Experiences of a medical statistician working in a SARS-designated hospital in S

Experiences of a medical statistician working in a SARS-designated hospital in S www.phwiki.com

Experiences of a medical statistician working in a SARS-designated hospital in S

Jones, Bill, Operations Manager has reference to this Academic Journal, PHwiki organized this Journal Experiences of a medical statistician working in a SARS-designated hospital in Singapore Arul Earnest MSc, DLSHTM, C.Stat School of Public Health, University of Sydney Overview This presentation will take you through some of the research projects on Severe Acute Respiratory Syndrome (SARS), that were undertaken in Tan Tock Seng Hospital (TTSH) during the recent outbreak in 2003 I worked in the hospital from 2000 to 2005, providing consultation in addition to collaborating with clinicians from various medical specialities During the SARS outbreak starting from March 2003, there were several important research projects that originated from TTSH Let’s look briefly at some of these projects that I have been personally involved in Initial stage of the outbreak Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient in addition to initial contacts. Hsu LY, Lee CC, Green JA, Ang B, Paton NI, Lee L, Villacian JS, Lim PL, Earnest A, Leo YS. Emerg Infect Dis. 2003 Jun;9(6):713-7. One of the first few case-studies published on SARS world-wide No fancy statistical methods used, instead the paper made use of simple descriptive results presented in an appropriate in addition to useful manner

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Initial stage of the outbreak Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient in addition to initial contacts. Hsu LY, Lee CC, Green JA, Ang B, Paton NI, Lee L, Villacian JS, Lim PL, Earnest A, Leo YS. Emerg Infect Dis. 2003 Jun;9(6):713-7. Initial stage of the outbreak Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient in addition to initial contacts. Hsu LY, Lee CC, Green JA, Ang B, Paton NI, Lee L, Villacian JS, Lim PL, Earnest A, Leo YS. Emerg Infect Dis. 2003 Jun;9(6):713-7. Initial stage of the outbreak Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient in addition to initial contacts. Hsu LY, Lee CC, Green JA, Ang B, Paton NI, Lee L, Villacian JS, Lim PL, Earnest A, Leo YS. Emerg Infect Dis. 2003 Jun;9(6):713-7. Conclusions of study Initial clinical features of SARS are non-specific. Dry cough is common, although other symptoms of upper respiratory tract infection are unusual. Chest radiograph may be normal on week 1 of illness. In early stages, SARS may be hard to differentiate from other viral infections, in addition to diagnostic delays may contribute to the spread of the epidemic.

The next paper in JAMA Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. Lew TW, Kwek TK, Tai D, Earnest A, Loo S, Singh K, Kwan KM, Chan Y, Yim CF, Bek SL, Kor AC, Yap WS, Chelliah YR, Lai YC, Goh SK. JAMA. 2003 Jul 16;290(3):374-80. In as long as mative paper published in Journal of American Medical Association, a journal with a high impact factor Looked at the determinants of early/ intermediate recovery of SARS patients from the ICU OBJECTIVE: To describe the clinical spectrum in addition to outcomes of ALI/ARDS in patients with SARS-related critical illness. DESIGN, SETTING, AND PATIENTS: Retrospective case series of adult patients with probable SARS admitted to the intensive care unit (ICU) of a hospital in Singapore between March 6 in addition to June 6, 2003. MAIN OUTCOME MEASURES: The primary outcome measure was 28-day mortality after symptom onset. The next paper in JAMA The next paper in JAMA The characteristics of ICU in addition to non-ICU SARS patients were different: ICU patients were more likely to be older, less likely to be healthcare workers, likely to have shortness of breath, be on corticosteroids in addition to have several pre-existing comorbidities

The next paper in JAMA RESULTS: Of 199 patients hospitalized with SARS, 46 (23%) were admitted to the ICU Mortality at 28 days as long as the entire cohort was 20 (10.1%) of 199 in addition to as long as ICU patients was 17 (37%) of 46. Lower Acute Physiology in addition to Chronic Health Evaluation II scores in addition to higher baseline ratios of PaO2 to fraction of inspired oxygen were associated with earlier recovery. CONCLUSIONS: Critically ill patients with SARS in addition to ALI/ARDS had characteristic clinical findings, high rates of complications; in addition to high mortality. The next paper in JAMA Predictors of mortality among ICU patients Clinical features in addition to predictors as long as mortality in a designated national SARS ICU in Singapore. T ai DY, Lew TW, Loo S, Earnest A, Chen MI; Tan Tock Seng Hospital SARS ICU Group. Ann Acad Med Singapore. 2003 Sep;32(5 Suppl):S34-6. This time, the study examined the factors associated with mortality among ICU patients with SARS, using survival analysis techniques. i.e. the Cox regression model.

