Association of Clinical Criteria and Computed Tomography Pulmonary Angiogram Findings in Patients Suspected to Have Pulmonary Embolism, Exams of Nursing

Download Association of Clinical Criteria and Computed Tomography Pulmonary Angiogram Findings in Patients Suspected to Have Pulmonary Embolism and more Exams Nursing in PDF only on Docsity! 1 ASSOCIATION OF CLINICAL CRITERIA AND COMPUTED TOMOGRAPHY PULMONARY ANGIOGRAM FINDINGS IN PATIENTS SUSPECTED TO HAVE PULMONARY EMBOLISM CKNOWLEDGEMENT First and foremost, my utmost gratitude goes to God Almighty for the gift of life and opportunity. I do thank my supervisors, Dr. Nelson Kimani and Dr. Christine Mamai for the guidance and advice right from the proposal formulation to the conclusion of the study. I thank you for the continuous encouragement. To all my colleagues in Kenyatta National Hospital who assisted in all possible ways during my study. Mr. Wycliffe Ayieko (statistician), thank you for your guidance and assistance. Last but not least, my spouse Zack and children - Zara and Zion who have been patient, accommodating and inspiring during this period. 2 ABBREVIATIONS AND ACRONYMS ALARA…...............................As Low As Reasonably Achievable ACR.......................................American College of Radiologists ANOVA…............................Analysis of Variance CAD........................................Coronary Artery Disease CTPA…...................................Computed tomography pulmonary angiography DRC........................................Democratic Republic of Congo DVT….....................................Deep venous thrombosis ESR.........................................European Society of Radiologists HIV…......................................Human Immunodeficiency Virus HRT….....................................Hormone Replacement Therapy KNH…....................................Kenyatta National Hospital NH...........................................Nairobi hospital NHIF.......................................National Hospital Insurance Fund PAD.......................................Peripheral arterial disease PE…........................................Pulmonary Embolism RESPECT-ED........................Rates of pulmonary emboli and subsegmental pulmonary emboli with modern computed tomograms in Emergency Departments RCR ...............................................Royal College of Radiologists SSPE…...................................Subsegmental pulmonary embolism USA…....................................United States of America VTE…....................................Venous Thrombo- Embolism 5 recommended level as outline by Royal College of Radiologists and comparable to similar studies in Africa. The knowledge gained will be useful in the development of clinical imaging guidelines for imaging in suspected PE. 6 CHAPTER 1 INTRODUCTION Pulmonary Embolism refers to embolic occlusion of the pulmonary arterial system. It poses a diagnostic challenge to clinicians because of its ambiguous and non-specific clinical presentation. PE, being an emergency condition, requires one to have high index of suspicion to allow for quick and accurate diagnosis. Prompt diagnosis is necessary because a patient with PE can easily end up as a mortality if not assessed in the right and timely way. On the downside the clinicians can easily end up over-investigating patients with any symptom suggesting PE. This has been shown in several studies, the CTPA as a diagnostic tool for PE has been overused 12(Smith et al., 2016; Wiener, Schwartz & Woloshin, 2011). Hence, a large percentage of patients sent for CTPA did not require it as evidenced by the lower than recommended yield rate of all CTPAs done. CTPA is a benchmark diagnostic test for PE. On the downside, it is costly, invasive, and not easily available in many medical centers, especially in a developing country (Wells et al., 1998)3. Cost of medical care in this region is a concern and there is a need to reduce the cost of care by prudent choices. To achieve this, medical practitioners need to refer patients for only those tests that will benefit them and by using guidelines that will reduce the chances of sending patients for unsuitable tests. The optimal approach to investigating suspected pulmonary embolism should combine clinical judgment, lab investigations and relevant imaging. Clinical judgment may lack standardization; hence the use of clinical prediction rules is key. Well’s criteria for instance has been validated and is based on readily available information. The criteria are used to conclude diagnosis as low, moderate, or high clinical probability of PE and a two-category scheme (PE 7 likely or unlikely) (Wells, 2013; Heit et al 2000)4. The Wells criteria used by most clinicians for the diagnosis of PE are suitable for the black population in this part of the world. Wells Criteria is an objective way to establish patients who have high or intermediate probability of having PE and therefore cut down on the number of the patients sent for unnecessary CTPAs. The purpose of this study is to ascertain the yield of the CTPAs investigating for PE done at a referral hospital in Nairobi and to check if the clinical criterion being used helps to correctly pick out patients likely to have PE. This would eventually contribute to the development of local diagnostic imaging guidelines for PE. The established association between these criterion and CTPA findings will also be a form of audit on whether the use of clinical scoring is used before the decision is made to do a CTPA. 10 Figure 1: The venous thrombi mainly originate in venous valve pockets and at other sites of apparent venous