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Natural History of Disease Ahmed Mandil Prof of Epidemiology Family & Community Medicine Dept King Saud University Headlines Definitions Induction, incubation, latency CHD Natural history of disease Lead time Survival time May 24, 2017 Natural History of Disease 2 Phenomenon of disease: Natural history 1 • Disease is a process that unfolds over time • Natural history – sequence of developments from earliest pathological change to resolution of disease or death May 24, 2017 Natural History of Disease 3 Phenomenon of disease: Natural history 2 • Induction – time to disease initiation • Incubation – time to symptoms (infectious disease) • Latency – time to detection (for noninfectious disease) or to infectiousness May 24, 2017 Natural History of Disease 4 Phenomenon of disease: Natural history 3 • Induction – time to disease initiation • Incubation – time to symptoms (infectious disease) • Latency – time to detection (for noninfectious disease) or to infectiousness May 24, 2017 Natural History of Disease 5 Phenomenon of disease: Natural history 4 • Induction – time to disease initiation • Incubation – time to symptoms (infectious disease) • Latency – time to detection (for noninfectious disease) or to infectiousness May 24, 2017 Natural History of Disease 6 Natural History of Disease Detectable subclinical disease Susceptible Host Subclinical Disease Point of Exposure Clinical Disease Diagnosis sought Outcome: Stage of Recovery, Complications, Disability, or Death Onset of symptoms Screening 24 May 2017 Screening 7 Natural history is central to screening Detectable, preclinical Pre-detectable Age: 35 45 Possible detection via screening May 24, 2017 Disability or death Clinical 55 65 75 Clinical detection Natural History of Disease 8 Potential Methodological Issues Selection bias: Referral (voluntary) bias: volunteers being healthier, more compliant Length-biased sampling (prognostic selection): does screening selectively detect cases with better prognosis ? Lead-time bias: how earlier can diagnosis be made if the disease is detected by screening compared with usual timing of diagnosis if screening was NOT carried out ? Over-diagnosis bias: resulting in misclassification 24 May 2017 Screening 9 Survival time after diagnosis – lead time 1 Detectable, preclinical Pre-detectable Age: 35 45 Disability or death Clinical 55 65 75 Lead time Possible detection via screening May 24, 2017 Clinical detection Natural History of Disease 10 Survival time must increase > lead time 2 Clinical diagnosis & treatment Undetected (no screening) Pre-detectable Disability or death Survival time after diagnosis Early detect, diagnosis, & treatment Pre-detectable Monitoring for recurrence ? Lead time Age: 35 May 24, 2017 45 55 Natural History of Disease 65 75 11 Slowly progressing diseases are easier to detect by screening Clinical diagnosis, treatment Predetectable Disability or death Survival time after diagnosis Clinical diagnosis & treatment Detectable, pre-clinical Pre-detectable Disability or death Survival time after diagnosis Age: 35 May 24, 2017 45 55 65 Natural History of Disease 75 12 Natural history of coronary heart disease 1 “Spontaneous atherosclerosis” Chronic minimal injury (blood flow, CHL, smoking, infection?) (youth?) May 24, 2017 Fibrointimal lesion “Lipid lesion” Accumulation of lipids and monocytes, toxic products, platelet adhesion (adolescence) Plaque growth, occlusion Migration & Disruption proliferation of thrombi smooth muscle cells (adulthood) (adulthood) Natural History of Disease 13 Natural history of coronary heart disease 2 “Spontaneous atherosclerosis” Chronic minimal injury (blood flow, CHL, smoking, infection?) (youth?) May 24, 2017 Fibrointimal lesion “Lipid lesion” Accumulation of lipids and monocytes, toxic products, platelet adhesion (adolescence) Plaque growth, occlusion Migration & Disruption proliferation of thrombi smooth muscle cells (adulthood) (adulthood) Natural History of Disease 14 Natural history of coronary heart disease 3 “Spontaneous atherosclerosis” Chronic minimal injury (blood flow, CHL, smoking, infection?) (youth?) May 24, 2017 Fibrointimal lesion “Lipid lesion” Accumulation of lipids and monocytes, toxic products, platelet adhesion (adolescence) Plaque growth, occlusion Migration & Disruption proliferation of thrombi smooth muscle cells (adulthood) (adulthood) Natural History of Disease 15 References Raffle A, Gray M. Screening: Evidence and practice. Oxford: Oxford University Press, 2007 Gordis L. Epidemiology. Chapters 5, 18. 2009 Schoenbach VJ. Natural history of disease and population screening. Gillings School of Public Health. University of North Carolina – ChapelHill, USA. Weissfeld JL. Screening and early detection May 24, 2017 Natural History of Disease 16 Thank you for your kind attention May 24, 2017 Natural History of Disease 17