ml/min/month

L’importanza di far sapere
cosa si fa e per chi. Informare
sui risultati
Paolo Cravedi
Istituto di Ricerche Farmacologiche
Mario Negri, Bergamo
Seriate, 16 Dicembre 2010
1
Chi stabilisce in medicina cosa è efficace
e cosa no?
Una volta c’era qualche conoscenza sulle
cause delle malattie (non molte, fino a 60
anni fa) e soprattutto “l’esperienza” del
medico
Esperienza era aver visto altri casi simili e
cercare di ricordarsi chi, in seguito a
quale cura, stava meglio o era guarito e
chi no
I nuovi ammalati si curavano con
quello che si pensava avesse fatto
bene agli altri
Molti medici le loro esperienze le
scrivevano su libri o riviste
Altri ne parlavano con altri medici, si
creava una tradizione ma questo
metodo era molto pericoloso
A metà del ‘700 James Lind dottore di Edimburgo a bordo
di una delle navi della regina era in un bel guaio, i marinai
sanguinavano dalle gengive e
perdevano i denti: scorbuto
Image from A History of Medicine, by Parke, Davis & Co, 1960. Artist: Robert A. Thom
Lind divise 12 marinai in sei
gruppi di due
Ciascuno dei due della
coppia avrebbe avuto un
trattamento
diverso
da
quello delle altre coppie
Solo i due marinai che
avevano avuto succo di
agrumi (di due arance e
un limone al giorno)
guarirono, gli altri no
Lind lo scrisse
Fu probabilmente il primo studio clinico
controllato
SE SI VUOLE SPERIMENTARE SULL’UOMO UN
FARMACO SERVONO (IN ITALIA E IN TUTTO IL
MONDO)
1 - Dati di laboratorio che suggeriscano
meccanismo d’azione plausibile
un
2 - Dati sull’animale che indichino che funziona
3 - Studi sul volontario sano che dimostrino che non fa
male
PLACEBO
Placebo e’ una qualsiasi sostanza innocua o
un qualsiasi intervento non farmacologico privi
di efficacia terapeutica.
E’ deliberatamente somministrato alla persona
che acconsente di assumerlo come alternativa
a un trattamento attivo di cui si voglia
sperimentare l’efficacia o la sicurezza.
L’uso del placebo quindi e’ legittimo solo a scopo
sperimentale e solo in presenza del consenso informato del
paziente e, secondo la Dichiarazione di Helsinki, solo se non
vi siano trattamenti di provata efficacia per la situazione
clinica soggetta a sperimentazione.
Somministrare un nuovo farmaco potenzialmente efficace al
di fuori di un contesto sperimentale significherebbe esporre
il paziente al rischio di una sua tossicita’ sconosciuta;
negarglielo a priori significherebbe privarlo della possibilita’
di goderne il possibile effetto benefico.
L’unica soluzione eticamente e
scientificamente
valida
e’
la
sperimentazione:
il
caso
(la
randomizzazione)
distribuira’
trattamento potenzialmente efficace o
placebo a una popolazione di pazienti
e il confronto dell’esito clinico nei due
gruppi di trattamento consentira’ di
concludere se il farmaco sperimentale
e’ superiore al placebo.
IMPACT OF SEVERITY AND DURATION OF ANEMIA ON
MORTALITY
IN
DIALYSIS:
RESULTS
FROM
OBSERVATIONAL STUDIES
Analysis on 2,790 dialysis patients
(Follow-up: 13 months)
A retrospective study on 41,919 dialysis
patients (follow-up: 2 years)
Hemoglobin level
(g/dL)
Percent of time
Hb < 11.0 g/dL
Mortality HR
(95 % CI)
<9
81-100
9-10
61- 80
10-11
41- 60
11-12
21- 40
12-13
1- 20
>13
Mortality HR
(95 % CI)
0
0.5
1.0
1.5
Robinson et al., Kidney Int, 2005
0.5
1.0
1.5
2.0
Ofsthun et al., Neph Dial Transpl, 2005
IN DIALYSIS PATIENTS, CORRECTION OF
ANEMIA DID NOT REDUCE MORTALITY IN
A RCT
Death or MI (%)
60
45
30
15
N = 615
N = 618
Placebo
EPO
0
Follow up: 30 months
Besarab et al., N Engl J Med, 1998
EFFECT OF ANEMIA IN THE RAT MODEL
OF RENAL MASS ABLATION
Glomerulosclerosis
P<0.05
60
Percent
50
40
30
20
10
Vehicle
EPO
Lafferty HM, Am J Kidney Dis, 1991
Randomized controlled trials:
are they always really worth?
