Definitions

The following definitions of HIV associated diseases have to be used at all sites of the Swiss HIV Cohort Study. This allows a maximal comparability of the frequency of HIV associated diseases.

A patient is considered as having Aids if at least one of the diseases mentioned in category C has been diagnosed. In rare cases, an Aids defining disease can occur during the primary infection. In this situation, the patient is not considered as having Aids.

A patient is considered as being in stage B if at least one of the diseases mentioned in category B has been diagnosed. In some cases, such a disease can occur during the primary infection. In this situation, the patient is considered as being still in stage A.

For most of the diseases a relapse has to be declared (see SHCS diseases form). If there is no specific definition for a relapse the same criteria apply as for the first appearance of the disease.

2. CDC category A conditions

At the moment of registration, at least one diagnosis must be coded.

For the condition "asymptomatic" the date of the first documented positive HIV-test is recorded. If no former documented positive HIV-test is available, use the date of registration.

At the moment of registration, at least one diagnosis must be coded.

For the condition « no opportunistic disease so far », the data center introduces the most appropriate date (usually the date of registration).

2.1 Primary HIV infection (database code PRI)

Exposure to HIV within the last three months AND clinical documentation or history of signs and/or symptoms suggestive of acute retroviral syndrome (such as acute febrile mononucleosis like
syndrome with lymphadenopathy or rash or pharyngitis or aphthous ulceration or meningo
encephalitis or myalgia or hepatitis) AND a documented negative HIV antibody test within the last six months AND detectable HIV-RNA in serum or plasma.

Detectable p24 Antigen or HIV-RNA AND a negative or borderline HIV antibody test converting to
reactive.

Definition revised 14.6.02

2.2 Asymptomatic HIV infection (no opportunist disease up to a given date) (database code ASY)

Positive HIV antibody test (ELISA), confirmed by Western blot in a second blood sample,
WITHOUT persistent generalized lymphadenopathy or signs/symptoms of CDC category B or C events.

2.3 Persistent generalised lymphadenopathy (database code LYM)

Lymph nodes of >1cm diameter in at least two extrainguinal sites persisting for >3 months.

Definition revised 31.7.00

3. CDC Category B diagnoses

3.1 HIV related diseases and symptoms

3.1.1 HIV-related peripheral neuropathy (database code PNP)

Clinical signs and symptoms of peripheral neuropathy, with/without electrophysiological
documentation AND no evidence for another etiology.

3.1.2 HIV-related myelopathy (database code MYE)

Clinical signs and symptoms of myelopathy, with electrophysiological or radiological
documentation AND no evidence for another etiology.

3.1.3 Thrombocytopenia (database code ITP)

Thrombocytes <100 x 109/l, determined on two occasions at least a month apart AND no evidence for another etiology (e.g. infection, tumor, myelosuppressive drugs).

3.1.4 Primary pulmonary hypertension (database code PPH)

Elevation of systolic right ventricular pressure (RVSP) over right atrial pressure (RAP) of greater than 25 mmHg, measured by continuous wave Doppler echocardiography or pulmonary artery pressure (PAP) of greater than 20 mmHg, measured by right heart catheterisation AND exclusion of pulmonary emboli by lung perfusion scan (^99mTC macroaggregated albumin particles) or on autopsy AND exclusion of obstructive or restrictive pulmonary disease based on clinical examination and by pulmonary function tests AND normal left ventricular function AND no evidence of congenital or valvular heart disease, evaluated by two-dimensional echocardiography AND no history of use of anorectic agents.

3.1.5 Lymphoid interstitial pneumonia (database code LIP)

Definitive diagnosis by histology

3.1.6 Unexplained weight loss >10% (database code WLO)

Baseline weight is the first documented weight measured after the diagnosis of HIV infection. Weight loss % is calculated by averaging two similar weights on consecutive occasions during follow-up and comparing this mean to baseline.

3.1.7 Fever without infectious cause (database code FEV)

>14 consecutive days,

>15 days in 30 day period, with investigations done to explain fever being negative.

3.1.8 Diarrhea (database code DIA)

At least three stools of reduced consistency per day for >30 days without concurrent specific cause.