stasis. The thromboemboli travel through the venous system right side of the heart and to the pulmonary artery where it progressively narrows the vessel to total occlusion causing a VQ mismatch. The vascular bed beyond this point is deprived of profusion. Image retrieved from https://emedicine.medscape.com/article/300901-overview Patients with iliofemoral DVT may also have Virchow’s triad of thrombogenesis (Golan, Tashjian & Armstrong 2011)14. This consists of increased chances of coagulation, hemodynamic changes (stasis or turbulence), and endothelial injury or dysfunction. Such instances include long surgical operations, prolonged immobility during travel, varicose veins, endothelium trauma, pregnancy, and obesity among others. Clinical presentation of PE Signs and symptoms of PE are non-specific and largely depend on the size of the embolism and co-morbidity, hence, may escape prompt diagnosis. PE may be one of the most misdiagnosed conditions in many hospitals; patients with PE can also test negative during diagnosis. In many cases, PE is asymptomatic and is revealed incidentally during the diagnosis 11 of another disease, and worse still, during an autopsy. Only about 40% of the patients with VTE present with classic PE symptoms. PE symptoms include dyspnea (new or worsening) pain in the chest, or low blood pressure with no other cause (McRae, 2011)15. In most cases, during the diagnosis of PE, dyspnea is usually the first suspect symptom of PE, in addition to pre-syncope or syncope, chest pain, and haemoptysis (Stein & Henry, 1997; Morrone & Morrone, 2018)16 17. Though intermittent, shock and arterial hypotension are significant in the diagnosis as indicators of central PE or haemodynamic abnormality. Dyspnea in central PE may be acute and severe, while in Subsegmental Pulmonary Embolism (SSPE) it presents as mild and transient (Konstantinides et al, 2014)18. Among patients with pre-existing heart failure and pulmonary disease may only present with worsening dyspnoea. On the other hand, dyspnea may be absent even in patients with circulatory collapse (Stein et al, 2007)19. Dyspnea, Syncope and hypotension usually indicate massive PE while chest pain, cough and hemoptysis indicate a smaller and peripheral emboli present in patients with pulmonary infarction. Chest pain in PE is caused by pleural irritation resulting from distal emboli triggering pulmonary infarction. Central PE may clinically be confused with angina especially due to right ventricular ischaemia, or aortic dissection. Clinicians’ awareness of risk factors is crucial for more effective and efficient discernment of PE. The likelihood of a patient being positively diagnosed with PE is more when they have more predisposing factors (Anderson Jr. & Spencer, 2003)20. On the other hand, it is reported that no risk factors can be detected in more than a quarter of patients with PE (Stein et al, 2007). 12 Risk factors The diagnosis of PE has to be intentional for the disease to be detected. All tests for PE are specific to its symptoms and the physician has to discern the likelihood of the patient presenting PE to order for testing. This makes the PE very easy to miss, if its clinical presentation is vague. The awareness of the predisposing factors to PE is, therefore, crucial for one to increase their index of suspicion. Genetic factors that provoke PE include history of thrombi in the family, personal history of recurrent blood clots, and personal history of inexplicable miscarriages (Crous-Bou, Harrington & Kabrhel, 2016)21. Acquired risk factors include smoking, cancer, pregnancy, and hormonal contraception especially estrogen based and Hormonal Replacement Therapy (HRT), obesity and immobility due to illness or after surgery among others. Diseases that predispose patients to PE include atherosclerosis, diabetes, metabolic syndrome, atrial fibrillation, obesity, heart failure, vasculitis, DVT, peripheral artery disease (PAD). Other risk factors include use of medication such as Human Immunodefiency Virus (HIV) treatments and estrogen based contraceptives, pregnancy, increase homocysteine levels, smoking, dehydration, etc. Diabetes mellitus. Acute or chronic hyperglycemia triggers the coagulation cascade and the result is hypo fibrin development that causes PE (Demir et al., 2017)22. In addition, impaired glucose tolerance and stress hormones cause high blood sugar levels and present a risk factor for PE. Hence, the presence of diabetes mellitus increases the risk of developing PE. Pregnancy and HRT are among risk factors listed in the National Health Commission venous thromboembolism prophylaxis and treatment guide. Anatomical and physiological changes that occur during pregnancy increase PE risk and should be considered during diagnosis include hyper coagulopathy, development of thrombus, venous stasis, pressure on inferior vena 15 From the above algorithm, use of CTPA is indicated as a confirmatory test for all patients with high or intermediate probability and in the low probability where D dimer is positive. A CTPA currently costs 10,000 Kenyan Shillings (100 USD). This is way beyond the reach of many who present in the public hospitals especially considering that this is cost for a single test in patient that will require many other tests and that the test is required as an emergency. Hence why the clinician should be careful to request this test for only patients that require it Wells criteria is a scoring criteria used to decide on the highly suspicious patients depending on their clinical presentation of certain aspects of their medical history. The following table outlines the wells criteria. 