Evidence-Based Nursing Research

Introduction

Ventilator-Associated Pneumonia (VAP) is a subcategory of hospital-gotten pneumonia that affects patients under mechanical ventilation through a tracheostomy or endotracheal tube for at least forty-eight to seventy-two hours. This form of pneumonia affects nine to twenty-seven percent of patients in the ICUs. In the USA, the expenditure is two billion dollars yearly and nearly thirty thousand to forty thousand dollars per case

(Berry et al. 2017).

The rate of mortality for VAP varies from twenty to seventy percent. VAP intensifies the duration of hospital stay and mechanical ventilation. It is also liable or for fifty percent of the antibiotics recommended in the ICUs.

The most significant method in VAP development is the unceasing micro-aspiration of oropharyngeal colonization into the lower respiratory tract. A day after a patient’s entry to the ICU, common oropharyngeal flora adjusts into gram-negative pathogens that elevate dental plaque. Plaques are conducive environments for the accumulation and growth of pathogens. Moreover, the tracheal tube may function as a channel for the oral cavity pathogens of the oral cavity to the lungs

(Woodrow. 2011).

Numerous research has demonstrated an association between respiratory pathogens and dental plaque colonization. Luckily, the incidence of VAP IS minimized through improving prevention methods and by identifying the risk factors. Currently, the rate of mortality of VAP has been projected at about nine to thirteen percent.

My PICO

Population: Adult population in the Intensive Care Unit with a mechanical ventilator.

Intervention: Oral topical decontamination

Comparison: No standard oral care or no solution.

Outcome: Minimize ventilated associated pneumonia among adult ICU patients with a mechanical ventilator.

Answerable Question

Answerable question: What is the efficacy of oral rinse with 0.2 percent and 2 percent chlorhexidine on oropharyngeal in minimizing the prevalence of ventilator related pneumonia?

The answerable question was developed by first identifying the population who are adult patients in ICU with a mechanical ventilator. Secondly, I came up with the intervention that is to minimize the likelihood of contracting pneumonia among adult patients with a mechanical ventilator. Then thirdly, a comparison is made, which is then followed by the outcome of the intervention. Finally, an answerable question is formulated that comprises of the above-stated parts.

Literature

Ventilator-associated pneumonia progresses to cause difficulties to the cause of eight to twenty-eight percent of patients getting mechanical ventilation. In divergence to infections of more regularly engaged organs (for instance skin and urinary tract), for which mortality is little, varying from one to four percent, the rate of mortality for VAP varies from twenty-four to fifty percent and can get to seventy-six percent when lung infection is caused by some high-risk pathogens or in some specific settings. The leading organisms liable for infection are Pseudomonas aeruginosa, Staphylococcus aureus, and Enterobacteriaceae, though etiologic agents extensively vary according to the patient’s population in an intensive care unit, prior antimicrobial therapy, and duration of hospital stay. Since suitable antimicrobial therapy of a patient with VAP substantially enhances results, more accurate selection of microbial agents and rapid identification of infected patients represent crucial clinical targets. Notwithstanding the major developments in strategies for the management of patients who are dependent on a ventilator and the regular utilization of useful methods to clean respiratory tools, VAP progresses to set hurdles to the course of eight to twenty-eight percent of the patients getting mechanical ventilation. Pneumonia rates are noticeably greater among hospitalized patients in the ICU contrasted with those in hospital wards, and the threat of pneumonia is intensified by three to tenfold for the patient who is intubated and is getting mechanical ventilation.

The current review is based on an assessment of the literature, chosen through a computerized MEDLINE search from the year 1980 to the year 2001. Consensus statements, review articles, and the references cited were also contemplated in this attempt to revise our present knowledge on the diagnosis, epidemiology, and treatment of VAP. Since the Hospital Infection Practice Advisory Committee of the Centers for Disease Prevention and Control published up-to-date and extensive suggestions for the deterrence of nosocomial pneumonia in 1997 and other comprehensive reviews are also available.

Correct data on VAP epidemiology are constrained by the lack of harmonized criteria for its diagnosis. Theoretically, VAP is described as the inflammation of the lung parenchyma instigated by agents that are infectious that are incubating or absent at the time the MV began. Notwithstanding the clearness of this conception, the last 3 decades have seen the advent of several definitions of operation, which none is accepted universally. In focal areas of the lobe, pneumonia may fail to be seen, microbiologic research may be negative notwithstanding the existence of inflammation in the lung and practitioners may differ concerning the discoveries. The nonexistence of a ‘gold standard’ remains to bring disagreements concerning the relevance and adequacy of many studies in this field.

Persistent (greater than forty-eight hours) MV is the most significant element linked with nosocomial pneumonia. Nevertheless, VAP may take place with the first forty-eight hours after intubation. Since the princeps study by coworkers and Langer, it is normal to differentiate early on-onset VAP that takes place during the first four days of MV, from late-onset VAP, that advances 5 or more days after the start of MV. Not only are the pathogens that cause the disease usually different but the prognosis is better in early-onset than late-onset VAP and the disease is normally less severe.