3.2 Protozoal and helmintic diseases

3.2.1 Microsporidiosis (database code MIC)

Definitive diagnosis by microscopy of stool, or from biopsy. Must have a reliable history of persistent diarrhea for >1 month.
DATE: from when diarrhea has persisted >1 month AND stool specimen taken with positive result.

3.2.2 Toxoplasmosis retinitis * (database code TOR)

Definitive: By typical appearance, AND Positive specific PCR from acqueous humor AND Responds to toxo. treatment.

Presumptive: By typical appearance, AND responds to toxo treatment (no CMV treatment at the same time).

* in the SHCS this diagnosis is considered as a C event

3.2.3 Visceral leishmaniasis (database code LEI)

Definitive diagnosis by histology/microscopy. Not from skin.

3.2.4 Extraintestinal strongyloidiasis (database code EIS)

Definitive diagnosis by microscopy or histology.

3.3 Fungal diseases

3.3.1 Oral candidiasis (database code STO)

Severe, florid, marked, plaques (pseudomembranous), extensive, involving palate, persistent OR recurrent. Include new diagnoses of pseudomembranous OR recurrent episodes of erythematous oral candidiasis, that are treated, AND No relation to concomitant OR previous antibiotic OR immunesuppressive therapy.

3.3.2 Vulvovaginal candidiasis (database code CVV)

Severe, florid, marked, plaques (pseudomembranous), persistent or recurrent. Include new diagnoses of pseudomembranous, or recurrent episodes of erythematous candidiasis, that are treated, AND no relation to concomitant or previous antibiotic or immunesuppressive therapy.

3.3.3 Aspergillosis (database code ASP)

Definitive diagnosis by culture of normally sterile site OR culture from sputum/BAL, AND histology of invasive aspergillosis

3.4 Bacterial diseases

3.4.1 Pelvic inflammatory disease (database code PID)

Clinical diagnosis with further evidence by laparoscopy or (vaginal) ultrasonography.

3.4.2 Nocardiosis (database code NOC)

Definitive diagnosis by culture.

3.4.3 Bacillary angiomatosis (database code BAN)

Definitive diagnosis by histology AND bacilli in modified silver stain or positive PCR-test for Bartonella henselae

Culture from tissue or blood.

3.4.4 Listeriosis (database code LIS)

By culture from blood, from CSF or from biopsy of normally sterile site,

by detection of antigen from CSF.

3.4.5 Rhodococcus equi disease (database code ROD)

Definitive diagnosis by culture.

3.5 Viral diseases

3.5.1 Unusual manifestation of herpes zoster : multidermatomal or relapse (database code HZO)

Involving at least two dermatomes (contiguous or discontiguous), or two distinct episodes.

3.5.2 Progressive outer retinal necrosis syndrome (database code POR)

Definitive: By typical appearance, AND Positive specific PCR from acqueous humor AND Responds to VZV treatment.

Presumptive: By typical appearance, AND Responds to VZV treatment

3.5.3 Oral hairy leukoplakia (database code OLP)

Extensive, marked, symptomatic or bilateral, or persistent.

3.6 Neoplastic diseases

3.6.1 Cervical dysplasia, carcinoma in situ (database code CDC)

Definitive diagnosis by histology. Include moderate or severe dysplasia or carcinoma in situ (CIN2 or 3).

3.6.2 Hodgkin's disease (database code MHO)

Definitive: By histology.

DATE: from date of biopsy or time of good evidence of the presence of a mass (by scan) which under biopsy shows Hodgkin's lymphoma. (Presumptive: not accepted).

4 CDC CATEGORY C diagnoses

4.1 HIV related syndromes

4.1.1 HIV wasting syndrome (database code WAS)

Presumptive:

Documented profound involuntary weight loss >10% from baseline. Baseline weight is weight at first consultation. Weight loss is calculated by averaging two similar weights on consecutive occasions during follow-up and comparing this mean to baseline PLUS either :
persistent diarrhea (at least three stools of reduced consistency per day for >30 days) OR :
fever for >30 days without concurrent specific cause (such as cancer, TB, MAC, specific cause of enteritis).

DATE: first date on which 1), 2) OR 1) + 3) exist together.
(Definitive not accepted)

4.1.2 HIV encephalopathy (database code DEM)

Presumptive: Clinical findings of disabling cognitive and/or motor dysfunction interfering with occupations or activities of daily living (not "depression" or psychosis) AND No condition other than HIV infection to explain the findings. (CSF examination or autopsy evidence helpful) AND
Must have had CT or MRI scan. (Definitive: not accepted)

DATE: from time of scan.

