NURS1111 Nursing Research and Evidence-based Practice

Question-1

Critical Appraisal of the selected study

In this context the selected evidence is published by van den Bosch with the title of “The diagnostic accuracy of the squeeze test to identify arthritis: a cross-sectional cohort study”. The researchers conducted the cross-sectional cohort study with the objective of measuring the effectiveness of the squeeze test in screening rheumatoid arthritis in metatarsophalangeal (MTP) and metacarpophalangeal (MCP) joints [1]. Critical appraisal of research journals is a crucial skill that academic healthcare experts, as well as those involved in clinical practice, must learn. A comprehensive review of the published literature is a crucial stage in medical practice before implementing modifications into their patients' care. A critical review of the literature can assist in distinguishing between beneficial and faulty research [2]. In this context, the tool that have been used to critically appraise the research paper is the CASP tool. The CASP tool is one type of general tool for analyzing the strengths as well as limitations of a qualitative research technique. The tool incorporates few questions, each question addressing a distinct methodological element of a qualitative investigation [3].

In case of Cohort study, the first criterion of the CASP is that if the research addressed the focused issue clearly. In this research study, the researchers addressed the patient population clearly and included the patients who were referred with arthralgia (symptom duration of less than 2 year) or have confirmed rheumatoid arthritis. Also, the study mainly focused to find out the diagnostic accuracy of the squeeze in screening for arthritis. The researchers also mentioned the specific joint areas such as metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints which fulfilled the first criterion of the CASP tool for cohort study [2].

The following question in the CASP tool is that if the cohort is done in an acceptable way. In this context, the patients in recent onset refereed with arthralgia (less than 2 year) or the patient had a clinical suspicion for progression of arthritis or clinically apparent arthritis were included. Patients with arthralgia who had symptoms other than suspected or obvious arthritis during their first visit were not examined because there was no scientific reason to execute the squeeze test. As this article did not compare the effect of squeeze test on the patients with obvious arthritis during their first visit hence there might be a scope for selection bias [4]. In addition, inclusion of volunteers in the study also increased a scope for selection bias which was evident in this research. The next portion of the CASP tool is that if the exposure accurately measured in the research to minimize the bias. In terms of subjective data assessment, the researchers included a total 152 patients and focused to measure the reference value for abnormal MRI inflammation made on healthy volunteers. In contrast, the researchers also studied rheumatoid arthritis MRI score (RAMRIS) to capture the inflammation of subclinical joint.

The following question of the CASP tool urged for if the follow up of subjects was complete enough. The participants were investigated between 2013 (August and October), and March 2014; gathered information from the end of the October to mid-November were lost owing to a technical fault with the MRI scanner. Furthermore, from October 2013 to March 2014, 47 symptom-free participants were recruited. From this aspect, the follow up of subjects was not complete enough.

The following portion of the CASP tool is to measure the result and finding out if the result is precise. In the research article, the results indicated that a positive squeeze test is related to both MCP and MTP swollen joints (p<0.005). At the MCP joints, the test’s sensitivity was 53%, positive likelihood ratio (LR+) 3.0, specificity 82%, negative likelihood ratio (LR-) 0.6 as well as area under the receiver operator characteristic curve (AUC) 0.68. The result also stated that, the specificity 74%, sensitivity was 54%, likelihood ratio + 2.1, likelihood ratio - 0.6 as well as AUC 0.64 at MTP joints. The sensitivity as well as specificity for the analysis at the MCP and MTP joints were 39 percent and 86 percent, respectively, with inflammation detected in MRI as the result. The result precisely stated about all the possible outcome and measured all the elements that found the effect of the squeeze test on MCP and MTP joints. As the researchers analyses the MRI inflammation score by using the IBM SPSS statistics V.20 which enhanced the accuracy chances of test results hence there is a strong rationale for believing the test results.

As per the next portion of the CASP tool the result of this research is very similar to other researches based on the same topic. Wouters, Niemantsverdriet and van der Helm-van also researched on finding effect of the squeeze test in detecting the subclinical synovitis in arthralgia patients [5]. The researchers stated that approximately 51 % of patients with clinically suspect arthralgia had a positive squeeze test in MTP or MCP joints. The research observed a positive squeeze test in measuring subclinical synovitis, with a specificity of 72% (95% CI 68–76%) as well as sensitivity of 44% (95% CI 33–55%). This result is quite similar to the result of research of van den Bosch and that enhances the authenticity and result accuracy of the research. At last, the researchers concluded that a positive squeeze test is related to local joint inflammation, but its accuracy is limited, showing a significant proportion of swollen joints in the absence of a positive squeeze test.