Wide-Scale 1-point prevalence research of pneumonia beginning in the intensive care unit was undertaken on April 29, 1992, in one thousand four thousand and seventeen intensive care units. Accumulation of ten thousand and thirty-eight patients was examined: two thousand and sixty-four (twenty-one percent) had intensive care unit gotten infections, including pneumonia in nine hundred and sixty-seven (forty-seven percent) patients, for a general nosocomial pneumonia prevalence of ten percent. In that research, regression analysis for the logistic recognized MV as one of the seven factors of risk for the intensive care unit –acquired infections. Another wide-scale research, undertaken in one hundred and seven intensive care units showed a crude rate of pneumonia of nine percent, in that research, Mechanical ventilator was linked with a three-fold greater threat of advancing VIP than that examined by for non-ventilated patients. On the grounds of their assessments of general rates of nosocomial pneumonia, Roup and Cross-reported ten-fold greater occurrences

Critical Appraisal

The current randomized clinical trial was intended to implement and design a protocol for oral care and compare the results of two diverse concentrations of chlorhexidine on minimizing VAP and oropharyngeal colonization among hospitalized patients in the intensive care units of Shahid Rajaee and Nemazee hospitals. This research was registered in the Iranian Registry of Clinical Trials and commended by the Ethics Committee of Shiraz University of Medical Sciences. The criteria of inclusion of the research comprised patients aged eighteen years or above, being under mechanical ventilation for at least forty-eight hours and not suffering from inflammation of the oral mucosa or trauma to the mouth. Others include not having a history of allergy to chlorhexidine, not suffering from burn damages, not having immune disorders caused by illness or medication not being pregnant, not suffering from burn damages and being admitted to the ICU for the first time. Admission of patients was because of surgery, trauma, medical, neurological, or neurosurgical challenges. The projected occurrence of VAP in the ICUs was about fifteen to twenty-two per one thousand days of mechanical ventilation. Primarily, written enlightened consent was gotten from every patient’s legal or relative guardian (due to the patient’s consciousness that is low level). The patients were then erratically assigned to two groups of 0.2 percent and 0.2 percent chlorhexidine based on a computer-generated table of randomization. Patients, who had noticeable aspiration, were identified with thrombocytopenia and likelihood of bleeding because of oral care, or had globally normalized ratios above two were exempted from the research.

The occurrence of VAP occurrence of VAP was examined by Clinical Pneumonia Infection Score (CPIS). We also contemplate the adjustment in antibiotic therapy by intensivists at ICUs. The Beck of mucosal-plaque and oral assessment scale was utilized to assess the oral cavity status. Moreover, tracheal and oropharyngeal colonization were examined by semi-quantitative culture APACHE IV was utilized to examine the gravity of the disease during the first twenty-four-hour of admission in Intensive Care Units. This trial addressed a focused issue of oral care ventilated patients in intensive care units. The assignment of patients to treatments was randomized. The practitioners conducted random patient treatment and the allocation sequence was not hidden from patients and researchers. Health workers, patients, and study personnel were not blind to treatment. All the groups were involved in the treatment of the disease. In the beginning, the researcher looked at all guidelines and protocols associated with oral care from 2003 onward. Then, numerous meetings of the team were held with an intensivist, a specialist in microbiology, two faculty members from the School of Nursing, a periodontal disease specialist, an infectious disease specialist, two ICU nurses, a clinical pharmacist, and ICU and infection control supervisors.

In the subsequent stage, a dental assistant trained the researcher in the utilization of the oral assessment tool. The researcher for five patients and in the presence of the assistant upon arrival undertook oral care and oral assessment. The patient’s information on demography was gathered through interviews with the patient’s medical and families’ records. The researcher finalized the checklist based on CPIS by examining the flowsheets of the patient with the collaboration. In instances where the accumulated CPIS monia, the patient’s outcomes of the tracheal culture were assessed, in case of positive culture outcomes, the patient was exempted from the research. non-intubated patients allowed in the intensive care unit who required mechanical and intubation ventilation for more than forty-eight were also researched. As soon as admission to the intensive care unit, a culture of the oropharyngeal secretions was taken after, suction o the throat utilizing a sterile applicator that was taken from the laboratory. A tracheal tube culture was also obtained through the aspiration of the tracheal tube and the BAL tube. The two samples were conserved in normal saline and sent to the laboratory. The samples of the tracheal were cultured on the EMB, Chocolate, Blood, and Thioglycollate Agar in the laboratory and were incubated for twenty-four hours under thirty-seven degrees centigrade. In instances of growth of microorganism spotted with particular biochemical tests after twenty-four-hour of incubation at thirty-seven degrees centigrade, the type of bacteria was ascertained. In case of growth of microorganisms, the samples were reincubated and the type of the microorganism was established utilizing a table.