16 D-dimer testing The plasma D-dimer enzyme-linked immunosorbent assay rises in the presence of PE due to plasmin’s breakdown of fibrin (Riley et al., 2016)25. D-dimer is a fibrin degradation product purposed to rule out thrombo-embolic disease in instances of low clinical probability. Related studies Qiao Ji did a retrospective study in China involving 551 patients diagnosed with PE in Hospital between 2012 and 2016 (Qiao Ji et al, 2017)26.They evaluated typical symptoms of PE in patients and their related predictors. They went ahead to correlate differentiated typical groups of patients with similar characteristics with their principal presentations of PE symptoms. They concluded that different symptoms were associated with different clustered clinical indicators and demographics among PE patients. This in my opinion would immensely help in narrowing down patients with a high likelihood of having PE and cut down on unnecessary CTPA studies. This information was also represented in a local retrospective study done by Ogeng’o. It studied 128 patients treated of PE from 2005 to 2009 (Ogeng’o et al. 2011). The currently proposed study seeks to update this information for the local cases. Rates of pulmonary emboli and subsegmental pulmonary emboli with modern computed tomograms in Emergency Departments (RESPECT-ED study, 2017)27 was a large study involving 7077 patients in 15 centers across Australasia region. It involved finding the rates of Pulmonary Emboli and sub segmental PE with modern CTPA in Emergency Department. It studied the yield of CTPA and correlated it with the factors that affect the yield. Significant yield was considered to be 15.4%, a previous determined rate by the Royal college of 17 Radiologists which was derived from analysis of previous studies on use of CTPA for diagnosis of PE in various centers (Kim, Hills and Beckert, 2013)28. 1028 CTPA studies out the total 7077 done were positive for PE, giving a yield of 14.6%. There is one previous study done in Kenya by Wainaina A in 2013 study - Patterns of findings in MDCTPA for suspected pulmonary embolism in Nairobi that reported the yield of CTPA to be 27.3 % (Wainaina et al, 2013)29. The proposed study sought to compare these with the current trends. She faced some limitations in her study then. The requesting doctors offered scanty information on the clinical presentation of the patients. So she was inadequately equipped to offer a comparison of the clinical scores to the CTPA findings. She also recommended that CTPAs should be carried out on patients with high probability of PE to avoid unnecessary CTPAs. The current study has sought to address the limitations that were encountered in the Wainaina study. Schissler published a study done in USA that concluded that there was an increase in number of CTPAs being done with no corresponding increase of clinically significant PE diagnosis (Schissler et al, 2015)30. This meant a larger portion of the population was being exposed to the examination unnecessarily. There is an emerging chance of the same issues raised being faced in the local environment because of the increasing access to CTPA services in Kenya. It is necessary to confirm or rule out the probability of increasing chances of CTPA overuse in PE workup. In 2012, Tambe et al published a study done in Cameroon to assess the incidence of PE in patients underwent CTPA for diagnosis of PE. The study had 37 patients and 12 (32.4%) of them were positive for PE (Tambe et al, 2012)31. Costa et al published a study in 2014 that sought to establish the yield of CTPA to exclude acute PE. This was done in the background of evidence suggesting overuse of CTPA to 20 This study also takes into account the attainment of the ALARA Principle for radiological protection management that prompts physicians and radiologists to be cognizant of the radiation exposure during radiological tests. Therefore one should limit the dose using the optimization principle that conditions all exposures to be kept As Low As Reasonably Achievable (ALARA) with socioeconomic factors being taken into account. Considering the ALARA, CTPA scans should only be conducted when there is a high index of suspicion. This should be facilitated by the availability of an effective diagnostic criterion for PE. It will overall reduce the cost of care and radiation exposure. This study is also working towards helping attain the vision and objectives of AFROSAFE, an African movement of radiation workers who have a common vision targeting radiation safety. Afrosafe targets to make radiation based imaging and other interventional procedures in Africa appropriate and safe. Patients suspected to have PE are diagnosed using CTPA in major hospitals in the country. CTPA is the preferred for diagnostic imaging in patients who have presenting signs and symptoms of PE. This scan provides high-resolution images that are accurate and less invasive when compared to pulmonary angiography, which was the 'gold standard' procedure earlier. However, the cost of medical care is still a challenge and many patients are not able to access CTPA, especially those who seek medical services from public hospitals. There are several studies done regarding PE in Kenya. But no study has sought to directly correlate clinical presentation and radiological findings. This will therefore form a baseline for further scientific studies, seek to add to the scientific knowledge available, and generally help improve on the state of health care in Kenya. 