4.2 Protozoal diseases

4.2.1 Pneumocystis carinii pneumonia (database code PCP)

Definitive: By cytology/microscopy or histology

Presumptive:
a) IF ON PCP PROPHYLAXIS: History of dyspnea on exertion, or non-productive cough (within 3 months), AND Typical appearance of diffuse bilateral pulmonale infiltrate, AND No bronchoscopy done or negative bronchoscopy after having received at least one week of PCP treatment, AND No evidence of bacterial pneumonia, AND Responds to PCP treatment.

b) IF NOT ON PCP PROPHYLAXIS FOR AT LEAST TWO WEEKS & CD4 COUNT LESS THAN 200: History of dyspnea on exertion, or non-productive cough (within 3 months), AND CXR normal, atypical or typical for PCP, AND No bronchoscopy done or negative bronchoscopy after having received at least one week of PCP treatment, AND No evidence of bacterial pneumonia, AND Responds to PCP treatment.

DATE: from abnormal CXR (or start of treatment).

4.2.2 Extrapulmonary pneumocystis disease (database code EPD)*

Definitive: By histology/microscopy. (Presumptive: not accepted).
* This diagnosis used in the SHCS does not correspond to any of the CDC definitions.

4.2.3 Cerebral toxoplasmosis (database code TOX)

Definitive: By histology or cytology.

DATE: from date of biopsy.

Presumptive: Recent onset of focal neurological abnormality consistent with intracranial disease, or reduced level of consciousness, or headache AND CT or MRI scan evidence of at least one lesion having a mass effect or enhancing with contrast medium AND Responded to toxo. treatment (evidence from repeat scan and/or clinical improvement).

DATE: from time of scan.

4.2.4 Disseminated toxoplasmosis (database code TOD)*

Definitive: By histology or microscopy (not culture). There should be a concurrent illness consistent with the diagnosis. Can include lung. (Presumptive: not accepted).
* This diagnosis used in the SHCS does not correspond to any of the CDC definitions.

4.2.5 Cryptosporidiosis (database code SPO)

Definitive: 1) By stool microscopy or histology, AND 2) must have reliable history of persistent diarrhea for >1 month.

DATE: from when diarrhea has persisted >1 month AND stool specimen taken with positive result. (Presumptive: not accepted).

4.2.6 Isosporiasis (database code ISO)

Definitive: By microscopy of stool, AND Must have a reliable history of persistent diarrhea for >1 month.

DATE: from when diarrhea has persisted >1 month AND stool specimen taken with positive result.

4.3 Fungal diseases

4.3.1 Oesophageal candidiasis (database code ESO)

Definitive: Macroscopic inspection at endoscopy,
OR
Histology of biopsy,
OR
Cytology of specimen from the mucosal surface (NOT by culture, NOT by barium swallow alone).

Presumptive:

Recent onset of retrosternal pain/discomfort on swallowing (not nausea), AND
Oral candidiasis diagnosed as pseudomembranous candida on inspection, or diagnosed by microscopy of specimen from mucosal surface (not culture), or patient noted "oral candida", was familiar with the appearance (e.g., documented prior episodes) and patient started treatment before seeing a doctor, AND must respond to antifungal treatment.

DATE: from when 1 + 2 together.

(presumptive diagnosis are not accepted for 4.3.2 - 4.3.5)

4.3.2 Candidiasis of trachea, bronchi or lungs (database code CAN)

Definitive:
By macroscopic inspection at endoscopy,
OR
Histology of biopsy or cytology of specimen from mucosal surface. Not by culture.

4.3.3 Cryptococcal meningitis (database code COM)

Definitive: By microscopy, or detection of antigen, or culture from CSF.

4.3.4 Other disseminated cryptococcosis, extrapulmonary (database code COC)

Definitive: By histology of extrapulmonary tissue, microscopy, or detection of antigen, or culture (e.g., blood, not sputum), AND Must have concurrent illness consistent with the diagnosis.