The investigator gathered the information of the patient utilizing the checklist of CPIS daily and for instance, their scores were above or equal to 0.6 a chest X-ray was taken (with regards to the opinion of the appropriate physician). Furthermore, a tracheal tube secretions culture was forwarded to the laboratory a definite diagnosis. Oral care examination and protocol of the patients for the incidence of VAP were conducted until forty-eight hours after the exclusion of the tracheal tube, detection of obvious aspiration, the occurrence of pneumonia, discharge from the hospital, allergic reactions to chlorhexidine solution, death or twenty-eight days. In the current research, the result measures comprised of duration of mechanical ventilation (days), length of ICU stay, mortality rate in the ICU, ventilator free-days at day twenty eight, the consequence of oral rinse with 0.2 percent and two percent chlorhexidine on the rates VAP and oropharyngeal colonization, and undesirable effects of chlorhexidine

(Nieszkowska et al. 2015).

The information was inputted into SPSS statistical software, version nineteen and examined utilizing the chi-square test, Mann –Whitney U test and the t-test. A figure of p less than 0.05 was contemplated to be significant statistically. The information was presented as mean plus or minus Standard deviation or interquartile range and median. At the time of the 5-month research period, four hundred and fourteen patients were admitted to the wards under research; however, two hundred and ninety-seven were exempted

Discussion

Minimizing VAP through oral care is key to prevent the increase of microorganisms that are resistant to an antibiotic. In the current research, two percent chlorhexidine was selected since prior research demonstrated that this concentration was more useful compared to other concentrations in a patient that have a high threat patients and demonstrated good activity in opposition to multi-drug defiant bacteria in the environment of the laboratory. The current research demonstrated that the greater concentration of chlorhexidine (two percent) was useful in minimizing the occurrence of VAP. These results are constant with those of Koeman, Azab, and Tantipong. Tantipong conveyed that the occurrence of VAP was 4.9 percent in the chlorhexidine group and 11.4 percent in the saline group. Additionally, Koeman stated that the occurrence of VAP in chlorhexidine, placebo, and chlorhexidine classes was ten percent (n=13), eighteen percent (n = 23), and thirteen percent (n=16), correspondingly. The outcomes demonstrated that two percent chlorhexidine was more efficient than 0.2 chlorhexidine against both gram-negative and gram-positive bacteria

(Scannapieco. 2016).

Nevertheless, two percent of chlorhexidine was less efficient in opposition to Acinetobacter. This was ascribed to the organism’s drug resistance and prevalence. The outcomes are similar to those of Tantipong and Koeman. The mixture of two percent chlorhexidine and two percent chlorhexidine-colistin were similarly efficient in minimizing oropharyngeal gram-positive colonies. Nevertheless, the mixture of chlorhexidine-colistin was more efficient in gram-negative microorganism in contrast with chlorhexidine on its own (p < 0.001). In the research by Tantipong, colonization of oropharyngeal with gram-negative bacilli was either delayed or reduced in patients who had gotten chlorhexidine two percent. In that research, more than sixty percent of patients who had gotten oropharyngeal colonization that is gram-negative that was associated with underneath patients and diseases preceding hospitalizations. Correspondingly, Kusahara and Scannapieco demonstrated that chlorhexidine did not minimize the accumulated number of gram-negative microorganisms. The results of the current research demonstrated that oropharyngeal pathogens were comparable to pulmonary pathogens in VAP patients

(Grap et al. 2013).

Moreover, pathogens of VAP by this time was present in the tract of oropharyngeal. Treloar stated that 37.5 percent of oropharyngeal samples from tracheal tube patients had comparable microorganisms to samples of tracheal. However, disparities in the forms of microorganisms segregated from samples in the research might consequence from disparities in the forms of the prescribed antibiotic, periods, and concentration of antibiotics, research methodologies and prevalence rates of bacteria.

The present research disclosed that reversible and mild oral mucosa irritation took place in the two groups, and discoloration of the teeth took place in the 2 percent group of chlorhexidine

(Munro & Grap. 2014).

Nevertheless, oral mucosa inflammation was minimized following the gentle cleaning of the mucosa of the oropharyngeal. Therefore, appropriate cleaning of the teeth before utilizing chlorhexidine could reduce its adverse effects and increase its effectiveness. In the research by Tantipong reversible and mild inflammation of oral mucosa was detected in ten patients which represent 9.8 percent of the chlorhexidine group and in one patient 0.9 percent of the regular group that is saline. Nonetheless, this inflammation was minimized after the nurses were directed to moderately clean the mucosa of the oropharyngeal. In the research by Koeman, tongue edema was witnessed in the chlorhexidine –colistin group on the 2nd day. In divergence, it was reported by Bellissimo-Rodriguez no stern effects that are adverse, even though three patients in the group of the experiment and five in the group of placebo protested concerning the solution’s unfriendly taste.