The Remission Clinic
REIN-1/REIN-2
Cumulative incidence of
patients with ESKD (%)
60
50
40
30
P < 0.0015
20
10
Remission Clinic
0
0
6
12 18 24 30 36 42 48 54 60 66 72 78
months
Reviewer ## (from New England Journal of Medicine)
“Though the results of this study
are of interests, it can be argued
that findings essentially provide
very good rational for a randomized
clinical
trial
comparing
this
Remission Clinic approach versus
conventional therapy”
The Remission Clinic
REIN-1/REIN-2
Cumulative incidence of
patients with ESKD (%)
60
50
40
30
P < 0.0015
20
10
Remission Clinic
0
0
6
12 18 24 30 36 42 48 54 60 66 72 78
months
Ruggenenti et al., J Am Soc Nephrol, 2008
Design:
Systematic review of randomized controlled trials
Data sources:
Medline, Web of Science, Embase, and the Cochrane
Library databases
Study selection:
Studies showing the effects of using a parachute during free fall
Main outcome measure:
Death or major trauma defined as an injury severity score > 15
No randomized controlled
trials of parachute use
have been undertaken
The basis for parachute use is
purely observational
The parachute industry has
earned billions of dollars
depending on belief in the
efficacy of their product
Many current treatments - e.g. steroids in many
autoimmune disases - are not based on results
from RCT. Their efficacy is self evident and it
would sound unethical to test them against
placebo.
On the other hand, we are watching the growth
of trials with ‘new’ molecules whose results do
not to provide any major advantage (at least not
to patients) over current medical practive.
NON INFERIORITY TRIALS
The new products offer little innovation. Some
analyses indicate that only 10-20% of the products
reaching the market offer substantial advantages
over existing ones
Use of equivalence or non-inferiority trials rather
than superiority designs implies the intention of not
trying to prove any additional value of new drugs
Non-inferiority allows new products to compete
with older ones on the basis of small differences
made to seem to benefit patients
Garattini S, BJCP, 2004
UNRELIABILITY OF EQUIVALENCE TRIALS,
WICH CAN EVEN DISPROVE CONSOLIDATED
CLINICAL EVIDENCE
Death (%)
20
P<0.0001
15
Difference assumed
by noninferiority trial
COMPASS
10
5
0
SK
Placebo
Effect of streptokinase on mortality at 21 days after the onset of
symptoms in patients with miocardial infarction
GISSI Group, Lancet, 1986
Assuming as equivalent a treatment that can
result in 50% excess mortality is open to
criticism from both the ethical and the
methodological
point
of
view.
Equivalence trials should not be accepted as
a basis for marketing authorization by the
regulatory authorities.
A more convincing approach might
be to limit non-inferiority trials for
the sake of improved safety
ADVERSE DRUG REACTIONS ARE THE FOURTH
LEADING CAUSE OF DEATH IN U.S.A.
Cause of death (%)
60
cardiovascular
diseases
50
Drug use *
(5.5%)
40
30
cancer
20
10
others
medical
car
errors
accident
suicide
smoking
alcool
0
* Illegal substances were excluded
Over 2 millions hospitalized patients experienced adverse drug reactions.
Lazarou, JAMA 1998
SERIOUS ADVERSE DRUG REACTIONS (ADRs)
REPORTED TO THE FDA, 1998 – 2005
15107
(+170%)
16000
80000
89842
(+150%)
12000
60000
Death
Seriuous ADRs
100000
8000
5519
40000
34966
4000
20000
0
0
1998
1999
2000
2001
2002
2003
2004
2005
Year
Moore, Arch Intern Med 2007
Even to test superior safety profile of a new
drug compared to older ones, a superiority
trial would be a preferable way to compare
effectiveness of two treatments in terms of
survival without adverse events.