21 RESEARCH QUESTION How does the clinical criteria of PE diagnosis compare to the radiological –CTPA findings OBJECTIVES OF THE STUDY BROAD OBJECTIVE The main objective of this prospective analytic study is to determine the correlation of clinical presentation of pulmonary embolism and radiological findings on CTPA in patients suspected to have PE in a tertiary referral hospital. SPECIFIC OBJECTIVES The specific objectives of the study include: 1) To establish the yield of all CTPA tests done to rule out PE 2) To establish demographic patterns observed in PE 3) To compare the clinical scores and patterns of clinical presentation of patients who present for CTPA The secondary objective is: 1) Find alternative radiological diagnosis that may present on CTPA images negative for PE 22 CHAPTER 3 STUDY DESIGN AND RESEARCH METHODOLOGY STUDY DESIGN: This is a mainly prospective analytic study seeking to find out the yield of CTPA done to rule out PE and to co-relate the CTPA outcome with prevailing clinical presentation. STUDY AREA: The study was carried out at Kenyatta National Hospital, a public tertiary hospital that serves as the main referral hospital in the apex of the Kenyan public referral system. Its radiology department is well equipped to carry out CT scans. It has a 128 slice Siemens CT scanner and can be used to produce CTPA images of good diagnostic quality. The department serves a casualty department, various outpatient clinics and a1800 bed capacity divided into specialty wards. It has been carrying out an average of 10 CTPAs monthly. The department radiologists review all CTPAs before they are released to the primary doctor. STUDY POPULATION Subjects and data for the study were collected from the requests received at the radiology departments in the study center for CTPA to rule out pulmonary embolism SAMPLING METHOD AND RECRUITMENT PROCEDURE Consecutive and purposive sampling method was used to select the study participants who met the criteria. Consecutive sampling requires investigator to pick subjects for the study as they present in the study site at the convenience of the researcher as long as the sample size is attained. Purposive sampling is also known as selective sampling, it is purposive because the subjects chosen have to follow laid out inclusion criteria. 25 Study procedure Following approval from the hospital administration as well as the University of Nairobi Research Board in collaboration with the KNH Research and Ethics committee the researcher commenced the study. Upon assessment of the inclusion criteria into the study, the CTPA images were assessed and findings of all individual studies recorded. The patients’ demographic characteristics including age, sex, occupation, and co- morbidities were collected using a predesigned data collection tool. The clinical criteria to be assessed was according to Well’s criteria. This information would be collected from the requesting doctor with the permission of the patient or the next of kin where it applies. The data collected was analyzed to finally answer the research question. ETHICAL CONSIDERATIONS The following ethical 1) Only patients who give consent for their inclusion in the study were be included 2) The identities of all patients were not included in the research instruments as well as the findings data sheets/reports. Only participant numbers were used to allow for referral purposes. Questionnaires did not collect patient names and only hospital identification numbers to allow easy association of the clinical data with the radiological data. 26 3) The researcher only commenced with the study after receiving approval from the ethical committee of the concerned institutions 4) The results of the study were delivered to the participating facilities to assist in creating a database for future studies and reference to facilitate improvement in patient care. 5) After the study is finalized, the researcher will destroy all information which can be used to identify participants. 6) The study participants were recruited voluntarily. 7) The results will be shared with relevant policy making bodies to improve on appropriate utilization of CTPA in patients with acute chest syndrome. 27 CHAPTER 4 DATA MANAGEMENT DATA COLLECTION When the patient presented with their request for CTPA at the radiology department, the CTPA was carried out immediately because of the emergency nature of the examination. Informed consent was then taken from the patient or the next of kin thereafter. The CTPA was conducted with a Siemens 128 slice multidetector CT scanner. 60 -100ml of contrast was administered to the patients at a speed of 5ml/ sec. The contrast dose was determined by the weight of each patient. Scans with poorly opacified main or lobar pulmonary arteries were considered inadequate. The CTPA were reported and the findings together with the demographic data of the patient will be entered in the data collection tool (Appendix 2) after verification by the radiologist on duty. PE was concluded if there is a filling defect within the main pulmonary arteries of the lobar arteries. The clinical data required for Well’s scoring was collected either from the patients’ medical records or by clerking the patient and entered into the designed forms. For this study, data was collected during the allocated period between from December 2019 to April 2020. The survey method was used as the primary strategy for these data collection. This was combined with clinical findings which will be sought from the requesting doctor or the patients’ records where available. All the information was presented in the data collection tool – Appendix 2(one for each patient.) 