4.3.5 Disseminated coccidioidomycosis (database code CCM)

Definitive: By microscopy, culture, or detection of antigen. Not from lungs, cervical or hilar lymph nodes.

4.3.6 Disseminated histoplasmosis (database code HIS)

Definitive: By microscopy, culture, or detection of antigen. Not from lungs, cervical or hilar lymph nodes.

4.4 Bacterial diseases

4.4.1 Pulmonary tuberculosis (database code TBC)

Definitive: By culture (not PCR)

Presumptive:
By showing acid-fast bacilli in sputum that is not confirmed by culture or PCR, AND must respond to specific treatment
OR
Suggestive infitrate on CXR, AND (ananmnestic exposure to TB, or positive PPD test), AND response to specific treatment

DATE: from specimen and CXR, respectively.

4.4.2 Extrapulmonary tuberculosis (database code TEX)

(If patient has concurrent pulmonary TB please code also TBC)

Definitive: By culture (not lung alone).

Presumptive:
By showing acid-fast bacilli in stool, blood, body fluid or tissue, or in histology of cervical or hilar lymph nodes, of a species not identified by culture, AND There is a concurrent definitive diagnosis of pulmonary TB
OR
Responds to standard TB treatment.

DATE: from specimen.

4.4.3 Disseminated mycobacterium avium intracellular complex disease (database code MAC)

Definitive: By culture (not by PCR) other than sputum, stool or skin AND Must have concurrent illness consistent with the diagnosis, e.g., weight loss, fever, diarrhea or anemia.

DATE: from specimen.

4.4.4a Mycobacterium kansasii disease (database code KAN)

Definitive: By culture (not by PCR) in sputum, urine or stool (at least two specimens), or in normally sterile body fluid or biopsy AND Must have concurrent illness consistent with the diagnosis, e.g., pulmonary infitration, weight loss.

DATE: from specimen.

4.4.4b Mycobacterium avium or kansasii disease (old database summary code MAK)

If sufficient information is available, this code should be replaced by MAC or KAN.

4.4.5 Mycobacterium genavense disease (database code GEN)

Definitive: By culture (not by PCR) in sputum, urine or stool (at least two specimens), or in normally sterile body fluid or biopsy AND Must have concurrent illness consistent with the diagnosis.

DATE: from specimen.

4.4.6a Disseminated mycobacterial disease other or indeterminate (database code MYC)

Definitive: By culture (not by PCR) other than sputum, stool or skin. Include species other than M. tuberculosis, M. avium complex, M. kansasii or M. genavense, AND Must have concurrent illness consistent with the diagnosis.

DATE: from specimen.

Presumptive: By showing acid-fast bacilli in stool, or normally sterile body fluid (not sputum alone), or biopsy (not skin or lungs) where species not identified by culture, AND Must have a concurrent illness consistent with the diagnosis, as above.

DATE: from specimen.

4.4.6b Other pulmonary mycobacterial diseases* (database code MYP)

Definitive: By culture (not by PCR). Include species other than M. tuberculosis, M. kansasii or M. genavense, AND Must have concurrent illness consistent with the diagnosis.

* This category of diseases used in the SHCS does not correspond to any of the CDC definitions.

4.4.7 Recurrent Salmonella septicemia (database code SAL)

Definitive: By blood culture, with history of previously treated blood-culture-confirmed Salmonella septicemia.

4.4.8 Recurrent bacterial pneumonia (database code BPN)

Definitive: Two episodes of bacterial pneumonia within the last twelve months.

DATE: from the time of onset of the second episode.
RELAPSE :Is considered as a relapse every following bacterial pneumonia.

4.5 Viral diseases

4.5.1 Chronic mucocutaneous Herpes Simplex ulceration (database code HSV)

Definitive: By culture, microscopy, or detection of antigen, AND Must have a reliable history of persistent ulceration for >1 month, NOT including recurrent ulceration.

Presumptive: 1) Must have a reliable history of persistent ulceration for >1 month, NOT including recurrent ulceration, AND Responds to standard treatment

4.5.2 Visceral herpes simplex disease (database code HSD)

Definitive:By culture, microscopy or detection of antigen with associated visceral disease
OR
Positive specific PCR from CSF or from acqueous humor with associated CNS or retinal disease. (Presumptive:not accepted).