Comparable to the research by Tantipong, the present research demonstrated that two percent of chlorhexidine did not result in more hostile consequences in comparison to 0.2 chlorhexidine. Thus, in prospective research, the unfavorable outcomes of two percent chlorhexidine have to be examined under the supervision of the dentist. Even though both the groups in the current research were not substantially diverse in terms of duration of mechanical ventilation, length of the stay in ICU, and the rate of mortality, all this results reduced in the two percent group of

chlorhexidine (Mori et al. 2016).

This result conforms with those of most research undertaken on the matter. The disparity between the outcome of the current research and those of others might be credited to disparities in methods and protocols of VAP prevention, place and time of intervention, treatment methods, populations under scrutiny and protocols for the discharge of patient’s. In the present research, intensivists and laboratory endorsing the analysis of VAP did not know concerning the intrusions. Furthermore, the researchers undertook continuous oral care based on the protocol

(Feider et al. 2010).

This intensified the research’ preciseness. Contrarily, even though uninformed of the assignments of the group the researcher was liable for finalizing the checklist for CPI, examining the mouths of the patients, doing oral care and bias might have taken place.

Based on the research by Wallace, the description of the CDC should be utilized for surveillance, since it may miscalculate the occurrence of the VAP. CPIs can also over-approximate the occurrence of the VAP. In the present research, tracheal and oropharyngeal cultures were semi-quantitative. Due to the low costs and the convenience, semi-quantitative reports of culture are usual in the VAP analysis, nevertheless, its specificity and sensitivity are not as important as those of a culture report that is quantitative are.

Conclusion

In the current research, there was also challenges disturbing appropriate oral care because of the existence of oropharyngeal airways and tracheal tubes and some restlessness. As well, numerous elements, for instance, diverse interventions and sample size that were out of control of the investigator disturbed the VAP development. These could have led to the drawbacks in assessing the benefits of oral care.

In conclusion, the results of the present research demonstrate that oral discontagion is greatly efficient with two percent chlorhexidine than with 0.2 percent chlorhexidine in minimizing the incidence of VAP and the oropharyngeal colonization

(Grap et al. 2014

). These results may form the ground for continued clinical use and trials of the two percent in such instances.

References

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Florence Nightingale was born May 12th, 1820 to parents William and Frances Nightingale during the second year of their honeymoon tour and was named after the city of her birth, Florence, Italy. She was their second child, her older sister Parthenope was born one year prior and was also named after the city of her birth, Naples, or Parthenope in Greek (The Florence Nightingale Museum Trust, n.d.). Her parents were wealthy Unitarians and traveled in the highest English social circles. Her maternal grandfather was a liberal politician who believed in philanthropy and abolitionism (Attewell, 1999). Her father William, who had studied at Cambridge according to the Nightingale Museum website, was progressive for his time and taught his daughters mathematics, statistics, philosophy, history, economics, government, and multiple languages (Johnson & Weber, 2005). Florence was particularly interested in mathematics which she would later use to support her observations (The Florence Nightingale Museum Trust, n.d.). Her mother Frances was religious and although Unitarian she preferred the Church of England and her girls where raised in the church (O’Conner & Robertson, 2003). Florence felt a strong calling by God to help the sick and the poor and was finally able to convince her parents to allow her to attend nursing school at the school for deaconesses at Kaiserswerth, near Dusseldorf Germany in 1851 after she had visited there while on her European tour with family friends (The Florence Nightingale Museum Trust, n.d.). After graduating, she visited hospitals throughout England and Europe, studying their design and the incidence of disease through hospital reports and government publications (Attewell, 1999). In 1853, she accepted her first position as the superintendant of An Establishment for Gentlewomen during illness in London. War broke out in 1854 when Russia invaded Turkey and England and France went to Turkey’s aid. Florence was asked to nurse British soldiers by her friend Sir Sidney Herbert, the Minister of War, after the public outcry over the number of deaths and the conditions of the hospitals for soldiers fighting in Turkey. She worked tirelessly caring for the ill and wounded with the other 37 female nurses she had recruited and became known as the “Lady with the Lamp” because she would check the wards at night using a lamp to light her way. During her time in Turkey, she became extremely ill with what is believed to be brucellosis which continued to plague her for the rest of her life. Florence returned to England after the war in 1856 and began to use mathematics and statistics to help her write and support her notes on the army, hospitals, and the causes of death of soldiers she cared for in Crimea. She is credited with creating the “polar area” or pie chart as it is know today (The Florence Nightingale Museum Trust, n.d.). She was upset by the number of soldiers who died from communicable disease versus war injuries and became semi-reclusive communicating primarily in writing (McDonald, 2009). It has been suggested that she was suffering from Post Traumatic Stress Disorder from her experiences during the war (Mackowiak & Batten, 2008). In 1857 she declined her third offer of marriage to devote her life to the care of the sick and social reform. She wrote Notes on Nursing, the basis for her Environmental Model in 1859. The Nightingale Training School at St. Thomas Infirmary opened in 1860 utilizing money that was given to her as thanks for the care she provided to the soldiers in Crimea with the training for nurses being based on her model. In 1864, Florence helped to develop home nursing, hospitals for birth, the insane, and the poor, barracks for married soldiers, and the practice of separating the sick by gender, age, and disease. She continued to write on health and social reform issues such as rural hygiene, deaths during birth, and lying in institutions throughout her life despite being ill and bedridden for extended periods. In fact, she published over 200 books, pamphlets, and reports during her lifetime. The founder of the Red Cross, Henry Dunant, credits Nightingale with giving him the inspiration to create the Red Cross in 1872. Her father, who continued to support her financially and was the one person she allowed to see her on a regular basis, passed in 1874. Her mother followed in 1880 and her sister in 1890. In 1902 Florence became bed ridden for the last time and remained so until her death in 1910. For her contributions to society, public health, and nursing, Florence was awarded multiple commendations and medals including being elected the first female Fellow of the Royal Statistical Society in 1860, the Royal Red Cross in 1883, the first woman recipient of the Order of Merit in 1907, and the Freedom of the City of London in 1908 (McDonald, 2009).