Question-1-b: Role of the “squeeze test” for diagnosing rheumatoid arthritis

Rheumatoid arthritis (RA) is the foremost usual chronic inflammatory disease of the joints in the body. This inflammatory disease can be characterized by swelling as well as stiffness of joints. The feet and hands are perhaps the most often affected joints, namely the metatarsophalangeal (MTP) joints, metacarpophalangeal (MCP) joints, as well as proximal interphalangeal (PIP) joints [6]. In diagnosing the inflammatory join disease, squeeze test is used which is an easy, cheap and rapid method to diagnose the arthritis in the metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints, promoted by some experts [7]. The squeeze test may aid in the quick identification of ‘clinical suspicion' of Rheumatoid Arthritis in primary care patients. It has been observed that, tenderness with lateral squeezing of the MCP or metacarpophalangeal joints on a patient with active synovitis is characterized by the Gaenslen's compression manoeuvre (GCM) or squeeze test (ST) positive.

The squeeze test can be used to determine the existence of synovitis. Firm pressure is applied over the metacarpophalangeal joints located in the fingers and the metatarsophalangeal joints located in the foot. This should not be uncomfortable in unaffected joints, but it will be severe in RA-affected joints. The individual may also find it difficult to create a full fist, with the fingernails entirely buried within the fist. Joint deformity is common in established RA and might not be shown in new instances. It has also seen that, a positive squeeze test in individuals with arthralgia who are suspected of having rheumatoid arthritis (RA) increases the likelihood of having subclinical synovitis.

Question-2

Critical Appraisal of the selected study

In this portion, the critical appraisal will be done of the research published by Whiting and colleagues (2010) which was published with the title of “Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis”. From the title it can be clearly evident that this is a systematic review, where the researchers reviewed the diagnosis accuracy of Anti-citrullinated peptide antibodies (ACPA) in determining rheumatoid arthritis. The systematic review stated that early recognition of rheumatoid arthritis as well as its treatment is very crucial in preventing irreversible damage of the joint. The authors added that Anti-citrullinated peptide antibodies (ACPA) test is considered as one of the leading diagnosis factors in early diagnosis of Rheumatoid arthritis. The researcher’s objective was to compare the accuracy of rheumatoid factor and Anti-citrullinated peptide antibodies (ACPA) in diagnosing the early symptoms of the rheumatoid arthritis among the patients with the disease [8]. In this portion, the tool that have been utilized in critically appraising the research paper is the CASP tool. The CASP tool is a general tool for analyzing the strengths as well as limotations of any qualitative research technique. The tool consists of total 10 questions, each addressing a distinct methodological element of a qualitative investigation [3].