4.5.3 CMV retinitis (database code RET)

Definitive: By typical appearance, AND Positive specific PCR from acqueous humor AND Responds to CMV treatment.

Presumptive: Characteristic appearance on ophthalmoscopic examination. (Discrete patches of retinal whitening with distinct borders speeding in a centrifugal manner, frequently associated with retinal vasculitis, hemorrhage and necrosis. Resolution of active disease leaves retinal scarring and atrophy with retinal pigment epithelial mottling).

DATE: from when clinician was sure of diagnosis.

4.5.4 Other CMV disease (database code CMV)

Definitive: By histology or cytology. Not liver, spleen, or lymph nodes. A positive culture alone from any site (except CSF) without histologic or cytologic evidence is not sufficient. (Presumptive : not accepted).

4.5.5 Progressive multifocal leukencephalopathy (database code PML)

Definitive: By histology (not PCR for JC virus).

Presumptive: Recent onset of neurological abnormality consistent with intracranial disease, AND CT or MRI evidence of lesion consistent with PML AND Lack of evidence for lymphoma, toxoplasmosis (response to treatment), or HIV encephalopathy. Evidence for JC virus not necessary.

4.6 Neoplastic diseases

4.6.1 Kaposi sarcoma (database code KSA)

Definitive: By histology

Presumptive: By characteristic gross appearance of erythematous or violaceous plaque-like lesion on skin or mucous membrane. A presumptive diagnosis should not be made by a clinician who has seen few cases of KSA.

DATE: From time clinician was sure of the diagnosis.

4.6.2 Non-Hodgkin's lymphoma (database code NHL)

Corresponds to the old diagnoses IML (immunoblastic lymphoma) and BUL (Burkitt lymphoma)

Definitive: By histology. (Presumptive: not accepted).

DATE: from date of biopsy or time of good evidence of the presence of a mass (by scan) which is later biopsied to show lymphoma.

4.6.3 Primary cerebral lymphoma (database code LOB)

Definitive: By histology.

Presumptive: Recent onset of focal neurological abnormality consistent with intracranial disease, or reduced level of consciousness AND CT or MRI scan evidence of a lesion or lesions having a mass effect, AND No response to toxo. treatment, AND No evidence for lymphoma outside the brain.

DATE: from time of scan.

4.6.4 Invasive cervical carcinoma (database code ICC)

Definitive: By histology. Not intraepithelial neoplasia (CIN) or carcinoma-in-situ. (Presumptive: not accepted).

4.7 Indeterminate intracranial lesions* (database code ILE)

Presumptive: Disease due to intracranial lesion(s) where the differential diagnosis is primary cerebral lymphoma, toxoplasmosis, PML or HIV encephalopathy (DEM) but evidence is not sufficient to satisfy the corresponding criteria. Must have abnormal CT or MRI scan. (Definitive: not accepted).

DATE: from time of scan.

* This category of diseases used in the SHCS does not correspond to any of the CDC definitions.

5. Date of HIV related diseases

In general, the date for a definitive diagnosis is determined by the date in which the pathological specimen could be identified. The date of a presumptive diagnosis is determined by the time of satisfying the (set of) corrersponding criteria.

If a presumptive diagnosis has been reported and for the same disease a definitive diagnosis is made later on (e.g. by a biopsy), the date of the diagnosis should not be changed.

A diagnosis can not be recorded in the database as both presumptive and definitive

6. CDC : AIDS-defining conditions Corresponding SHCS codes

CDC : AIDS-defining conditions ¹	Corresponding SHCS codes
Candidiasis of bronchi, trachea, or lungs	CAN
Candidiasis, esophageal	ESO
Cervical cancer, invasive	ICC
Coccidioidomycosis, disseminated or extrapulmonary	CCM
Cryptococcosis, extrapulmonary	COC, COM
Cryptosporidiosis, chornic intestinal (greater than 1 month's duration)	SPO
Cytomegalovirus disease (other than liver, spleen, or nodes	CMV
Cytomegalovirus retinitis (with loss of vision)	RET
Encephalopathy, HIV-related	DEM
Herpes simplex : chronic ulcer(s) (greater than 1 month's duration); or bronchitis, pneumonitis, or esophagitis	HSV, HSD
Histoplasmosis, disseminated or extrapulmonary	HIS
Isosporiasis, chronic intestinal ) (greater than 1 month's duration)	ISO
Kaposi's sarcoma	KSA
Lymphoma, Burkitt's (or equivalent term)	NHL
Lymphoma immunoblastic (or equivalent term)	NHL
Lymphoma, primary, of brain	LOB
Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary	MAC, KAN, MAK (old database code)
Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary)	TBC, TEX
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary	MYC, GEN
Pneumocystis carinii pneumonia	PCP
Pneumonia, recurrent	BPN
Progressive multifocal leukoencephalopathy	PML
Salmonella septicemia, recurrent	SAL
Toxoplasmosis of the brain	TOX
Wasting syndrome due to HIV	WAS