Florence Nightingale was many things during her lifetime: nurse, researcher, statistician, social reformer, educator, and theorist. Her contributions to nursing and society are numerous. Florence Nightingale has been referred to as the “mother of modern nursing” (Johnson & Webber, 2005). Before she became a nurse, it was common belief in England that nursing was only for holy sisters and women of low birth or moral character who were considered prostitutes, drunks, and thieves. Through her work and example, nursing became a respectable profession for women (The Florence Nightingale Museum Trust, n.d.). She tirelessly collected data through observation and research and applied that knowledge to social reform on the issues of public and military health and sanitation at home and abroad, rural hygiene, hospital planning, organization, and administration, rights of women and the poor, the definition of nursing, and the need for trained nurses and midwives to care for people in workhouses, hospitals, schools, penitentiaries, the military, and at home (Wellman, 1999). Due to the nature of her work and her commitment to improved patient outcomes by developing best practices based on observation and research, she should be considered the first public health nurse and champion of Evidence Based Practice.

Florence was a statistician and an educator. She used her knowledge of math and her research to support her ideas and the necessity of reform (O’Connor & Robertson, 2003).

She is responsible for initiating the professional education of woman in nursing outside of the sisterhood and promoting their employment in hospitals and workhouses throughout England and abroad (The Florence Nightingale Museum Trust, n.d.). Beyond nursing education, she was instrumental in changing military medical education through her observations during the Crimean War. In her Notes on matters affecting the health, efficiency and hospital administration of the British Army Florence writes:

[…] whatever amount of scientific information appears to be presented by the civil student on his entrance into the Army, they convey little or no evidence of his practical knowledge. But as his entrance into the Army instantly introduces him into practice, and in a very short space of time submits patients to his charge, it seems necessary that a school of that kind which exercises the pupil in practical knowledge should intervene between his entrance into the army and his regimental service (Attewell, 1999, p. 5).

It is evident that her influence was genuine as the first Army Medical School in England was opened in 1860 by physicians and surgeons who were veterans of the Crimean War.

Finally, Florence Nightingale was a theorist. She developed her Environmental Model in 1859 and titled it Notes on Nursing: What It Is and What It Is Not based on her observations and experiences while treating the soldiers during the war (Johnson & Webber, 2005). Nightingale wrote:

In watching disease, both in private houses and in public hospitals, the thing which strikes the experienced observer most forcibly is this, that the symptoms or the sufferings generally considered to be inevitable and incident to the disease are very often not symptoms of the disease at all, but of something quite different- of the want of fresh air, or of light, or of warmth, or of quiet, or of cleanliness, or of punctuality and care in the administration of diet, of each or of all of these (Nightingale, 1860, p. 2).

Florence wrote these notes on practice, not intending them to be a manual on nursing, but ideas for women who take care of others because she felt that at some point, nearly every woman nursed somebody in her charge and it was up to them to manipulate the environment to help nature take its course (Nightingale, 1860). Her model includes 13 constructs with recommendations on implementing them. They are: ventilation and warming, health of houses, petty management, noise, variety, taking food, what food, bed and bedding, light, cleanliness of rooms and walls, personal cleanliness, chattering hopes and advises, and observation of the sick (Nightingale, 1860).

