1. Risk stratification of acutely admitted medical patients Mikkel Brabrand October 20131

2. Challenges  No. 1 – Admissions  No. 2 – Staffing  Limited at best  Also internationally  No. 3 – Overcrowding  Too many patients  Universal problem October 20132 Statistics Denmark 2013

3. Consequences  Important decisions have to made by (inexperienced) staff under difficult and stressful working conditions  Diagnoses  Treatment  Disposition  Even resuscitation October 20133

4. Risk stratification or perhaps better known as prognostication October 20134

5. Methods of risk stratification Clinical assessmentBiochemical analysesClinical scores Most of the existing systems are of suboptimal quality 1 1 Brabrand et al. Scand J Trauma Resusc Emerg Med 2010 October 20135

6. Predictions by nursing staff  Prediction made in 1820 (63.9 %) admissions  Calibration in the large  3.1 % vs. 4.7 % Experienc e Discriminatio n Goodness of fit Overall0.823p<0.0001 <5 years0.728p<0.0001 5–9 years0.774p=0.002 10–14 years0.886p=0.13 ≥15 years0.874p=0.035 October 20136

7. Predictions by physicians  Prediction made in 734 (25.8 %) admissions  Calibration in the large  2.9 % vs. 5.8 % Experienc e Discriminatio n Goodness of fit Overall0.761p<0.0001 <5 years0.748p=0.0002 5–9 years0.955p=0.25 10–14 years0.739p=0.21 ≥15 years0.846p=0.07 October 20137

8. Agreement by both parties  507 (17.8 %) admissions assessed  Agreement (± 5 %) on 385 (75.9 %)  Calibration in the large  1.0 % vs. 2.1 %  Discriminatory power 0.898  Goodness of fit, p = 0.91 October 20138

9. Biochemistry Study 2 Prognostication using blood tests October 20139

10. Included systems VariablePrytherch scoreFroom scoreLoekito scoreAsadollahi score Lactate dehydrogenase  Bilirubin  Alkaline phosphatase  Bicarbonate  Alanine aminotransferase  Neutrophil count proportion  Urea/creatinine  Urea  Albumin  Platelets  Glucose   White cell count   Creatinine  Potassium  Sodium   Hemoglobin   Hematocrit  Age  Gender  Mode of admission  EndpointIn-hospital mortality Imminent deathIn-hospital mortality October 201310

11. Biochemical scores Prytherch score, n = 2667 (87.6 %) Froom score, n = 606 (19.9 %) Loekito score, n = 358 (11.8 %) Asadollahi score, n = 2619 (86.0 %) Calibration in the large3.5 % vs. 12.5 %-2.2 % vs. 0.8 %- Goodness of fitP < 0.001-P = 0.0007- Discriminatory power0.8420.8620.9220.803 Calibration in the large3.7 % vs. 3.7 %-2.8 % vs. 2.8 %- Goodness of fit – development P = 0.59P = 0.93P = 0.79 Discriminatory power – development 0.8580.9300.9110.808 Goodness of fit – validation P = 0.66P = 0.009P = 1.00P = 0.47 Discriminatory power – validation 0.8740.8820.9170.813 October 201311

12. Novel clinical score Study 3 Development and validation of a novel clinical score October 201312

13. Development of the models Univariable analyses 25 % cutoff Multivariable logistic regression 5 % cutoff Interaction? Deviation from linearity? Full model Simple model 1. Blood pressure 2. Heart rate 3. Respiratory rate 4. Age 5. Temperature 6. Level of consciousness 7. Oxygen saturation 8. Glucose 9. Loss of independence October 201313

14. Full model CoefficientsOdds ratios Systolic blood Pressure, mmHg -0.025 - per 100.78 Age, years0.024 - per 101.28 Respiratory rate, breaths/min 0.042 - per 51.23 Loss of Independence1.64.96 SaO 2 /FiO 2, %/100-0.0044 - per 500.80 Intercept-2.2 Systolic blood pressure SaO 2 /FiO 2 Age Loss of independence Respiratory rate Level of consciousness Systolic blood PressureSaO 2 /FiO 2 AgeLoss of Independence Respiratory rate Level of consciousness Glucose, temperature and heart rate October 201314

