Diagnosis Διάγνωσις . Agostino Colli Gargnano April 4-8 2017

uncertainty DIAGNOSIS patient: iatrotropic stimulus: “Why did you decide to go to the doctor at this particular time? * clinical history symptoms physical examination signs Tests clinical decision : treatment no treatment further tests DIAGNOSIS *Feinstein AR Clinical Judgement Williams & Wilkins Baltimore1967

a binary concept You either have a certain disease or you do not. Differential diagnosis : considering a list of possible diseases A,B,C,D… deciding that the patient has the disease A but not B,C,D..

without disease with disease ….but diseases very often (if not always) are continuous, reflecting a range of severity, and that categorizing patients as either having or not having the disease depends on choosing a somewhat arbitrary cut-point of severity. Ann Intern Med. 2008;149:200-203 without disease with disease

a risk factor for advanced liver cancer and cancer–specific death binary category Most diseases : a continuous spectrum chronic hepatitis C /B primary biliary cirrhosis, primary scleosing cholangitis autoimmune hepatitis , alcoholic hepatitis , hepatocellular carcinoma: a judgment call as to the stage of the carcinogenic process that we think is severe enough. a risk factor for advanced liver cancer and cancer–specific death

uncertainty illness DIAGNOSIS DISEASE Translation history (symptoms) physical examination (signs) tests DIAGNOSIS DISEASE

NOSOGRAPHY : systematic description and classification (taxonomy) of diseases. The definition and taxonomy of diseases is based mainly on pathophysiological or historical criteria. “Diseases are distinguished from each other either by such alterations in the organs themselves, or their secretions, as can be ascertained by the senses of the observer (physical signs); or by changes in the functions of the parts affected (symptoms).” Oxford English Dictionary 1869 symptoms → syndrome signs→ disease When does or should a collection of signs and/or symptoms constitute a disease?

OVERLAP OF DISEASES DISEASE: a continous spectrum of severity biological factors clinical factors social influences Ann Intern Med 2001;134(9_Part_2):803-808 OVERLAP OF DISEASES

uncertainty illness DISEASE DIAGNOSIS Translation history (symptoms) physical examination ( signs) tests DISEASE DIAGNOSIS thinking about disease in terms of risk prediction is often superior to thinking about disease in terms of diagnosis.

decision to take or withhold an action

inreducible uncertainty : about the true state of the patient about the meaning of test result about the effectiveness of possible treatments To deal with the inherent uncertainty of daily clinical practice, physicians need to use a probabilistic approach and to link diagnosis and treatment in order to support their decisions

Medicine is a science of uncertainty and an art of probability William Osler 1849-1919 Medical care is the art of making decisions without adequate information Harold C Sox 1989

System 2 Analytic reasoning Analytic reasoning: activated when the physician faces a rare disease or an atypical presentation. Three characteristics of the analytic reasoning: 1. iterative: a step-by-step process, where hypotheses are generated or discarded at each step; 2. hypothetic-deductive: each hypothesis is used to predict what additional findings ought to be present if it is true; 3. probabilistic: the hypotheses are confirmed or dismissed by evaluating their probability, usually approximately Elstein AS 2002 Sox HC 1988 , 2007

pretest probability the probabability of the target disease before diagnostic tests result is known Subjective probabilities: psycological phenomena in the minds of those involved in the diagnostic at hands ideas perception eye brain

Pre-test probability= an OPINION about the likelihood that your patient actually is affected by the target disease judging by similarity and prevalence By prevalence Taking into account the frequency of the suspected diseases. Even with a typical presentation a rare disease remains rare (i.e. improbable) by similarity How much does your patient seem to have symptoms and signs (or also preliminary test results) typical of a suspected disease?

Judging by Prevalence Similarity Searching for a complication in patients with a well defined disease. The pre-test ≡ prevalence Es. diagnosing portal hypertension with esophafeal varices in patients with cirrhosis. The prevalence is about 50%, but is less in early detected cirrhosis. Similarity Compare the clinical pattern of a patient with the definition of a disease (illness script ) . Es secretory diarrhea , ipokaliemia, hypotension suggest VIPoma (a neuro-endocrine tumour producing VIP). But it is extremely rare <1/1000000 Balancing the likelihood of your diagnostic hypotheses considering the correspondence to a typical pattern and the frequency in your clinical setting

post-test probability a subjective estimate (opinion) of how much an hypothesis is probable is needed to calculate the effect of new information Uncertainty DIAGNOSIS pre-test probability test result LR+ & LR- post-test probability Pre-test ODDS Post-test ODDS

The effect of new information on uncertainty can be assessed when uncertainty is expressed as a probability the bayesian rule

What level of probability (or of uncertainty) is enough TO DECIDE ? to decide an action (start treatment, stop testing, order new tests) you should know the effectiveness of treatment, the prognosis and the accuracy of tests for the diagnosis of the hypothesized disease.

More information are needed (further tests) Making a diagnosis RULING OUT RULING IN 0 % 100 % More information would not change the DECISION to act as the patient had or not the disease More information would not change the DECISION to act as the patient had or not the disease More information are needed (further tests) The acceptable level of UNCERTAINTY depends on the penalty for being wrong. It is better to treat false positive patients or to withhold treatment in false negative?

the penalty for being wrong It is better (or less worse) : ? to treat false positive patients to withhold treatment in false negative

the probability of having a diesease to decide one has to link diagnosis and treatment the probability of having a diesease the effect of treatment

Conclusions: Uncertainty is intrinsic to the practice of medicine. The true state of the patient must be inferred from imperfect cues (history, physical examination, diagnostic tests) Physicians have to translate an illness into a disease (making a diagnosis) Diagnosis is a binary concept ( yes/not), but diseases are a continuous spectrum A disease should be considered not in term of presence or absence but in terms of risk prediction ( diagnosis/prognosis) To cope with uncertainty and to make decisions without certain knowledge, physicians have to represent uncertainty as a probability. Diagnosis should be defined as the level of probability (uncertainty) at which is possible to decide (start treatment, stop testing, order further tests) The acceptable level of uncertainty (diagnosis) depends on the penalty for being wrong. It is better to treat false positive patients or to withhold treatment in false negative? Physician to make decisions have to link diagnosis/prognosis and treatment