The first portion of the critical appraisal for systematic review is that if the review addressed the research question clearly and if the question is focused. In this context, the researchers clearly stated the research question and the focus was to determine the accuracy of the Anti-citrullinated peptide antibodies (ACPA) in measuring Rheumatoid arthritis and comparing the data with another diagnosing method with Rheumatoid factor (RF). The second portion or question of the critical appraisal on CASP tool is that if the researchers search out for the right type of papers which is relevant to the topic. The researchers searched total 10 medical databases such as MEDLINE, Science Citation Index, EMBASE, and BIOSIS from inception to September 2009, and no restriction of publication or language were followed, as well as references of incorporated studies. The researchers confined their search to keywords associated with ACPA and rheumatoid arthritis. The researchers did not apply any methodological criteria to select diagnostic studies since doing so would lead the omission of important studies. The researchers further classified eligible studies as diagnostic cohort, cross-sectional, nested case–control studies, case–control of any form of ACPA used to detect rheumatoid arthritis by utilizing documented technique. The third portion of the CASP tool for systematic review is that if the researchers included all the important and relevant studies in their study. In this context, the researchers searched 10 databases mentioned above and then included all the relevant and important studies such as diagnostic cohort, cross-sectional, nested case–control studies, case–control of any form of ACPA used to detect rheumatoid arthritis. The next question of the CASP systematic review tool is that if the researchers of the review did enough to evaluate quality of the included studies. In such context, it was seen that the researchers did not use any methodological filter to recognize the diagnostic studies. However, titles and abstracts were reviewed separately by two reviewers. The researchers then collected full-text publications that they thought could be relevant. One reviewer assessed the inclusion and then was double-checked by another which made the research more authentic. The following portion of the CASP systematic review tool is that if the results or outcomes of the review have been combined, and if it was reasonable. The provided data in studies individually for various control groups or phases of rheumatoid arthritis, the researchers merged them into “rheumatoid arthritis” as well as “non–rheumatoid arthritis” groups. Data from individuals with nonspecific arthritis, as well as records from healthy control participants, were omitted by the researchers. In sensitivity analyses, the researchers looked at the effect of categorizing patients with nonspecific arthritis as rheumatoid arthritis or non–rheumatoid arthritis, as well as the effect of choosing various types of control sets in diagnostic case–control studies. Furthermore, the authors combined findings from cohort, cross-sectional, and case–control studies independently to evaluate heterogeneity. The studies were further subdivided by illness stage (early vs. mixed or developed rheumatoid arthritis) and the ACPA test. The efficacy of IgM rheumatoid factor was compared with that of ACPA in trials that provided data from both tests, according to the researchers. As per the CASP tool the following section focused on the results of the study, which stated that summary sensitivity as well as specificity of were 57 percent (95 percent CI, 51 percent to 63 percent) as well as 96 percent (CI, 93 percent to 97 percent) in cohort studies that examined anti-cyclic citrullinated peptide antibodies (anti-CCP2) in second-generation patients who had detected with early rheumatoid arthritis. Sensitivity was exaggerated in case-control and cross-sectional investigations, as well as in studies of individuals with diagnosed rheumatoid arthritis. Anti-CCP2 antibodies exhibited higher specificity than rheumatoid factor antibodies (96 percent vs. 86 percent), but equal sensitivity. There was inadequate evidence to determine if the combination of rheumatoid factor and anti-CCP2 offers an extra advantage over anti-CCP2 alone. On appraising the findings of the study, it can also be stated that almost all investigations were free of partial and differential verification bias, as well as incorporation bias. Most of the studies did not specify whether ACPA interpreters were blinded to the final diagnosis as well as vice versa, or if sufficient clinical information was provided to the ACPA interpreter. In several trials, it was unclear if any patients left or whether any findings were ambiguous or inconclusive. As per next criterion of CASP tool, rheumatoid arthritis therapy should begin as soon as feasible in the illness process. Initial symptoms may represent an immunopathological unique phase of the illness; therapy with disease-modifying antirheumatic medications during this time period may have the greatest ability to prevent erosions or perhaps turn off the disease. The use of ACPA may enable for a diagnosis to be established extremely early in the illness process, even before symptoms appear, which may have major consequences for proper therapy. The researchers included all the important and relevant studies, data and facts however there is limitation of the study. The majority of investigations employed a diagnostic case-control approach, which overstated sensitivity. Items pertaining to the quality of the study were rarely mentioned. It was not possible to measure publication bias. In the last portion of the research the authors stated that although anti CCP2 is a more expensive test than IgM rheumatoid factor, its greater specificity, for diagnosing a disease with expensive long-term sequelae if it is not treated promptly, suggests that its introduction could be cost-effective. Based on this, the researchers concluded that Anti-CCP2 need to be included in the diagnosis of the patients with early rheumatoid arthritis symptoms.

Question-2-b: Role of Anti-citrullinated peptide antibodies:

CCP antibodies, which is also known as anti-CCP antibodies, are a kind of antibody known as an autoantibody. These antibodies as well as autoantibodies are proteins that the immune system produces. CCP antibodies attack the healthy joint tissues. In case CCP antibodies are detected in blood, it may indicate rheumatoid arthritis. This join disease is an autoimmune illness that results in joint pain, stiffness, and inflammation. CCP antibodies are detected in 75% or above in rheumatoid arthritis patients [9].

Clinical studies now employ anti-citrullinated peptide antibody (ACPA) assays, which were developed and sold in the previous decade. ACPA are a useful screening test early onset of the disorder since they may be diagnosed before the RA symptoms onset and so are indicative of RA progression. Anti-CCP testing is extremely significant in the diagnosis of RA due to the high specificity with which symptoms emerge and the ability to identify patients at risk of severe disease and irreversible damage [10]. The higher specificity of Anti-CCP can help distinguish Rs from other diseases that appear and function clinically like RA in its early stages.