SHCS codes, which do not correspond to any of the CDC AIDS-defining conditions :

EPD Extrapulmonary pneumocystis disease often considered together with pneumocystis carinii pneumonia

TOD Disseminated toxoplasmosis often considered together with toxoplasmosis of the brain

ILE Indeterminate intracerebral lesions

SHCS codes, which does not correspond to any of the CDC category B diagnosis :

MYP Other pulmonary mycobacterial diseases

¹ CDC. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992;41 (no. RR-17)

7. Immune Reconstitution Inflammatory Syndrome (IRIS)

7.1 IRIS induced by antiretroviral therapy in case of adequately treated opportunistic disease

The patient had a diagnosis of an opportunistic disease which has been (or is still) adequately treated, and
Symptoms consistent with an infectious/inflammatory condition appearing within three months of a new antiretroviral therapy (first ART or change of a failing regimen), and
These symptoms can not be explained by a newly aquired infection, nor by the expected clinical course of a previously recognized infectious agent, nor by side effects of therapy.

The date of IRIS is introduced in the DISEASE form on the line of the respective opportunistic disease in the column IRIS. The date of IRIS is greater than the date of diagnosis (NEW-date).

7.2 IRIS unmasking prevalent sub-clinical opportunistic disease

Symptoms consistent with an infectious/inflammatory condition appear within three months of a newly started antiretroviral therapy (first ART or change of a failing regimen), and
Symptoms can be attributed to a new opportunistic disease and, according to the treating physician, can not be explained by a newly aquired infection but by unmasking of a subclinical opportunistic disease and can not be explained by side effects of therapy.

The date of IRIS is equal to the date of diagnosis (NEW-date). Both dates are introduced in the DISEASE form on the line of the respective opportunistic disease.

7.3 IRIS in the case of chronic viral hepatitis B or C

A hepatits flare up occurs within three months of a new antiretroviral therapy (first ART or change of a failing regimen), and
Can not be explained by a newly aquired infection or by the expected clinical course according to chronic hepatitis or by side effects of therapy according to the treating physician.

The date of IRIS is introduced in the DISEASE form on the corresponding field.

7.4 IRIS manifesting as autoimmune disorder

An autoimmune disorder occuring within three years of a new immunonologically successful antiretroviral therapy (first ART or change of a failing regimen).

The date of IRIS is introduced in the DISEASE form on one of the lines (autoimmune). The type of the autoimmune disorder is specified.

8. Non-Aids defining events

8.1 Non-Aids defining malignomas

Diagnosis of cancer (other than: AIDS defining (non-Hodgkin's lymphoma, Kaposi's sarcoma ), or invasive cervical cancer); and other than basal and squamous cell skin cancers):
A. In a pathology report that established the diagnosis.
B. In a hospital discharge summary or consultation note from the hospitalization or clinic visit during which the diagnosis was established.
C. In the absence of A or B: Strong suspicion of cancer supported by
(i) evidence from radiological or other imaging technique,
(ii) or biochemical assay

Confirmed malignancy: A or B; Probable: C

8.2 Cardiovascular events including vein diseases

8.2.1 Myocardial infarction

Acute myocardia infarction, definitive
i) definitive* electrocardiogram (ECG), or
ii) symptoms* together with probable* ECG and abnormal enzymes (or troponine)*, or
iii) typical symptoms*, abnormal enzymes* and ischaemic/non-codable/not available* ECG, or
iv) fatal cases with naked-eye appearance of fresh MI and/or recent coronary occlusion found at necropsy.