15. Performance of the full model Development cohort, n = 1984 (65.1 %) 1 st validation cohort n = 2261 (79.4 %) 2 nd validation cohort n = 1966 (76.8 %) Calibration in the large2.5 % vs. 2.4 %1.7 % vs. 1.8 %4.0 % vs. 3.2 % Goodness of fitP = 0.97P = 0.75P = 0.33 Discriminatory power0.870.900.88 October 201315

16. PARIS score Cutoff Systolic blood Pressure≤ 115 mmHg Age≥ 80 years Respiratory rate≥ 25 breaths/min Loss of IndependenceYes Peripheral oxygen Saturation≤ 93 % or any supplemental oxygen (FiO 2 > 21%) Risk = exp(-2.2 – 0.025 * sbp + 0.024 * age + 0.042 * rr + 1.6 * loi – 0.0044 * sao 2 /fio 2 )/(1+exp(-2.2 – 0.025 * sbp + 0.024 * age + 0.042 * rr + 1.6 * loi – 0.0044 * sao 2 /fio 2 )) October 201316

17. Performance of the PARIS score Development cohort, n = 1984 (65.1 %) 1 st validation cohort n = 2261 (79.4 %) 2 nd validation cohort n = 1966 (76.8 %) Calibration in the large --- Goodness of fitP = 0.42P = 0.74P < 0.001 Discriminatory power0.860.870.86 October 201317

18. External validation  John Kellett has tested the PARIS score  Ireland  AUROC 0.803  Goodness of fit p = 0.08  Uganda  AUROC 0.714  Goodness of fit p = 0.27 November 2014 18

19. Where were we? 1 Brabrand et al. Scand J Trauma Resusc Emerg Med 2010  Most existing systems have been developed using inadequate methodology or have not been externally validated 1 October 201319

20. Where are we now? 1 Brabrand et al. Scand J Trauma Resusc Emerg Med 2010  Most existing systems have been developed using inadequate methodology or have not been externally validated 1  Use of biochemical scores have been externally validated  We have added a new clinical score (developed correctly)  We have added a new player to the field (staff)  So… Not that much further October 201320

21. Clinical implications of our findings October 201321

22. Use on individual patients Risk score (in-hospital mortality) 10.7 % PARIS score4 (≈20 % 7-day mortality) October 201322

23. Individual patients  Use of scoring systems on individual patients is problematic  Ethics committee of the American Society of Critical Care Medicine recommends against it October 201323

24. Efficacy of the scores  Clinical assessment  Good, but misses some  Biochemical scores  Good, can become better, but misses some  Clinical scores  Better, but misses some  How can we improve this? October 201324

25. Another alternative?  What if we combined a biochemical score, clinical assessment and the PARIS score?  Prytherch score ≥ 0.15  Risk predicted by nurse ≥ 0.15  PARIS score ≥ 3  None of approximately 1400 patients would be missed October 201325

26. Price?  ≈900 would be incorrectly identified as being at risk!  Sensitivity 100.0 %  Specificity 36.4 %  PPV 3.25 %  NPV 100.0 % October 201326

27. So, we are not there, yet! November 2014 27

28. Thank you!  They study has been financially supported by  Sydvestjysk Sygehus  Karola Jørgensens Forskningsfond  Edith og Vagn Hedegaard Jensens Fond  AB Fonden  Johs. M. Klein og Hustrus Mindelegat  Thank you for all the assistance  Staff of Sydvestjysk Sygehus and Odense University Hospital, Jesper and Torben, Birte, Anni, Annmarie and Ida  And all those I have forgotten to thank! October 201328

29. Please be careful out there! October 201329