30 the oldest of 95 years. The table below shows the distribution of the patients recruited into the study by age and sex. Table 2.1 showing the patient distribution by age and sex. The percentage constitution of each category is shown in brackets The CTPA yield (overall prevalence of PE) was 34% (35/103). The mean age for those with positive PE cases was 46.7 (SD=15.7) years, while the median age was 45.0 (IQR=21) years. The youngest was 19 years, and the oldest was 83 years. 31 Table 2. 2 Age distribution observed in PE Of the patients who had positive PE on CTPA, 14 (40%) were male and 21(60%) were female. The Wells Score categorized the patients as follows: Table 2. 3 Wells scoring of recruited patients Among the patients scored as low on Wells score the prevalence of PE was 17.6% (3/17), the intermediate scores had a PE prevalence of 37.5% (24/64) while the high Wells score group’s prevalence was 36.3% (8/22). These results have been presented in the table below. 32 Table 2. 4 CTPA findings as per the clinical stratification groups. (Comparison of the clinical scores and patterns of clinical presentation of patients who present for CTPA) Among the 103 patients, 70.9% (73) were female and 29.1% (30) were male. The total yield of 34 patients had 14 male and 20 female most falling in the 36-45 years age group in both male and female patients. In male, the predominant underlying predisposing factors were malignancy and immobilization due to history lower limb injury. In the female, the main underlying predisposing factors were history of recent delivery and malignancy. These and others were also the presented co-morbidities. Most frequent comorbidities included Malignancy (25.7%); DVT (25.7%); infections including HIV and pulmonary tuberculosis (8.8%); cardiovascular conditions including hypertension and heart failure (11.4%); post- surgery (11.4 %) and pueperium (5.7 %) and diabetes mellitus (2.9%). On the other hand there were alternative radiological findings in the negative CTPAs and additional findings found in the positive CTPAs done as represented in the following table. 35 to have PE was tachycardia 71.4% (25/35). On the other hand only 25.7 %( 9/35) had history of previous DVT or PE. Table 2 .7 Factors of Wells score against the CTPA outcome. Abbreviations: CI, confidence interval; DVT, deep venous thrombosis; min, minutes; no-PE, no pulmonary embolism; OR, odds ratio; OR adjusted, adjustment for each item of wells score; PE, pulmonary embolism; wks., weeks; %, percentage; N, number Those diagnosed with PE were more likely to present with the following components of the Wells score: ‘haemoptysis’, ‘PE as the most likely diagnosis’ and ‘history of cancer in the last 6 months’ which all have an odds ratio of 2.0, 2.0 and 1.9 respectively and even higher adjusted odds ratio. The p values (adjusted) are also showing significant values for ‘PE as the only diagnosis’ and ‘history of cancer in the last six months’. This means this two are most weighted values in the wells criteria in the sample population studied. (Table 2.7). For the patients who had negative CTPAs for PE (68), alternative diagnosis (as assessed clinically) to explain their symptoms included:- lung metastasis 14.7%(10/68), pulmonary 36 hypertension 7.4% (5/68) , Lung infections 6% (4/68), congestive cardiac failure 4%(3/68), sepsis 4% (3/68), Asthmatic attack 4%(3/68), COPD 4%(3/68) and other miscellaneous ones . A large percentage, 27.9 %( 19/68) had no direct attributable explanatory cause. Figure 5: Distribution of alternative clinical diagnosis in patients who had negative PE on CTPA Miscellaneous 28% no attributable cause 27.9% lung metastasis 14.7% pulmonary hypertension 7.4% lung infections 6% congestive cardiac failure 4% sepsis 4% asthmatic attack 4% COPD 4% 37 ILLUSTRATIONS OF SAMPLE CASES: Case 1: Figure 6: Patient with bilateral pulmonary metastasis, pleural thickening, mild pleural effusion, light carotid thrombus with left sided segmental pulmonary embolism. 40 Figure 9: Patient with Cancer of the Breast showing right sided malignant pleural effusion with ipsilateral atelectasis with mediastinal and hilar lymphadenopathy Case 6: Figure 10: Patient with negative PE with cardiomegaly 41 Case 7: Figure 11: Patient found to have left sided hilar lymphadenopathy with segmental atelectasis Case 8: Figure 12: Patient with findings of previously interstitial lung disease: bilateral ground glass opacification interspersed reticular & septal thickening, pulmonary emphysema with formation of bullae & traction bronchiectasis DISCUSSION 42 Age and sex distribution In this study, we find that PE was most predominant in the 36-45 years age group. This can be mostly attributed to the prevalence of the other predisposing factors like malignancy and use of hormonal contraception. The male: female ratio is 1:1.4. This is not far off from the ratio of 1: 1.13 reported by Ogeng’o. The female preponderance may be because of the above mentioned predisposing factors and also because women have a better health seeking behavior than men (a complete audit that includes both morbidity and mortality numbers (including those diagnosed during autopsy) may be better for this assessment. In comparison to an Argentinian study done by Barco et al35 and published in 2018, the overall male to female ratio was 1:1. Though when ages were stratified the largest group was also similar for patients with identified risk factors which were malignancy and use of hormonal contraception. The highest incidence occurred in the 40- 49 year age group. But they also noted in their groups that there was a higher incidence of pulmonary embolism in patients with unidentifiable risk factors in patients above 50 years. In my study the data collected was not adequate to compare these findings. Comorbidities Malignancy was one of the most frequent comorbid factors. This