1 ECG typical
2 ECG probable and Enzymes elevated and Symptoms typical, atypical or not interpretable
3 ECG ischaemic, uncodable or not available and Enzymes elevated and Symptoms typical

Acute myocardial infarction, possible
Living patients with typical symptoms* whose ECG* and enzymes* do not place them as myocardial infarction and in whom there is no conclusive evidence for another diagnosis for the attack.

ECG any Enzymes any Symptoms typical

ECG typical The development in serial records of a diagnostic Q wave -AND/OR-an ST segment elevation lasting more than one day
ECG probable Evolution of repolarisation changes (ST-segment depression or elevation, T wave inversion)
Note: Unlike the criteria for definite ECG, the evolution in this class can go in either direction, that is the codes can get better or worse
ECG ischaemic Ischaemic abnormalities without evolution
Symptoms typical chest pain lasting for at least 20 minutes and no other pathology known which could explain these symptoms

8.2.2 Cerebral infarction

Definitive: Rapidly developed clinical signs of focal or global disturbance of cerebral function lasting more than 24 hours (unless interrupted by surgery or death), with no apparent cause other than a cardiovascular origin. Secondary stroke caused by trauma should be excluded.
The differentiation between infarction and haemorrhage should be based on results of cerebral scanning or necropsy.
Presumptive: Findings of cerebral scanning uncertain.

8.2.3 Cerebral hemorrhage

8.2.4 Deep vein thrombosis

Definitive: Confirmed by ultrasonography, or CT scan, or MRI, or venography.
Presumptive: Elevated D-dimer plus >3 points on the Wells Clinical Prediction Rule for deep venous thrombosis plus absence of alternative diagnosis.
Wells clinical prediction rule (1 point for each of the following):

Active cancer;
paralysis, paresis, or plaster immobilization of lower extremities;
recently bedridden for more than 3 days, or major surgery, within 4 weeks;
localized tenderness along distribution of the deep venous system;
entire leg swollen;
calf swelling by more than 3 cm when compared with the asymptomatic leg (measured 10 cm below tibial tuberosity):
pitting edema (greater in the symptomatic leg);
collateral superficial veins (non-varicose).

(Adapted from: Wells PS et al. Lancet 1997;350:1796)

8.2.5 Pulmonary embolism

Definitive: Symptoms compatible with pulmonary embolism plus confirmation by CT scan, or MRI, or angiography, or ventilation-üerfusion scintigraphy, or confirmed on autopsy.
Presumptive: Symptoms compatible with pulmonary embolism plus confirmation of deep venous thrombosis on venography or ultrasound or other imaging studies and exclusion of an alternative etiology for the cardio-pulmonary symptoms.

8.3 Metabolic events

8.3.1 Diabetes mellitus

fasting plasma glucose > 7 mmol /l (fasting means > 8 hours without caloric intake) or
typical symptoms, plasma glucose > 11.1mmol/l or
venous plasma glucose > 11.1 mmol/l, 2 hours after oral intake of 75g glucose.

8.4 Liver-related events

8.4.1 Bleeding from gastric or esophageal varices

Endoscopy verified.

8.4.2 Spontaneous bacterial peritonitis

Detection of leukocytes in ascites, and no clinical evidence of secondary peritonitis.

8.4.3 Hepatic encephalopathy stage III or IV

Precoma or coma in a patient with signs and symptoms of liver failure and no other explanation for precoma or coma.
Stage III = pre-coma; stage IV = coma.

8.4.4 Hepatorenal syndrome

Acute renal failure in patient with existing severe chronic liver disease.

8.4.5 Liver cirrhosis

Pathology report report documenting cirrhosis (Cirrhotic nodules and broad collagen bands corresponding to Metavir F4)
or
Fibro-scan assessment in stable condition (acute hepatitis excluded) highly suggestive of cirrhosis: liver stiffness >= 18 kPa

8.4.6 NASH (Non-alcoholic steatosis hepatis)

Definitive: Elevated liver enzymes plus histology of fatty liver disease in a patient without any other identifiable cause, i.e. exclusion of alcohol use, hepatitis virus infections and other known causes of liver diseases.
Presumptive: Elevated liver enzymes plus findings in ultrasonography or other imaging methods indicating fatty liver disease in a patient without any other identifiable cause, i.e. exclusion of alcohol use, hepatitis virus infections and other known causes of liver diseases.