From the aspects of the clinical utility of Anti-citrullinated peptide antibodies it can be said that Anti-cyclic citrullinated peptides are triggered to the antigens which consists of citrullyl residues converted from arginyl by peptidylarginyl deiminase enzymes. It has been shown that the acidic or neutral isoform of filaggrin, which is an intermediate filament-associated protein (IFAP), is identified by RA-specific autoantibodies. During the final development of the mammalian epidermis, filaggrin is produced as profilaggrin, which have high-molecular-weight insoluble precursor stored in keratohyalin granules. Profilaggrin is dephosphorylated and proteolytically cleaved once the granules are dispersed, releasing the soluble filaggrin. Peptidylarginine deiminase (PAD), a calcium-dependent enzyme, eventually catalyzes the transformation of arginine residues to citrulline residues in filaggrin [11]. This post-transcriptional alteration, known as deamination or citrullination, results in the production of citrulline, which is an amino acid that's been characterized as the key material of antigenic determinants identified by RA-specific autoantibodies [10]. Exracellular Ca2+ increases in Rheumatoid arthritis can activate PADs and that eventually cause citrullination of different proteins. Extracellular Ca2+ may also stimulate peptididylarginine deiminases produced by dying cells. While large-scale cell death takes place, such as during inflammation, clearance systems may be unable to eliminate apoptotic remains adequately. As a result, the citrullinated proteins come into interface with the cells of the immune system, that potentially triggering the ACPA response [11]. The discovery of ACPA was a significant step forward in our knowledge of the pathophysiology of RA. ACPA-positive and ACPA-negative illness have been linked to various genetic and environmental factors, indicating that different pathophysiological processes underpin these two distinct disease subgroups. Patients with RA have an aberrant humoral response to citrullinated proteins, which are expressed in any kind of inflammation, including the synovium. Citrullinated proteins are normally destroyed on a regular basis and do not trigger any significant humoral immune system response; hence, the presence of citrullinated proteins does not always result in chronic inflammation. Citrullination has been found to be a process prevalent in a wide spectrum of inflammatory tissues, implying that it is an inflammation-related event that the immune system should typically accept. Lastly, it can be added that PAD-containing immune cells infiltrate inflammatory tissue (joint). Citrullination of target antigens is promoted by PAD activation caused by elevated intracellular calcium concentrations after cell death. Ineffective clearance of apoptotic cell remains allows intracellular antigens to remain accessible to the immune system for an extended period of time. Citrullinated peptides will be processed and presented to T lymphocytes by antigen presentation cells (APC). Activated T cells in vulnerable people will stimulate B cells, causing them to produce autoantibodies. This will eventually lead to the development of immunological complexes, which will be followed by an increase in pro-inflammatory cytokines.

Question- 3

In this section, the focus is to carry out an evidence-based practice on the topic of rheumatoid factor test and its comparison with anti-cyclic Citrullinated Peptide Antibodies and measuring the effectiveness of Rheumatoid arthritis diagnosis. To carry out evidence-based research, it is necessary to develop a research question as well as aim that will aid in focusing the search for evidence as well as assist in conducting the review. PICO was used to create the present research question. When using PICO, the patient population or issue is indicated as P, the intervention technique is represented as I, the comparison with just another treatment or the control group is represented as C, and the result or effects of the therapy on the patient is denoted as O [12]. In this context the P is the patients with Rheumatoid Arthritis, ‘I’ is the using Rheumatoid factor (RF) test, C is the anti-cyclic Citrullinated Peptide Antibody test and O stands for outcome of the Rheumatoid factor on RA diagnosis. So, the research question in this context is “Is the diagnostic accuracy of rheumatoid factor more in comparison with anti-citrullinated peptide antibodies?”.

To conduct out the research, search terms of the research were first created and searched in multiple databases. Search terms are important since they aid in the discovery of credible documentation to the research topic. The following search terms of the research were used in this context: rheumatoid factor, anti-citrullinated peptide antibodies. Arthritis rheumatoid”. All of the search terms were obtained by using ‘AND,' ‘OR,' and ‘IN' inside the search boxes. Extending the search with more keywords does not automatically improve the output. PubMed, Google Scholar, NCBI, CINAHL, Cochrane Database, and Psych Info were used to find the review papers.

Anti-cyclic citrullinated peptides (anti-CCP), on the other hand, are a form of autoantibody that acts against the body's natural antibodies. Anti-CCP is frequently generated when a person has rheumatoid arthritis. These autoantibodies begin to target and destroy normally healthy tissue [14]. Anti-CCP testing is only 50 to 75 percent sensitive for rheumatoid arthritis. Anti-cyclic citrullinated peptides (anti-CCP) are a kind of autoantibody which attacks the body's natural antibodies. Anti-CCP is frequently generated when a person has rheumatoid arthritis. The auto antibodies tend to attack and destroy normally healthy tissue [14]. Anti-CCP testing is only 50 to 75 percent sensitive for rheumatoid arthritis.