Predictors of mortality among ICU patients Clinical features in addition to predictors as long as mortality in a designated national SARS ICU in Singapore. T ai DY, Lew TW, Loo S, Earnest A, Chen MI; Tan Tock Seng Hospital SARS ICU Group. Ann Acad Med Singapore. 2003 Sep;32(5 Suppl):S34-6. Methods: Survival time was defined as the interval between date of illness in addition to death or censoring as of 9 June 2003. Following risk factors were studied: sex, age, race, co-morbidities, PaO2/FiO2 ratio on admission to ICU, lowest PaO2/FiO2 ratio, Acute Physiology in addition to Chronic Health Evaluation (APACHE) II score, highest serum lactate dehydrogenase (LDH), lowest serum sodium, lowest serum potassium, lowest absolute lymphocyte count (ALC), highest total white count (TWC), highest prothrombin time (PT) in addition to highest activated partial thromboplastin time (PTT). Univariate Cox regression models were fitted as long as each of the variables. Predictors of mortality among ICU patients Clinical features in addition to predictors as long as mortality in a designated national SARS ICU in Singapore. T ai DY, Lew TW, Loo S, Earnest A, Chen MI; Tan Tock Seng Hospital SARS ICU Group. Ann Acad Med Singapore. 2003 Sep;32(5 Suppl):S34-6. Methods: Starting from the most significant, variables that were significant in the univariate analysis were included in the multivariate model in turn. Likelihood ratio test was used to test whether inclusion of a new covariate helped improve the fit of the model. The Nelson-Aalen cumulative hazard plot (on the log scale) was used to graphically examine the proportional hazard assumption. The Schoenfeld test was used to as long as mally ascertain if the assumption of proportional hazards was violated as long as the final model. Predictors of mortality among ICU patients Clinical features in addition to predictors as long as mortality in a designated national SARS ICU in Singapore. T ai DY, Lew TW, Loo S, Earnest A, Chen MI; Tan Tock Seng Hospital SARS ICU Group. Ann Acad Med Singapore. 2003 Sep;32(5 Suppl):S34-6. Conclusion: About one in five probable SARS patients required ICU care. This group of critically ill SARS patients has high mortality in addition to morbidity. The predictors as long as ICU mortality were male gender, APACHE II score > 15 in addition to history of congestive cardiac failure. Wide CIs probably due to small number of CCF comorbidities

Evaluating the effectiveness of ribavirin Investigational use of ribavirin in the treatment of severe acute respiratory syndrome, Singapore, 2003. Leong HN, Ang B, Earnest A, Teoh C, Xu W, Leo YS. Trop Med Int Health. 2004 Aug;9(8):923-7. Objective: Ribavirin is a broad spectrum nucleoside analogue efficacious in the treatment of several viral infections. In the recent severe acute respiratory syndrome (SARS) outbreak, ribavirin was used in various countries against this novel coronavirus. We conducted a retrospective analysis to assess the efficacy of ribavirin in the treatment of SARS in Singapore. Methods: A total of 229 cases were analysed. Ninety-seven (42.4%) patients received ribavirin at a mean of 6.4 days of illness. Univariate analysis using Fisher’s exact test in addition to Student’s t-test. Multivariate analysis was per as long as med using Cox regression model with death as the outcome of interest. Evaluating the effectiveness of ribavirin Ribavirin prescribed in early stage of outbreak Evaluating the effectiveness of ribavirin Some clinical in addition to demographic differences found between those prescribed ribavirin in addition to those who were not. This is not surprising as the study was not an RCT

