonsen (2003) in his earliest works listed medical non-maleficence into four categories: firstly dedicate themselves to well-being (not harm) of patients, secondly provide adequate care, thirdly properly assess the situation, that is the risk/benefit analysis; and fourthly make proper detriment benefit assessments.

Justice is related to fair treatment and care that is equitable to meet everyone’s needs and care that will promote equality (Crawshaw et al, 2012).The principle of justice could also be described by Alperovitch

et al

. (2009) as a moral obligation that is linked to fairness, entitlement and equality. Elsie’s was treated fairly and was not discriminated in any way in line with her treatment, at times she had more assistance then others in her care provision to make her care more equitable to meet her needs. With regards to equality in a healthcare environment some healthcare professionals show acts of favoritism to certain individuals over others. According to Cropanzano and Stein (2009) behaviours expressing stigmatisation and acting in a discriminative and prejudice nature can be seen to categorize people into groups which makes individuals feel devalued on certain characteristics. The NMC (2018) have advised nurses to act with the utmost honesty and integrity, and to also treat patients without discrimination in anyway.

Aston, McGown and Wakefield (2010) articulate a professional such as nurses has undertaken intensive theory and practical based training in the field which they practice, this enables them as professionals to make legal and ethical decisions regarding issues in nursing care. The NMC (2018) code was constructed around the laws set in the UK, it consists of ethical, professional and legal principles. The NMC (2018) code of practice must be adhered to by all nurses. The Code of the NMC (2018) states as a professional in their role, nurses must treat every patient who is under their care to be treated with integrity and also comply to the laws set in the country in which they practice. There are different healthcare professional within the healthcare settings such as psychologists and psychiatrists, they all have different governing bodies that they follow. In professional standards relating to confidentiality the NMC (2018) state that nurses have a duty of care by professional practice, to protect patient confidentiality in any care intervention which encompasses having a duty to inform patients of how information regarding them is shared appropriately. Elsie’s right to privacy was respected in all aspects of her care. The author made sure that Elsie’s was informed about how and why her information was used and shared in relation to her procedure this was done by following professional guidelines of the NMC (2018). Information was shared in a professional manner between the author and multidisciplinary team regarding all aspect of Elsie care. NMC (2018) had advised nurses to share information with patients and their next of kin or those who are legally bound to know.

Griffith and Tengnah (2017)narrowed down and selected certain areas of the law which are vitally important for nurses to understand, they consist of a individuals human rights, equality, safeguarding, accountability, confidentiality and record keeping. Types of legislative process In the UK there are essentially three ways in which new laws come into being: through Acts of Parliament (statute), by secondary legislation and by common law (case law). There are acts which are brought to bear on the work of a nurse, these being the Mental Capacity Act (MCA) 2005 and the Human Rights Act 1998.

The MCA (2005) is the ruling which helps us understand the legal concept of capacity. The principle of consent is an important part of ethics law and professional requirement, it consist of informing Elsie regarding her rights and providing an explanation of the care intervention and potential risks and benefits (Nijhawan

et al

., 2013). For Elsie to be able to consent to any treatment she must be deemed to have capacity. The part of law that deals with capacity to consent is the MCA (2005). In the care episode consent was established before any care intervention was taken between the author and multidisciplinary team in relation to Elsie care. The GMC (2018) have various procedures on informing the patient before gaining consent, stating if sufficient information is not relayed over to a patient to make a informed decision regarding their treatment then the premises of consent is not valid.

Article 8 of The Human Rights Act (1998), enforces an individual’s right to privacy in regards to their daily life, family life and correspondence. This also relates to the sharing of Elsie’s personal information, this right means that professionals and local authorities must respect Elsie’s privacy unless it is on legal grounds, this is relative to public interest and public safety. (Lynch, 2016). Elsie’s disclosure to privacy can be overridden if its not seen to be in the public’s best interests.

In handling Elsie’s medical records duty of care was to ensure her medical records were not easy accessible to the general public or in a attainable place. It is was also important that all her records were kept confidential.The NMC (2018) require nurses to withhold responsibilities when handling patients data and storing medical records of patients securely, this also reflects the rights of the individual under the General Data Protection Regulation (GDPR, 2018). GDPR (2018) requires everyone to be responsible when using personal data, whilst making sure all information is used lawful and transparent.

When corresponding with the multidisciplinary team it is vitally important that the outcomes is to provide effective and safe care (van Veen-Berkx

et al

.,2015).During Elsie care experience there were various healthcare professionals involved ranging from student nurses, trained nurses, health carers and consultants.It is of vital importance that healthcare professionals work together collectively adopting practices of great understanding and effective communication (Burzotta and Hoble, 2011). Webb (2011) in a similar fashion state that healthcare professionals are encouraged to work together whilst cooperating and sharing various skills, healthcare professionals should also respect each other and be able to voice their own opinions. Care experiences which do not flow properly due to miscommunication will not meet holistic needs of the patient ,this is why team working should be the ultimate goal (Thurston, 2013). Burzotta and Hoble (2011) determine all inter professional team members all collectively contribute to vital information sharing which fundamentally make a strong team.The NMC Code (2018) encourages nurses to embrace skills which other healthcare professional bring, confirming and reassuring practices to ensure care is given in confidence .

In conclusion a healthcare professional must abide to professional ,legal and ethical guidelines, it is very important that nurses are educated in such areas as decision made may have a vast impact on patients, whether that be a professional or a personal decision (Gallagher and Hodge,2012).Regarding Elsie’s care it is essential that legal, ethical and professional practices conjoined to deliver a quality of care that is satisfactory. The GMC (2018) prides itself on the value of excellent and high quality care. The NMC (2015) also embed the same values of delivering a high standard of care which beneficially puts the patient at the centre of their care, by considering their best interest these professional aspects drive the decision making in all care episodes.

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