In this context, the first evidence that can be taken is published by Nishimura and colleagues (2007), where the researchers enrolled a total of 10 participants as well as examined the role and accuracy of Rheumatoid factor and anti-CCP antibody in the prognosis or diagnosis of suspected in rheumatoid arthritis. The researchers included DerSimonian-Laird random-effects process in summarizing the specificities, sensitivities, as well as positive as well as negative likelihood ratios of anti-CCP antibody and Rheumatoid factor [15]. The pooled specificity, sensitivity, as well as positive probability ratios and negative probability ratios for anti-CCP antibody were 67 percent (95 percent CI, 62 percent to 72 percent), 95 percent (CI, 94 percent to 97 percent), 12.46 percent (CI, 9.72 to 15.98), and 0.36 percent (CI, 0.31 to 0.42). The results for IgM RF were 69 percent (CI, 65 percent to 73 percent), 85 percent (CI, 82 percent to 88 percent), 4.86 percent (CI, 3.95 to 5.97), and 0.38 percent (CI, 0.33 to 0.44). The likelihood ratios of IgG RF, IgM RF, and IgA RF appeared to be comparable. The findings from the included patients studies with early rheumatoid arthritis were consistent with the findings from all investigations. The major portion of the included studies discovered that anti-CCP antibody positive increased the risk of radiographic progression more than IgM RF positivity that in turn prove the higher accuracy of RF test compared to anti-CCP antibodies test [15]. Another evidence published by Bas and colleagues (2002) examined the value of immunoglobulin M rheumatoid factors (IgM RF) which was compare to anti‐cyclic citrullinated peptide (anti‐CCP) antibodies, as well as anti‐keratin antibodies (AKA) in determining or diagnosing rheumatoid arthritis (RA). The researchers conducted a cross-sectional study where they determined the examining factor by using 179 patients of Rheumatoid arthritis and compared the data with 50 participants as a control group. The result of study indicated that the sensitivity was 75% in IgM RF which was the highest, followed by 68 % for anti‐CCP antibodies as the well as 46% for anti‐keratin antibodies. However, the specificity was greater in anti‐CCP antibodies test which is 96%, then 94% specificity for AKA and then 74% specificity for IgM RF. Also, the presence of IgM RF was shown to be associated with clinical symptoms and the severity of erosions. The researchers concluded that, Anti CCP antibodies, due to their high specificity, can aid in the diagnosis of RA, although immunoglobulin M rheumatoid factors is a stronger predictor of progression of disease in rheumatoid arthritis.

Question-4

The process of developing a good research question may be difficult and unpleasant. While a complete literature analysis is required, the researcher frequently meets methodological challenges throughout the study's execution, especially if the key study question was not appropriately selected in line with the clinical issue that has to be addressed. As a result, optimizing time and resources before beginning on the creation of a clinical protocol might have an influence on the research project's end findings [17].  A well-developed research topic is a good place to start when undertaking a quality research project or implementing evidence-based clinical practice. Research objectives are critical because these are more than just useful tools; they are crucial to the qualitative research. These questions impact the majority of the actions required to perform the study by describing exactly what the researcher is attempting to discover. In this context, the objective is to develop five research questions which will generate evidence to support the clinical usefulness of the test and its introduction into the health care system.

The first research question could be:

“What is the effectiveness of the imaging test and differences in clinical progression of rheumatoid arthritis?’”

The second research question could be:

“What is the use of the imagining test in analyzing as a diagnostic and prognostic tool in rheumatoid arthritis?”

The third research question could be:

“What is the diagnostic accuracy of the imaging test or imaging assay for rheumatoid arthritis?”

The fourth research question could be:

“Is the diagnostic accuracy of the imaging test being more in comparison with other imaging test in measuring rheumatoid arthritis?”.

The fourth research question could be:

“A comparison of the diagnostic accuracy and prognostic value of the new imaging test for rheumatoid arthritis with older imaging test?”

These clinical research questions would help to determine the effectiveness of the newly developed imaging test as well as the prognostic value which will evaluate the accuracy of the test. In addition, the research question will help to compare to other imaging test which were used traditionally and an effective outcome might improve the efficacy of the new imaging test.

Reference

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