8.4.7 Portal hypertension

Portal pressure gradient (the difference in pressure between the portal vein and the hepatic veins) of 5 mm Hg or greater.

8.5 Kidney-related events

8.5.1 Permanent dialysis

Indicate start date. Hemodialysis or peritoneal dialysis expected to last at least one month, documented in a clinical note.

8.6 Bone-related events

8.6.1 Avascular necrosis femoral head

Synonyms: Avascular necrosis of the femoral head, osteonecrosis of the femoral head, ischemic necrosis of the femoral head, bone necrosis of the femoral head, bone infarct of the femoral head, idiopathic bone necrosis of the femoral head, nontraumatic avascular necrosis of the femoral head, traumatic avascular necrosis of the femoral head, subchondral avascular necrosis.
Diagnosis: Confirmed by MRI or histology.

8.6.2 Avascular necrosis other bone

as above.

8.6.3 Diagnosis of osteoporosis

Osteoporosis: Bone mass that is 2.5 SD or more below the young adult mean bone mass.
Diagnosis: confirmation by DEXA scan or by rheumatologist based on imaging techniques in a patient with or without fracture.

8.6.4 Fracture with adequate trauma

Fracture is plausible.

8.6.5 Fracture without adequate trauma

Fracture is not plausible based on patients history.

8.7 Bacterial pneumonia

Definitive: Signs and symptoms suggestive of bacterial pneumonia plus documented abnormality in chest x-ray or CT scan of lung compatible with bacterial pneumonia plus identification of a bacterial pathogen by blood culture, bronchoalveolar lavage or detection of Legionella or pneumococcal antigen in urine.
Presumptive: Signs and symptoms suggestive of bacterial pneumonia plus documented abnormality in chest x-ray or CT scan of lung compatible with bacterial pneumonia.

8.8 Pancreatitis

Definitive: Signs and symptoms suggestive of pancreatitis plus elevated pancreas enzymes plus documented structure abnormality in CT scan or MRI or other imaging techniques; or confirmed by histology.
Presumptive: Signs and symptoms suggestive of pancreatitis plus elevated pancreas enzymes without other explanation.

9. Other diagnoses

Any diagnosis that the treating physician would like to have documented has to be entered in the DISEASE form (database code ALI and AL2, AL3).

10. Familiy history and cardiovascular risks at baseline

At baseline, i.e. at enrollment into the SHCS, the following variables will be collected:

10.1 Family history of myocardial infarction and stroke

Myocardial infarction or stroke before age of 50 in any first degree relatives (genetic mother, father, brothers and sisters).

10.2 Family history of diabetes mellitus

Any diabetes mellitus in any first degree relatives (genetic mother, father, brothers and sisters).

10.3 Hypertension

Blood pressure > 160/95 mm Hg, at least three measures on two different days, patient being in sitting position for at least three minutes or on anti-hypertensive treatment

10.4 Smoking: Packyears

A measure of lifelong consumption of cigarettes: smoking during one year 20 cigarettes per day = 1 'packyear. Smoking during one year 10 cigarettes per day = ½ 'packyear.

11. Anthropometry and Lipodystrophy

11.1 Anthropometry

The circumferences should preferably be measured on standing subjects while they are semi-clothed, i.e. waist uncovered with the subjects wearing underclothes only. If this is not possible to follow, the alternative is to measure the circumference on subjects without heavy outer garments with all tight clothing, including the belt, loosened and with the pockets emptie.
Waist circumference: Record the measurement of the circumference at a level midway between the lower rib margin and iliac crest in cms to the nearest centimeter.
Hip circumference: Hip: Record measurement of maximum circumference over the buttocks in cms to the nearest centimeter.

11.2 Lipodystrophy

Fat-Wasting: Fat loss in any of the following regions: face, arms, legs, buttocks, breasts, neck. Presence of at least one patient-reported physical change confirmed on physical examination, irrespective of antiretroviral therapy or it's composition.
Fat-Accumulation: : Fat accumulation in any of the following regions: face, arms, legs, buttocks, abdomen, breasts, neck (including «buffalo hump»). Presence of at least one patient-reported physical change confirmed on physical examination, irrespective of antiretroviral therapy or it's composition.