Although Nightingale did not intend for her writings to become a teaching manual for nurses, her ideas were clearly applicable to teaching nurses how to care for the patient environment and was eventually used in her school to do just that (Johnson & Weber, 2005). Some of her hints on nursing are still applicable to practice today. They represent a holistic view of nursing by addressing the physical, mental, and social aspects of the patient environment. For instance, cleanliness of air, water, home, linen, and person are still important and helpful in preventing disease and promoting health. Also, adequate nutrition and sunlight are necessary for proper bodily function. Excessive noise and lack of variety can be harmful to mental health and must be remedied. Lastly, as nurses we still observe the sick, keep track of their vital signs, likes and dislikes, and monitor changes in their condition. All of this we record in the patient’s chart much like Nightingale did when she recorded her observations 150 years ago.

Although Nightingale’s Environmental Model does not meet the guidelines of modern theory and has not spawned the same quantity of research as contemporary models, it can be said that her ideas have influenced nursing theorists and their respective models. Like all nurse theorists, Nightingale used her personal, spiritual, and educational experiences to guide her ideas (Johnson & Weber, 2005). The Living Tree of Nursing Theories was developed by nurses to illustrate the influence of Florence Nightingale on later nurse theorists. It proposes that person, environment, health, and nursing are the roots of the tree and Nightingale is the trunk supporting the branches, which are the modern theorists (Tourville & Ingalls, 2003). In essence, without Florence Nightingale’s work and ideas, nursing theory would not be the same as it is today. She created the fundamentals on which nursing theory is built. In fact, when comparing modern theories to the Nightingale Model many similarities can be appreciated. Henderson was concerned that the early nurse practice acts did not clearly cover what nursing is and therefore promoted an unsafe environment for the public. She helped define what nursing is and what it was not. Her definition reads:

The unique function of the nurse is to assist the individual, sick or well, in the performance of those activities contributing to health, or its recovery (or to a peaceful death) that he would perform unaided if he had the necessary strength, will, or knowledge. And to do this in such a way as to help him gain independence as rapidly as possible (Johnson & Webber, 2005, p. 133).

A direct connection can be made to Nightingale’s model if one considers the changes in societal expectations and the growth of the nursing role from doer to helper in the 100 years between when the two theories were written. Henderson promotes helping the patient achieve independence through nursing assistance that Nightingale did not. Her 14 components of nursing are similar to Nightingale’s 13. They include: breathe normally, eat and drink adequately, eliminate body wastes, move and maintain desirable postures, sleep and rest, select suitable clothing, maintain normal body temperature, keep the body clean and well groomed to protect the integument, avoid dangers in the environment and avoid injuring others, communicate with others, worship according to one’s faith, work in such a way that there is a sense of accomplishment, play or participate in various forms of recreation, and learn, discover, or satisfy the curiosity that leads to normal development and health using available health facilities (Johnson & Webber, 2005).

Faye Abdellah’s theory titled, Patient-Centered Approaches, is just that, patient centered. Her 21 nursing problems are also similar to Nightingales 13 ideas and when advances in science and understanding of how the human body functions are taken into consideration a direct correlation can be established. Lastly, Sister Callista Roy’s Adaptation Model relies on the construct that the role of the nurse is to manipulate the environment to free patients so that they can adapt to other stimuli. Although this is a deviation from Nightingale’s theory, both nurses believed in the reparative process of providing the optimal environment for healing (Johnson & Webber, 2005).

In conclusion, Florence Nightingale was instrumental in influencing nursing and society by opening the door for women to practice as nurses, promoting nurse education, guiding evidence based practice through her research and observations, by being a human rights advocate, and by working tirelessly to improve the health and quality of life for people throughout many nations. Florence Nightingale devoted her life in the pursuit of helping others.

Diabetes is an increasingly common metabolic disorder distinguished by lack of production or dysfunction of the insulin hormone, resulting in raised blood glucose levels, known as hyperglycaemia (Bailey 2015). In 2015, it was recorded that approximately 415 million individuals had diabetes worldwide, which is expected to increase to 642 million individuals by 2040 (International Diabetes Federation (IDF) 2015). Financially, it was estimated that the total cost for both the direct and indirect care associated with diabetes within the UK is currently £23.7 billion. This is expected to rise to £39.8 billion by the year 2035-2036 (Diabetes UK 2016).

There are two main forms of diabetes mellitus, Type 1 (Insulin-Dependent) and Type 2 (Non-Insulin Dependent). Type 1 is a chronic autoimmune disease which develops following the destruction of the β-cells within the islets of Langerhans throughout the pancreas. The β-cells function by synthesising and secreting insulin in the response to the maintenance of glucose levels. (Bluestone et al 2010) (Kulkarni 2003). When these cells are destroyed, this results in the loss of blood glucose control. Therefore, insulin replacement is the main treatment therapy in order to maintain optimum blood glucose levels (Bacha and Klinepeter 2015) (Bailey 2015). Type 2 (Non-Insulin Dependent) diabetes is the most common type, affecting approximately 85-90% of individuals with diabetes (Hex et al 2012). This type occurs when the β-cells produce defective insulin or when insulin secretion is reduced resulting in insulin resistance and hyperglycaemia (Nyenwe et al 2011). Certain therapeutic treatments can be given to maintain blood glucose levels (Bailey 2015).