The Story of Chronic Kidney
Disease
PROGRESSION OF RENAL FAILURE IN 9 DIABETICS
1/Cr x 10 3 (µmol/l)
80
GFR
60
ml/min/month
0.2
40
20
GFR
GFR
ml/min/month
ml/min/month
5
2
0
0
10
20
30
40
50
Time (months)
Modified from Jones et al., Lancet, 1979
Glomerular hypertension
Disease progression
THE NATURAL HISTORY OF DIABETIC NEPHROPATHY
Albuminuria (mg/24h)
3000
21-50%
300
30
3 - 9 years
3
Normoalbuminuria
Micro
UAE µg/min< 20
0
13
Macro
20 - 200
18
Duration of diabetes (years)
ESRD
> 200
25
GFR IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES
AND MICRO OR MACROALBUMINURIA
GFR (ml/min/year)
0
-10
-20
-30
-40
Normo*
Micro**
Macro***
(n = 101)
(n = 114)
(n = 354)
*
BENEDICT, Phase A
** BENEDICT, Phase B
*** Parving et al., Pooled analysis, Curr Opin, 2002
PATHOPHYSIOLOGY OF PROGRESSIVE NEPHROPATHIES
Glomerular-capillary
hypertension
Increased glomerular
permeability to macromolecules
Increased filtration of plasma proteins
Excessive tubular reabsorption
Nuclear signals for NF-kB-dependent and
independent vasoactive and inflammatory genes.
Corresponding protein products then released
into interstitium
Tubular cell apoptosis
Glomerular-tubule disconnection
GFR loss
Remuzzi and Bertani, N Engl J Med, 1998
Podocyte loss
Proteinuria
PREDICTED  GFRs ACCORDING
MORNING URINE P/C RANGES
+ 0.4
TO
DIFFERENT
SPOT
+ 0.13±0.27
 GFR (ml/min/month)
0
- 0.4
- 0.31±0.19
- 0.8
-0.61±0.26
- 1.2
- 1.6
- 2.0
- 2.19±1.03
- 3.4
<1
1-2.5
2.5-4
>4
Base-line spot morning P/C ratio (g/g)
Remuzzi and Bertani, N Engl J Med, 1998
DIABETES
Experimental
Diabetic +
losartan
Remuzzi A. et al., J Am Soc Nephrol, 1993
*
700
600
(mg/24 hrs)
Urinary Protein Excretion
UNINEPHRECTOMIZED MWF/ZTM RATS - 1
500
400
300
200
100
0
**
Control
UNx + Lis
*
100
Percentage of glomeruli
affected by sclerosis
UNx
80
60
40
20
**
0
Control
UNx
UNx + Lis
* p < 0.05, **p < 0.01 vs control
Remuzzi A. et al., Kidney Int, 1995
UNINEPHRECTOMIZED MWF/ZTM RATS - 2
Control
UNx + Lis
100
Survival (%)
80
60
40
20
UNx
0
0
3
6
9
12
15
Time (months after UNx)
Remuzzi A. et al., Kidney Int, 1995
THE PREDICTIVE VALUE OF PROTEINURIA
- UKPDS 64
- 5,097 type 2 diabetics
- Follow-up: 10 years
(percent/year)
20
Mortality
15
10
5
0
Normo
Micro
Overt
nephropathy
Adler et al., Kidney Int, 2003
REIN CORE
Rate of GFR decline according to base-line proteinuria
- Interim analysis on 177 patients
GFR decline
Change in proteinuria
p=0.001
P < 0.002
40
1.0
p=0.001
0.67±0.08
(ml/min/month)
Rate of GFR decline
1.0
0.5
(ml/min/month)
20
%0
0.5
-20
-40
0.25±0.08
-60
0
Conventional Ramipril
0
STRATUM - 1
Conventional Ramipril
STRATUM - 2
U. Prot. 1-3 g/24 h U. Prot. ≥ 3 g/24 h
Kidney survival: Conventional 54 %
Ramipril 77 %
GISEN Group, Lancet, 1997
REIN CORE
% patients with doubling of baseline creatinine or ESRF
1.4
(ml/min/month)
Mean rate of GFR decline
1.6
Conventional
Ramipril
1.2
1.0
0.8
0.6
0.4
0.2
0
70
60
50
40
30
20
10
0
3 - 4.5 4.5 - 7
≥7
Baseline proteinuria (g/24 h)
3 - 4.5 4.5 - 7
≥7
Baseline proteinuria (g/24 h)
GISEN Group, Lancet, 1997