may be associated with the increasing prevalence of cancer in the country. In the Ogeng’o study, DVT was the most common co- morbidity. DVT was the other most frequent comorbidity at the same level with malignancy (25%).This was still the case in the same Ogeng’o study. The association of infective factors leading to PTE has increasingly reduced when compared to the same in this study (where it comprised of 23.4 % combined and now it is down to 8.8% combined). The other comorbid factors were diabetes mellitus, pueperium, fractures and stroke. This suggests that now the non- 45 ‘history of cancer in the last 6 months’ which all have an odds ratio of 2.0, 2.0 and 1.9 respectively and even higher adjusted odds ratio. The p values (adjusted) are also showing significant values for ‘PE as the only diagnosis’ and ‘history of cancer in the last six months’. This means this two are most weighted values in the wells criteria in the sample population studied. (Table 2.7). Though this may have happened, the Yield remains acceptable. This pattern of findings could help further cut down on potentially negative CTPAs. Although no correlation was done to associate the role of D dimer tests and deep venous Doppler ultrasounds in the decision making on CTPA requests, this has been found to be beneficial to this quest in other studies. It is important to note that out of all the patients, only one had intentionally documented Well score in their clinical notes. For the others the information was gathered from the clerking notes and filled up by clerking the patient to fill gaps whenever necessary. The most missed out criteria in the notes was hemoptysis which luckily was verifiable from the patient. This indicates that the clinicians more likely rely on subjective means to arrive at a high index of suspicion for PE than in objectively using a laid down algorithm/ guideline. For the patients who had negative CTPAs for PE (68), alternative diagnosis (as assessed clinically) to explain their symptoms included:- lung metastasis 14.7%(10/68), pulmonary hypertension 7.4% (5/68) , Lung infections 6% (4/68), congestive cardiac failure 4%(3/68), sepsis 4% (3/68), Asthmatic attack 4%(3/68), COPD 4%(3/68) and other miscellaneous ones . A large percentage, 27.9 %( 19/68) had no direct attributable explanatory cause. The yield in this study showed 34% which was within the suggested acceptable CTPA yield for PE by the Royal College of Radiologists (15.4 %-37.4%). The Table below shows yields found in various previous studies published within the last 5 years. 46 Table 3. 1 The table below shows yields found in various other studies published in the last 5 years. 36 37 38 According to a retrospective study done at Hutt hospital by Kennedy et al39 in which patients sample size was studied, the CTPA Yield was found to be 15% just below the RCR recommendation (15.4% -37.4%). The bulk of negative CTPAs fell in the groups with low Wells Score and intermediate Wells score. Furthermore the authors noted that only 12 % of the patients had a Wells score or Geneva score performed and documented. A significant number of patient falling in the low and intermediate groups did not have a correlating D Dimer test done to further cut down on patients with possibly a negative CTPA outcome. Though this study did not further find out the role of D dimer tests in pre CTPA patient stratification, I agree with them that clinical scores and D dimer testing can help avoid unnecessary CTPA scans while safely investigating for PE. This can be a good follow up study in our set up to see if appropriate use of D dimer tests will help further reduce the rate of negative CTPAs. This will help improve patient care by reducing waiting time for patients, cutting down on the burden on radiological services, improving the cost of health care and reducing radiation and potential contrast media side effects to patients. 47 CONCLUSION In conclusion the study demonstrated that the wells score is a criteria that can be used to find out the clinical probability of one having PE. Though its outcomes can be further improved by other adjunct tests like D dimers and lower limb Doppler among others LIMITATIONS: 1. The study limited itself to the utility of Wells score in decision making on PE management algorithm to decide on whether a patient requires a CTPA or not. A further study to combine utility of D dimer and bilateral pedal Doppler may give a better assessment. This may go ahead to improve the clinical criteria. 2. Being an observational study, bias could not be totally ruled out. 3. These results represented were from a single center which is also a teaching hospital and therefore cannot be assumed to be a representation of other centers in the Nairobi and Kenya 4. The sampling was done for patients who were already suspected to have PE and therefore it may not have been very reliable in determination the prevalence of PE in the general population. 5. The sample type was from the African population therefore the findings cannot be generalized for other ethnic groups present in Kenya. The sample size was small which also restricts generalizability of the results to a larger target group. 6. The correlational aspect of this study limits the generalizability to associations and it’s impossible to make many conclusions. 50 STUDY CLOSURE AND DISSEMINATION PLAN Having completed the study: 1. The findings have been presented before a panel in the University of Nairobi Radiology department 2. A completed manuscript has been submitted to a medical journal for publishing. 