Autopsies in HIV: still finding missed diagnoses after 20 years

1
Autopsies in HIV: still finding missed diagnoses after 20 years Background • Mortality has significantly fallen with the advent of HAART and chemoprophylaxis for opportunistic infections (OI). (Palella et al, Mocroft et al.) • Despite these interventions mortality remains in developed world cohorts. • Reasons for this include poor/variable adherence, late presentation, changing demographics, viral resistance. (Sabin et al.) • The causes include OI, co-infection with blood-borne viruses, haematologiacal malignancy and non-HIV aetiology. With HAART diversity of cause may be increasing. • Post-mortem remains a highly sensitive issue. • However, it can change cause of death or confirm it and ultimately could influence future clinical practice. • The regional Tropical and Infectious Diseases Unit at RLUH/UHA has looked after an HIV cohort of patients since the beginning of the pandemic. • We examined results of available post-mortem examinations over the last 20 years, 1983-2005. Aims • To determine: • The overall number of post-mortem examinations carried out between 1983-2005 as a proportion of deaths in out cohort. • Causes of death and change in pre- and post-mortem primary diagnosis. • Which and how many diagnoses were missed. Methods • A retrospective study of all patients known to have died in the Unit between 1983-2005. • Information was obtained from case notes and autopsy reports. Results • Data was available on 105 of the 115 known to have died between 1983 and 2005. • Age: – Median at diagnosis: 33.5 (range 21-65) – Median at death: 38 (range 24-69) • Sex: – Pre- 1996: Male 93.2% (69/74) Female 6.8% (5/74) – Post 1996: Male 51.5% (17/33) Female 48.5% (16/33) – Overall: Male 80.4% Female 18.7% 1 MBJ Beadsworth, 1 D Cohen, 1 L Ratcliffe, 1 N Jenkins, 2 W Taylor, 1 NJ Beeching 1 Tropical and Infectious Disease Unit, Royal Liverpool University Hospital (RLUH), Liverpool. 2 Department of Histopathology, University Hospital Aintree (UHA), Liverpool. • Ethnic origin: (n=107) White British 80.4% White other 1.9% Black African 12.1% Asian 0.9% South American 3.7% • Pre 1996 1.4% of deaths occurred in those of Black African origin. • Post 1996 39.3% of deaths occurred in those of Black African origin. Likely route of transmission of HIV: (n=107) MSM 56% Heterosexual 12% Sexual intercourse in Africa 18% IDU 9% Blood product 2% Other/Unknown 10% • Post-mortem was requested in 50.4% (n=54) of patients. • They were carried out in 38% (n=41). • Change in Primary cause of death was seen in 51.2% (21). • Of the total diagnoses 70.7% changed post-mortem. Missed Diagnoses • No significant changes in diagnoses pre and post mortem were seen. • However: – Lymphoma was over-diagnosed (4 pre-mortem, 1 post-mortem). • CMV diagnosis was missed in 8 of 11 patients. • TB was missed in 3 patients and opportunistic mycobacterial infection in 1. • KS was missed in 3 of 4 patients. • Pneumonia was the commonest cause pre- and post mortem. 29% 37% 17% 15% 2% 0% OI Pneumonia Other Unknown Encephalopathy TB Pre-mortem diagnosis (n = 41) 18% 34% 32% 0% 5% 11% OI Pneumonia Other Unknown Encephalopath TB Post-mortem diagnosis (n = 41) Pre-mortem overall diagnoses (n = 57) Post-mortem overall diagnoses (n = 80) 43% 21% 15% 8% 6% 7% OI Pneumonia Other Unknown Encephalopath TB OI Pre-mortem % (n = 41) PCP 10 (4) Crypto 5 (2) CMV 2 (1) Toxo 2 (1) Lymphoma 10 (4) KS 0 (0) OI Post-mortem % (n = 41) PCP 7 (3) Crypto 0 (0) CMV 5 (2) Toxo 2 (1) Lymphoma 2 (1) KS 2 (1) OI (total) Pre- mortem % (n = 57) PCP 7 (4) Crypto 5 (3) CMV 5 (3) Toxo 5 (3) Lymphoma 11 (6) KS 2 (1) 35% 27% 20% 11% 7% 0% OI Pneumonia Other Unknown Encephalopath TB OI (total) Post- mortem % (n = 80) PCP 4 (3) Crypto 4 (3) CMV 14 (11) Toxo 5 (4) Lymphoma 6 (5) KS 5 (4) Number of Deaths of HIV Patients in Northwest England Conclusions Post-mortem remains a vital tool of investigation. It should and can be considered in every HIV positive patient who dies. Causes of death changed for the majority undergoing post-mortem. Current diagnostic tools are inadequate. Results cont. References Palella et al. New Eng J Med 1998; 338. Mocroft et al. Lancet 2003; 362. Sabin et al. AIDS 2006;20. 98 87 43 38 37 30 30 28 23 36 0 20 40 60 80 100 120 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 Year Year

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Autopsies in HIV: still finding missed diagnoses after 20 years. 1 MBJ Beadsworth, 1 D Cohen, 1 L Ratcliffe, 1 N Jenkins, 2 W Taylor, 1 NJ Beeching 1 Tropical and Infectious Disease Unit, Royal Liverpool University Hospital (RLUH), Liverpool. - PowerPoint PPT Presentation

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Autopsies in HIV: still finding missed diagnoses after 20 years

Background• Mortality has significantly fallen with the advent of HAART and

chemoprophylaxis for opportunistic infections (OI). (Palella et al, Mocroft et al.)