At present there is no single drug available that can treat all aspects of diabetes mellitus, due to the complexity of the β-cells within the pancreas. However, there are various medications currently available that can be used in combination with lifestyle changes to reduce hyperglycaemia and maintain blood glucose homeostasis (Bailey 2015) (Breuer et al 2010). Treatment therapy is selected according to the pathophysiology of the individual. More recent approved treatments include SGLT-2 inhibitors, bile acid sequestrants and incretin mimetics (Bailey 2015). More focus being brought to peptide treatment therapy relating to neurotensin (Chowdhury et al 2013).

2.0 Type 2 Diabetes (Non-Insulin Dependent)

The maintenance of blood glucose homeostasis is performed by two hormones secreted from the islet of Langerhans cells in the pancreas. Insulin, secreted from the β-cells and glucagon, secreted from the α-cells (Meece 2007).

Type 2 Diabetes Mellitus develops when the β-cells within the pancreas become dysfunctional and the volume of insulin released is inadequate to maintain glycaemic control (Kasuga 2006) (Nyenwe et al 2011). Hyperglycaemia ensues, increasing the demand for insulin, and to compensate the β-cells excessively release insulin to lower the blood glucose level and over time these cells lose their function (Kasuga 2006).

3.0 Current treatments

The occurrence of Type 2 diabetes continues to increase globally; and whilst the pathophysiology and further complex issues are understood, treatment therapy can be difficult (Nyenwe 2011). Currently approved diabetic drug therapies are listed in

Table 1

.

Table 1. Current approved drug therapy used in the treatment of Type 2 diabetes to aid in the maintenance of blood glucose homeostasis.

DRUG	ROUTEÂ	MECHANISM OF ACTION	IMPLICATIONS
BIGUANIDE Metformin	Oral	Suppresses hepatic glucose production and increase insulin sensitivity within the muscle tissue	Linked to lactic acidosis. Gastrointestinal side effects. Should be avoided in deteriorating renal function or liver impairment.
SULFONYLUREAS Gliclazide Glimepiride Tolbutamide	Oral	Increases insulin secretion by binding to sulfonylurea receptor-1 on β-cells resulting in depolarisation and calcium influx	Weight gain is possible. High risk of hypoglycaemia – need for close blood glucose monitoring.
DPP-4 INHIBITORS Saxagliptin Sitagliptin Vildagliptin	Oral	Inhibits enzyme DPP-4, prolonging incretin hormones (GLP-1 and GIP) half-lives	Association with pancreatitis
SGLT2 INHIBITORS Dapaglifozin	Oral	Inhibit Sodium-Glucose-Co-transporter-2 proteins to increase glucose elimination in urine	High risk of developing genital and urinary tract infections. High risk to hypoglycaemia.
GLP-1 MIMETICS	Subcutaneous injection	Binds to GLP-1 receptors causing an increase of insulin secretion, reduce glucagon secretion, delay gastric emptying and appetite suppression	Association with pancreatitis and can cause gastrointestinal side effects. Should be avoided in deteriorating renal function.
Bile Acid Sequestrants	Oral	The mechanism is still uncertain. It is thought that this drug interferes with the enterohepatic circulation of bile acids to lessen their effect; increasing glucose metabolism and advance GLP-1 secretion	Association with gastro intestinal disorders and elevated triglyceride levels.

3.1 Metformin

This is the preferred first-line drug choice to treat Type 2 Diabetes Mellitus. This drug is part of the biguanide class and its main role is to reduce and maintain blood glucose levels without the risk of hypoglycaemia (extremely low blood glucose levels) and weight gain (Chatterjee 2015). It reduces glucose levels by suppressing hepatic glucose output and increasing insulin sensitivity in muscle cells (Bailey 2015). This drug can be used with used alone, but may be more effective when used in combination with other diabetes therapies, such as DPP-IV inhibitors, sulfonylureas and insulin. (Chatterjee 2015) (Ahren 2008).

3.2 Sulfonylureas

This drug stimulates the secretion of insulin from pancreatic β-cells, by binding to the sulfonyurea receptor subunit of ATP sensitive potassium channel, closing it (Prors 2002). This closure causes depolarisation of the membrane, producing an influx of calcium, activating insulin secretion (Bailey 2015). This drug can only work correctly depending on sufficient β-cell function within the pancreas to assist in the release of more insulin (Bailey 2015).

3.3 DPP-IV Inhibitors

This drug functions by inhibiting the action of enzyme DPP-IV from breaking down incretin hormones, in particular GLP-1. Prolonging the life of the incretin hormone allows it to perform its role and stimulate insulin secretion of the pancreatic β-cells (Seino 2010).