3. It will also be availed to the department of Diagnostic Imaging and Radiation Medicine as part of the conditions to be met for the successful completion of the Masters of Medicine in Diagnostic Imaging and Radiation Medicine. 51 RESEARCH BUDGET ITEM UNIT COST NUMBER TOTAL COST Ksh Research Assistants /Data Collection Clerks 5000 3 15000 Biostatician Fees 20000 Printing Research Proposal 5 (6 x30) 9000 Printing consent and Data collection Forms 5 100 500 pens 20 20 400 Airtime for calls and data 10000 10000 Transport 500 per week 16 8000 Printing Final report 5 (10x60) 3000 Miscellaneous 5000 Contingencies (10 % of total budget) 7090 TOTAL 77990 52 REFERENCES 1 Wang, R.C., Miglioretti, D.L., Marlow, E.C., Kwan, M.L., Theis, M.K., Bowles, E.J., Greenlee, R.T., Rahm, A.K., Stout, N.K., Weinmann, S. and Smith-Bindman, R., 2020. Trends in imaging for suspected pulmonary embolism across US health care systems, 2004 to 2016. JAMA network open, 3(11), pp.e2026930-e2026930. 2 Wiener, R.S., Schwartz, L.M. and Woloshin, S., 2011. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Archives of internal medicine, 171(9), pp.831-837. 3 Wells, P.S., Ginsberg, J.S., Anderson, D.R., Kearon, C., Gent, M., Turpie, A.G., Bormanis, J., Weitz, J., Chamberlain, M., Bowie, D. and Barnes, D., 1998. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Annals of internal medicine, 129(12), pp.997-1005. 4 Heit, J.A., Mohr, D.N., Silverstein, M.D., Petterson, T.M., O'Fallon, W.M. and Melton, L.J., 2000. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Archives of internal medicine, 160(6), pp.761-768. 5Cohen, A.T., Agnelli, G., Anderson, F.A., Arcelus, J.I., Bergqvist, D., Brecht, J.G., Greer, I.A., Heit, J.A., Hutchinson, J.L., Kakkar, A.K. and Mottier, D., 2007. Venous thromboembolism (VTE) in Europe. Thrombosis and haemostasis, 98(10), pp.756-764. 55 17 Morrone, D. and Morrone, V., 2018. Acute pulmonary embolism: focus on the clinical picture. Korean circulation journal, 48(5), pp.365-381. 18 Authors/Task Force Members, Konstantinides, S.V., Torbicki, A., Agnelli, G., Danchin, N., Fitzmaurice, D., Galiè, N., Gibbs, J.S.R., Huisman, M.V., Humbert, M. and Kucher, N., 2014. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) Endorsed by the European Respiratory Society (ERS). European heart journal, 35(43), pp.3033-3080. 19 Stein, P.D., Beemath, A., Matta, F., Weg, J.G., Yusen, R.D., Hales, C.A., Hull, R.D., Leeper Jr, K.V., Sostman, H.D., Tapson, V.F. and Buckley, J.D., 2007. Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. The American journal of medicine, 120(10), pp.871- 879. 20 Anderson Jr, F.A. and Spencer, F.A., 2003. Risk factors for venous thromboembolism. Circulation, 107(23_suppl_1), pp.I-9. 21 Crous-Bou, M., Harrington, L.B. and Kabrhel, C., 2016, November. Environmental and genetic risk factors associated with venous thromboembolism. In Seminars in thrombosis and hemostasis (Vol. 42, No. 08, pp. 808-820). Thieme Medical Publishers. 56 22 Demir, B., Oguzturk, H., Turtay, M.G., Çolak, C., Demir, N.K. and Gürbüz, Ş., 2017. Pulmonary embolism: single and multiple risk factors. Biomedical Research (0970-938X), 28(9). 23 Kim, H.J., Walcott-Sapp, S., Leggett, K., Bass, A., Adler, R.S., Pavlov, H. and Westrich, G.H., 2010. Detection of pulmonary embolism in the postoperative orthopedic patient using spiral CT scans. HSS Journal®, 6(1), pp.95-98. 24 Reid, R., Westhoff, C., Mansour, D., de Vries, C., Verhaeghe, J., Boschitsch, E., Gompel, A., Birhhäuser, M., Krepelka, P., Dulicek, P. and Iversen, O.E., 2010. Oral contraceptives and venous thromboembolism: consensus opinion from an international workshop held in Berlin, Germany in December 2009. The journal of family planning and reproductive health care, 36(3), pp.117-122. 25 Riley, R.S., Gilbert, A.R., Dalton, J.B., Pai, S. and McPherson, R.A., 2016. Widely used types and clinical applications of D-dimer assay. Laboratory medicine, 47(2), pp.90-102. 26 Ji, Q.Y., Wang, M.F., Su, C.M., Yang, Q.F., Feng, L.F., Zhao, L.Y., Fang, S.Y., Zhao, F.H. and Li, W.M., 2017. Clinical symptoms and related risk factors in pulmonary embolism patients and cluster analysis based on these symptoms. Scientific reports, 7(1), pp.1-9. 27 Mountain, D., Keijzers, G., Chu, K., Joseph, A., Read, C., Blecher, G., Furyk, J., Bharat, C., Velusamy, K., Munro, A. and Baker, K., 2017. Correction: RESPECT-ED: R ates of Pulmonary E mboli (PE) and S ub-Segmental PE with Modern C omputed T omographic 57 Pulmonary Angiograms in E mergency D epartments: A Multi-Center Observational Study Finds Significant Yield Variation, Uncorrelated with Use or Small PE Rates. Plos one, 12(8), p.e0184219. 28 Kim, B., Hills, M. and Beckert, L., 2013. The use of computed tomography of pulmonary angiogram in a district hospital. International Scholarly Research Notices, 2013. 29 Nduta, W.A., 2013. The pattern of findings on multidetector computed tomographic pulmonary angiography for suspected pulmonary embolism in Nairobi (Doctoral dissertation, University of Nairobi). 30 Schissler, A.J., Rozenshtein, A., Schluger, N.W. and Einstein, A.J., 2015. National trends in emergency room diagnosis of pulmonary embolism, 2001–2010: a cross-sectional study. Respiratory research, 16(1), pp.1-7. 31 Tambe, J., Moifo, B., Fongang, E., Guegang, E. and Juimo, A.G., 2012. Acute pulmonary embolism in the era of multi-detector CT: a reality in sub-Saharan Africa. BMC medical imaging, 12(1), pp.1-6. 