Evaluating the effectiveness of ribavirin Modelling was done sequentially to highlight the effect of the measured confounders on ribavirin’s effect on mortality. As we can see, there is a reversal in the direction of the effect of ribavirin, but the results were not significant, even though the numbers were not too small. Evaluating the effectiveness of ribavirin Investigational use of ribavirin in the treatment of severe acute respiratory syndrome, Singapore, 2003. Leong HN, Ang B, Earnest A, Teoh C, Xu W, Leo YS. Trop Med Int Health. 2004 Aug;9(8):923-7. Results: The treatment group had younger women with more symptoms of myalgia (P < 0.001). The crude death rate was 12.9% in the control in addition to 10.3% (P=0.679) in the treatment group. After correction as long as age, male sex, lactate dehydrogenase levels in addition to steroid use, the hazard ratio was 1.03 (95% CI: 0.44–2.41, P =0.939). Conclusion: In this retrospective, uncontrolled cohort analysis, use of ribavirin did not appear to confer any benefit as long as patients with SARS. Lung function among survivors of SARS Pulmonary function in addition to exercise capacity in survivors of severe acute respiratory syndrome. Ong KC, Ng AW, Lee LS, Kaw G, Kwek SK, Leow MK, Earnest A. Eur Respir J. 2004 Sep;24(3):436-42. Aims: To investigate pulmonary function in addition to exercise capacity in a group of survivors of the severe acute respiratory syndrome (SARS). At 3 months after hospital discharge, 46 survivors of SARS underwent the following evaluation: spirometry, static lung volumes in addition to carbon monoxide transfer factor (TL,CO). In total, 44 of these patients underwent cardiopulmonary exercise testing. Lung function among survivors of SARS Pulmonary function in addition to exercise capacity in survivors of severe acute respiratory syndrome. Ong KC, Ng AW, Lee LS, Kaw G, Kwek SK, Leow MK, Earnest A. Eur Respir J. 2004 Sep;24(3):436-42. Results: No abnormalities were detected in the pulmonary function tests in 23 (50%) of the patients. Abnormalities of as long as ced vital capacity (FVC), as long as ced expiratory volume in one second (FEV1), FEV1/FVC in addition to TL,CO were detected in seven (15%), 12 (26%), one (2%) in addition to 18 (39%) patients, respectively. All of these abnormalities were mild except in one case. In 18 patients (41%), the maximum aerobic capacity was below the lower limit of the normal range. Breathing reserve was low in four patients in addition to significant oxygen desaturation was detected in a further four patients. Haematological parameter changes in severe acute respiratory syndrome patients. Haematological parameters in severe acute respiratory syndrome. Chng WJ, Lai HC, Earnest A, Kuperan P. Clin Lab Haematol. 2005 Feb;27(1):15-20. Aims: We studied changes in haematological parameters in SARS patients using median values analysed according to the day of symptom onset. White cell (WCC), absolute neutrophil, absolute lymphocyte (ALC) in addition to platelet counts followed a v-shaped trend with the nadir at day 6 or 7 after symptom onset except as long as ALC in the ICU group that had not reached the nadir by day 12. Haematological parameter changes in severe acute respiratory syndrome patients. By plotting the median values as long as each haematological parameter over a period of 12 days from symptom onset, time trends as long as changes to Hb, WCC, platelet count, ANC in addition to ALC were obtained (Figure 1). The Hb as long as both groups continued to fall during the first 12 days of illness (graph not shown). The WCC initially decreased, reaching a nadir at day 7 or 8 of illness. The median nadir WCC was 4 x 10(9(/l (range 2–12 x 10(9)/l as long as non-ICU in addition to 2–14.5 x 10(9)/l as long as ICU group) as long as both groups. Changes in the ANC reflected changes in the WCC. The median nadir ANC was 2.66 x 10(9)/l (range 1.08–8.85 x 10(9)/l) as long as the non-ICU group in addition to higher as long as the ICU group at 2.8 x 10(9)/l (range 1.29–12.7 x 10(9)/l). Jones, Bill WHHY-FM Operations Manager www.phwiki.com