3.4 Sodium Glucose Transporter-2 (SGLT-2) Inhibitors

SGLT-2 proteins present in the proximal convoluted tubule of the kidney are responsible for renal glucose filtration and reabsorption (Rizos and Elisaf 2013). Inhibitors of SGLT-2 competitively bind to and block the proteins reducing the amount of glucose reabsorption in the blood but increasing the amount of glucose excreted in urine (Bailey 2015). Associated with the elimination of glucose in urine, the use SGLT-2 inhibitors increase the risk of genital and urinary tract infections (Bailey 2015).

3.5 GLP-1 MIMETICS

3.6 Bile Acid Sequestrants

Bile acids are produced in the liver and upon release promote the absorption of fatty acids (Hansen 2014). However, it has been found that bile acids are associated with the regulation of glucose homeostasis (Nguyen 2008). The exact mechanism of the bile acids sequestrants is unknown, but it has been investigated that this drug inhibits the binding of bile acids to the corresponding receptors, TGR5 and Farnesoid-X-receptor (FXR) interrupting the enterohepatic bile acid circulation and increasing the utilisation of glucose. (Hansen 2014) (Bailey 2015).

?5.0 Combination Treatment Therapy

More recently combination drug therapy has been analysed and proved to have beneficial effects in rodents, such as GLP-1-GIP-GCG triple incretin agonists (Gault 2013).

4.0 Gut Peptides

The intake of food generates the release of two primary incretin hormones; Gastric inhibitory polypeptide (GIP) and Glucagon-like peptide (GLP-1) (Seino et al 2010). Secreted from the intestinal K-cells and L-cells respectively (Bailey 2015), these hormones are released to stimulate insulin secretion to aid in glycaemic control and have a positive effect on the survival of β-cells (Brubaker 2006).

4.2 GLP-1

This 31 amino acid hormone chain, not only inhibits glucagon release and stimulates insulin secretion, also has been discovered in the Central Nervous System promoting satiety (Seino et al 2010) (Gallwitz 2005).

GLP-1 agonists are more recently used as peptide drug to treat type 2 diabetes mellitus (Fosgerau 2015).

5.0 Neurotensin

A neuropeptide secreted from endocrine cells in the gastrointestinal tract, was found to have two important roles in glycaemic control by increasing the release of insulin in low glucose concentrations and decreasing the release of glucose-mediated insulin (Gruundal et al 2016) (Béraud-Dufour 2010). Neurotensin also functions to protect the pancreatic β-cells from apoptosis in patients with Type 2 diabetes (Mazella 2012).

6.0 Xenin

Xenin, a 25 amino acid gut peptide derived from the K-cells in the small intestine (Wice et al 2012). This peptide was initially identified in the human gastric mucosa, and it was further discovered in the liver, pancreas, hypothalamus and stomach (Parthsarthy 2016). It is co-secreted from the K-cells along with GIP following the consumption of high-fat meal increasing the concentration of this peptide in the plasma (Martin et al 2012) (Wice 2012). Natural occurring xenin has been known to have a restricted therapeutic effect due to break down by plasma enzymes (Martin et al 2016). A hybrid peptide Xenin-25(gln) was generated by substituting Arginine and Lysine amino acids present on natural Xenin-25 with Glutamine (Parthsarthy et al 2016).

8.0 Modified gut peptide

Hybrid peptides have been generated via fusion of vital sequences in amino acid chains (Hasib et al 2016). These modified peptides increase the therapeutic ability of antidiabetic drugs, which can be given in one drug combined, rather than separate forms (Hasib 2016).  Recent studies assessing the therapeutic activity of the hybrid peptide xenin-8-gln, in the treatment of Type 2 diabetes (Hasib et al 2016) compared to constituent parent peptides, indicate a potential for the use of hybrid peptides in the treatment of diabetes.

9.BRIN BD11 Cells

Electrofusion of rat pancreatic islet cells and RINm5F cells produced a hybrid cell line known as BRIN-BD11 cells (McClenaghan et al 1996) (Davies et al 2000). It was found that this cell line had similar properties and responses when compared to normal β-cells (Davies et al 2000).

10.0 Conclusion

Recent research has demonstrated that new therapeutic treatments are needed as the incidence type 2 diabetes mellitus is increasing globally. Hybrid peptides are becoming more popular in the field of diabetes treatment. By generating a long acting modified peptide (Q8Q9W11) neurotensin-K6-L-glutamyl-PAL it will be investigated how effective it will be at stimulating insulin secretion compared to non-acetylated constituent peptides. This modified peptide, along with control peptide counterparts will be commercially synthesised and purified using HPLC. The insulin secreting properties of the modified peptide will be measured, recorded and analysed at various glucose concentrations within BRINBD-11 cells. This could further develop treatment for type 2 diabetes.

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