• Despite these interventions mortality remains in developed world cohorts.

• Reasons for this include poor/variable adherence, late presentation, changing demographics, viral resistance. (Sabin et al.)

• The causes include OI, co-infection with blood-borne viruses, haematologiacal malignancy and non-HIV aetiology. With HAART diversity of cause may be increasing.

• Post-mortem remains a highly sensitive issue.

• However, it can change cause of death or confirm it and ultimately could influence future clinical practice.

• The regional Tropical and Infectious Diseases Unit at RLUH/UHA has looked after an HIV cohort of patients since the beginning of the pandemic.

• We examined results of available post-mortem examinations over the last 20 years, 1983-2005.

Aims• To determine:

• The overall number of post-mortem examinations carried out between 1983-2005 as a proportion of deaths in out cohort.

• Causes of death and change in pre- and post-mortem primary diagnosis.

• Which and how many diagnoses were missed.

Methods• A retrospective study of all patients known to have died in the Unit

between 1983-2005.

• Information was obtained from case notes and autopsy reports.

Results• Data was available on 105 of the 115 known to have died between

1983 and 2005.

• Age:– Median at diagnosis: 33.5 (range 21-65)

– Median at death: 38 (range 24-69)

• Sex:– Pre- 1996: Male 93.2% (69/74) Female 6.8% (5/74)

– Post 1996: Male 51.5% (17/33) Female 48.5% (16/33)

– Overall: Male 80.4% Female 18.7%

1 MBJ Beadsworth, 1 D Cohen, 1 L Ratcliffe, 1 N Jenkins, 2 W Taylor, 1 NJ Beeching1 Tropical and Infectious Disease Unit, Royal Liverpool University Hospital (RLUH), Liverpool.

2 Department of Histopathology, University Hospital Aintree (UHA), Liverpool.

• Ethnic origin: (n=107)– White British 80.4%

– White other 1.9%

– Black African 12.1%

– Asian 0.9%

– South American 3.7%

• Pre 1996 1.4% of deaths occurred in those of Black African origin.

• Post 1996 39.3% of deaths occurred in those of Black African origin.

• Likely route of transmission of HIV: (n=107)– MSM 56%

– Heterosexual 12%

– Sexual intercourse in Africa 18%

– IDU 9%

– Blood product 2%

– Other/Unknown 10%

• Post-mortem was requested in 50.4% (n=54) of patients.

• They were carried out in 38% (n=41).

• Change in Primary cause of death was seen in 51.2% (21).

• Of the total diagnoses 70.7% changed post-mortem.

Missed Diagnoses• No significant changes in diagnoses pre and post mortem were seen.

• However:– Lymphoma was over-diagnosed (4 pre-mortem, 1 post-mortem).

• CMV diagnosis was missed in 8 of 11 patients.

• TB was missed in 3 patients and opportunistic mycobacterial infection in 1.

• KS was missed in 3 of 4 patients.

• Pneumonia was the commonest cause pre- and post mortem.

29%

37%

17%

15%

2%0%

OIPneumoniaOtherUnknownEncephalopathyTB

Pre-mortem diagnosis (n = 41)

18%

34%32%

0%

5%

11%

OIPneumoniaOtherUnknownEncephalopathyTB

Post-mortem diagnosis (n = 41)

Pre-mortem overall diagnoses (n = 57)

Post-mortem overall diagnoses (n = 80)

43%

21%

15%

8%

6%7%

OIPneumoniaOtherUnknownEncephalopathyTB

OI Pre-mortem % (n = 41)

PCP 10 (4)

Crypto 5 (2)

CMV 2 (1)

Toxo 2 (1)

Lymphoma 10 (4)

KS 0 (0)

OI Post-mortem % (n = 41)

PCP 7 (3)

Crypto 0 (0)

CMV 5 (2)

Toxo 2 (1)

Lymphoma 2 (1)

KS 2 (1)

OI (total) Pre-mortem % (n = 57)

PCP 7 (4)

Crypto 5 (3)

CMV 5 (3)

Toxo 5 (3)

Lymphoma 11 (6)

KS 2 (1)

35%

27%

20%

11%

7%0%

OIPneumoniaOtherUnknownEncephalopathyTB

OI (total) Post-mortem % (n = 80)

PCP 4 (3)

Crypto 4 (3)

CMV 14 (11)

Toxo 5 (4)

Lymphoma 6 (5)

KS 5 (4)

Number of Deaths of HIV Patients in Northwest England

Conclusions• Post-mortem remains a vital tool of investigation. • It should and can be considered in every HIV positive patient

who dies.• Causes of death changed for the majority undergoing post-

mortem.• Current diagnostic tools are inadequate.

Results cont.

References

Palella et al. New Eng J Med 1998; 338.

Mocroft et al. Lancet 2003; 362.

Sabin et al. AIDS 2006;20.

9887

4338 37

30 30 2823

36

0

20

40

60

80

100

120

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Year

Year