Differentiating SARS in addition to Dengue Use of simple laboratory features to distinguish the early stage of severe acute respiratory syndrome from dengue fever. Wilder-Smith A, Earnest A, Paton NI. Clin Infect Dis. 2004 Dec 15;39(12):1818-23. Epub 2004 Nov 19. BACKGROUND: The diagnosis of severe acute respiratory syndrome (SARS) is difficult early in the illness, because its presentation resembles that of other non-specific viral fevers, such as dengue. Dengue fever is endemic in many of the countries in which the large SARS outbreaks occurred in early 2003. Misdiagnosis may have serious public health consequences. We aimed to determine simple laboratory features to differentiate SARS from dengue. METHODS: We compared the laboratory features of 55 adult patients with SARS at presentation (who were all admitted be as long as e radiological changes had occurred) in addition to 147 patients with dengue. Features independently predictive of dengue were modeled by multivariate logistic regression to create a diagnostic tool with 100% specificity as long as dengue. Differentiating SARS in addition to Dengue Use of simple laboratory features to distinguish the early stage of severe acute respiratory syndrome from dengue fever. Wilder-Smith A, Earnest A, Paton NI. Clin Infect Dis. 2004 Dec 15;39(12):1818-23. Epub 2004 Nov 19. RESULTS: Multivariate analysis identified 3 laboratory features that together are highly predictive of a diagnosis of dengue in addition to able to rule out the possibility of SARS Platelet count of <140 x 10(9) platelets/L, white blood cell count of <5x10(9) cells/L, in addition to aspartate aminotransferase level of >34 IU/L. A combination of these parameters has a sensitivity of 75% in addition to a specificity of 100%. CONCLUSIONS: Simple laboratory data may be helpful as long as the diagnosis of disease in adults admitted because of fever in areas in which dengue is endemic when the diagnosis of SARS needs to be excluded. Application of this in as long as mation may help to optimize the use of isolation rooms as long as patients presenting with nonspecific fever. Differentiating SARS in addition to Dengue Several covariates were identified as significantly different between dengue in addition to SARS in the univariate analysis. However, many of these variables are related to one another (confounders)

Differentiating SARS in addition to Dengue A model with the combination of these 3 parameters in addition to using these cutoff values identifies dengue correctly in 75% (sensitivity of 75%) in addition to rules out dengue in 100% (specificity of 100%) of cases. From a public health point of view, a specificity of 100% is desirable so that no case of SARS will be misdiagnosed as dengue, in addition to thus, the patient not be isolated, leading to secondary transmission. Modelling bed-occupancy during SARS Using autoregressive integrated moving average (ARIMA) models to predict in addition to monitor the number of beds occupied during a SARS outbreak in a tertiary hospital in Singapore. Earnest A, Chen MI, Ng D, Sin LY. BMC Health Serv Res. 2005 May 11;5(1):36. BACKGROUND: Apply autoregressive integrated moving average (ARIMA) models to make real-time predictions on the number of beds occupied in Tan Tock Seng Hospital, during the recent SARS outbreak. METHODS: This is a retrospective study design. Hospital admission in addition to occupancy data as long as isolation beds was collected from Tan Tock Seng hospital as long as the period 14th March 2003 to 31st May 2003. The main outcome measure was daily number of isolation beds occupied by SARS patients. Modelling bed-occupancy during SARS Using autoregressive integrated moving average (ARIMA) models to predict in addition to monitor the number of beds occupied during a SARS outbreak in a tertiary hospital in Singapore. Earnest A, Chen MI, Ng D, Sin LY. BMC Health Serv Res. 2005 May 11;5(1):36. METHODS: Among the covariates considered were daily number of people screened, daily number of people admitted (including observation, suspect in addition to probable cases) in addition to days from the most recent significant event discovery. We utilized the following strategy as long as the analysis. Firstly, we split the outbreak data into two. Data from 14th March to 21st April 2003 was used as long as model development. We used ARIMA models in an attempt to model the number of beds occupied.

Conclusions There were several important clinical in addition to public health questions about SARS that has been answered through research projects in TTSH Ample opportunities as long as biostatisticians to do research in a clinical setting during an outbreak of an infectious disease Proximity to front-line clinicians helps promote research Challenges in working with specialists from various fields in addition to in a time-pressed environment. i.e. need answers yesterday A biostatistician often facilitates multi-disciplinary research (e.g. working with an anaesthetist, respiratory in addition to infectious disease specialist together can spark research ideas)

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