32 Costa, A.F., Basseri, H., Sheikh, A., Stiell, I. and Dennie, C., 2014. The yield of CT pulmonary angiograms to exclude acute pulmonary embolism. Emergency radiology, 21(2), pp.133- 141. APPENDICES APPENDIX 1: PREVALENCE OF PE CASES IN KNH Source: KNH Health Information Department (18/06/2019) YEAR ALIVE DEAD TOTAL 2014 44 27 71 2015 53 16 69 2016 82 34 116 2017 52 21 73 2018 67 31 98 2019 ( Upto 18/06/2019 ) 46 14 60 66 APPENDIX 2 DATA COLLECTION SHEET CT SCAN NUMBER: HOSPITAL NUMBER: AGE: SEX: OCCUPATION: CO-MORBIDITIES: CLINICAL SIGNS OF DVT NO ALTERNATIVE DIAGNOSIS FOR PE HR>100BPM IMMOBILSATION FOR 3 OR MORE DAYS/ SURGERY IN THE LAST 4 WEEKS PREVIOUS DVT OR PE HEMOPTYSIS CURRENT MALIGNANCY OR TREAMENT IN THE LAST 6 MONTHSOR IN PALLIATIVE CARE TOTAL SCORE CTPA FINDING (PROXIMAL PE / SSPE /NO PE) 67 APPENDIX 3: CONSENT FORM FOR PARTICIPATION IN THE STUDY This consent has three parts: Participant information sheet; sharing information about the research Consent form for signing Statement by the researcher. PARTICIPANT INFORMATION SHEET Investigator’s statement. My name is Dr.Oline Loice Amunga, a postgraduate student at the University of Nairobi department of diagnostic imaging and radiation medicine .I am conducting a study to compare your physical complains and CTPA (CT Scan) results to show whether you have Pulmonary Embolism (blood clots in the lung blood vessels). I am requesting you to take part in the study. The purpose of this consent form is to help you decide whether you want to be included in the study or not. Please read through the form carefully. You are free to ask any questions about the study. The investigator will be available to answer any questions during the study. The investigator or her assistants will be available to answer any questions during the study or thereafter. Benefits What we learn from this study will help us understand this condition better and therefore in future be in a better position to diagnose it more efficiently Duration of study 6 months. Compensation You will not receive any compensation for participating in the study. You are free to choose whether or not to participate in the study. You will suffer neither penalties nor loss of any benefits for declining to participate in the study. Confidentiality If you agree to participate in the study, information from your examination will be kept strictly confidential and will only be used for the purpose of this study. Information obtained will be kept under lock and key and soft copy information will be password protected. No specific information of any participant will be revealed to any person without their permission in writing. Your names will not appear on any of the records used for this study. 70 APPENDIX 4: KIBALI CHA KUSHIRIKI KATIKA UTAFITI KAULI YA MTAFITI Jina langu ni Dr. Oline Loice Amunga, mwanafunzi wa uzamili katika Chuo Kikuu cha Nairobi idara ya radiologia na dawa mionzi. ( Idara ya ‘Xray’). Ninafanya utafiti amabo unalinganisha dalili za ugonjwa wako na matokeo ya CTPA (CT Scan) uliyotumwa na daktari wako ufanye. .Ningependa kukuomba ushiriki katika utafiti huu. Madhumuni ya fomu hii ya idhini ni kukusaidia kuamua kama unataka kushiriki katika utafiti huu au la. Tafadhali soma fomu hii kwa makini. Unao uhuru wa kuuliza maswali yoyote kuhusu utafiti.Mtafiti au wasaidizi wake wataweza kujibu maswali yoyote ambayo unayo wakati wa utafiti au baada ya hapo. FAIDA Utafiti huu utasaidia madkatari kuelewa kwa kina juu ya ugonjwa huu wa embolism ya mapafu. Kwa hivyo wataweza kuelewa njia bora zaidi ya kuuchunguza ugonjwa huu. FIDIA Hakuna malipo yoyote utakayopewa kwa kushiriki katika utafiti huu. HAKI YA KUKATAA AU KUJIONDOA KATIKA UTAFITI Uko na uhuru wa kuchagua kushiriki au kutoshiriki katika utafiti. Hautateseka au kunyimwa huduma unayohitaji kwa sababu ya kuchagua kutoshiriki katika utafiti huu. SIRI YA UTAFITI Taarifa zote na matokeo ya utafiti huu zitalindwa vilivyo na kuwekwa katika hali ya siri. Hakuna taarifa maalum ya mshiriki yeyote zitafafanuliwa kwa mtu yeyote bila ya idhini yako kwa maandishi.Majina yako hayataonekana kwenye kumbukumbu za utafiti huu. huu. MADHARA Hakuna madhara yanayotarajiwa kutokana na wewe kuchagua kushiriki katika utafitit FOMU YA KUIDHINISHA KUSHIRIKI KATIKA UTAFITI Mimi natoa dhibitisho kwamba daktari amenieleza vikamilifu kuhusu utafiti ambao kichwa chake kimetajwa hapo juu.Ninakiri kuwa pia nimepewa fursa ya kuuliza maswali kuhusu utafiti huu na nimeridhika na majibu niliyopewa na daktari/mtafiti msaidizi. Ninaelewa kwamba kushiriki katika utafiti huu ni kwa hiari yangu mwenyewe na sijalazimishwa. Natambua kwamba sitapokea fidia yoyote iwe fedha au vinginevyo, wala sitapokea matibabu yoyote ya upendeleo, takrima au tuzo kwa ajili yakushiriki kwangu katika utafiti huu. Naelewa kuwa taarifa zangu za kibinafsi zitakuwa siri. Ingawa hivyo taarifa kuhusu matokeo ya uchunguzi zitakazokusanywa wakatiwa utafiti huu zitaangaliwa na kuchambuliwa na mtafiti mkuu pamoja na wasimamizi wake pindi itakavyohitajika. Ninatoa idhini yangu kushiriki katika utafiti huu. 71 Sahihi ya mshiriki: Tarehe: DHIBITISHO LA MTAFITI/MTAFITI MSAIDIZI Ninadhibitisha ya kuwa nimemwelezea mshiriki mambo yafuatayo kuhusu utafiti huu; Kwamba kushiriki ni kwa hiari yake. Hakuna fidia yoyote itakayopeanwa kwa kushiriki katika utafiti. Mshiriki anaweza kubadili uamuzi wa kuendelea kushiriki katika utafiti huu bila ya kuadhiri huduma ya matibabu yake. Haki za mshiriki zitalindwa na habari zitakazotolewa na mshiriki zitawekwa siri wakati wote na zitatumika kwa ajili ya utafiti huu pekee yake Jina: Sahihi: Tarehe: Kwa maelezo zaidi unaweza kuwasiliana na mtafiti mkuu kupitia anwani ifuatayo: Dr. Oline Loice Amunga Idara ya Radiologia na Dawa Mionzi Chuo Kikuu cha Nairobi Sanduku la Posta 37441-00100 Nairobi. Nambari ya simu -0773745132 Au KNH-UoN-ERC secretariat Katibu wa Utafiti Chuo Kikuu cha Nairobi - Hospitali Kuu ya Kenyatta Sanduku la Posta 20723-00202 KNH Nairobi. Nambari ya simu: 72600-9 Fax: 725272 Barua pepe: UoNknherc@uonbi.ac.ke