45
Ramipril
Ramipril
 GFR = -0.44 ± 0.54
(ml/min/month)
GFR
40
 GFR = - 0.10 ± 0.50
35
30  GFR = -0.81 ± 1.12
25
Conventional
CORE
 GFR = -0.14 ± 0.87
Ramipril
FOLLOW-UP
Ruggenenti et al., Lancet, 1998
CONTINUED RAMIPRIL
≥ 60 months
Cohorts
45
GFR (ml/min/month)
40
35
30
25
-.16 -.13 -.11
20
0
18
30
42
-.10
60 months
REGRESSION
10 patients with increasing GFR
Proteinuria
(pre vs post break point)
P = 0.01
60
55
GFR
-0.21 + 0.09
+0.49 + 0.19
(ml/min/month)
0
50
45
-20
40
%
GFR (ml/min/month)
65
35
-40
30
25
Break point
20
-30
-20
-10
0
10
-60
20
30
months
Ruggenenti et al., J Am Soc Nephrol, 1999
Treatment
GFR (ml/min/1.73 m2)
100
DM-2-nephropathy
Non-DM-nephropathies (remission - DETAIL)
(regression-REIN)
DM-nephropathy
(remission)
80
60
40
Non-DM-nephropathies
(remission - REIN)
20
SLE-chronic nephropathy
(remission)
0
-1
0
1
2
3
4
5
6
7
Years
Remuzzi, Benigni, Remuzzi, J Clin Invest, 2006
% of Capillary Tuft Volume
Affected by Sclerosis
100
75
MWF 50W
50
25
0
0
10
20
30
40
50
60
70
80
90
100
Reconstructed Glomeruli
A Remuzzi, et al., Kidney Int, 2006
% of Capillary Tuft Volume
Affected by Sclerosis
100
75
MWF 50W
MWF 60W
50
25
0
0
10
20
30
40
50
60
70
80
90
100
Reconstructed Glomeruli
A Remuzzi, et al., Kidney Int, 2006
% of Capillary Tuft Volume
Affected by Sclerosis
100
75
MWF 50W
MWF 60W
50
25
MWF + LIS 50-60W
0
0
10
20
30
40
50
60
70
80
90
100
Reconstructed Glomeruli
A Remuzzi, et al., Kidney Int, 2006
Sclerosis was effectively reabsorbed and a
consistent amount of glomerular tissue
regained normal structure
This suggests neoformation of glomerular
capillary segments
INSIGHT
INTO
ACE-INDUCED
REPAIR/ANGIOGENESIS
RENAL
Renal cells
Adult differentiated
Resident progenitor/stem
Extra renal cells
Endothelial progenitor and/or bone marrowderived stem
Migration of parietal cells from the Bowman’s capsule to capillary tuft
PARIETAL CELLS WITH PODOCYTE PHENOTYPE
Parietal podocytes (%)
12
*
10
8
6
4
2
0
MWF
40 W
MWF
60 W
MWF + Lis
60 W
These cells were identified by staining for PGP 9.5 (parietal epithelial cell
marker) and WT1 (podocyte marker)
Macconi et al., 2008
NON-DIABETIC CHRONIC NEPHROPATHIES
Ramipril
(n = 20)
GFR
3
70
2
60
ml/min
g/24 hours
Proteinuria
1
50
0
40
0
6
12
months
18
24
0
6
12
months
18
24
REIN-2 study
338 patients with non-diabetic chronic renal disease and proteinuria
> 1 gr/24 hour, Cr. Cl. < 70 ml/min
Ramipril +
Felodipine
40
Ramipril
35
30
25
15
10
5
(mmHg)
140
20
Follow-up SBP
Subjects with ESRD (%)
45
130
120
0
0
6
12
18
24
30
36
Follow-up (months)
p < 0.0019
42
R+F
R
48
54
Ruggenenti et al., Lancet, 2005
800
Treatment for 10 months (start treatment at 2 months)
600
(mg/day)
Urinary protein excretion
SEVERE PASSIVE HEYMANN NEPHRITIS (UNINEPHRECTOMY)
*
400
200
60
(%)
Glomerulosclerosis
0
80
40
*
*
20
0
Vehicle
Lisinopril
Lis + AII-RA
Control
Zoja et al., J Am Soc Nephrol, 2002
A CASE-CONTROL STUDY OF SINGLE OR DUAL RAS INHIBITION IN
PATIENTS WITH NON-DIABETIC CHRONIC NEPHROPATHIES
Ramipril
(n = 20)
Benazepril + Valsartan (n = 20)
GFR
3
70
2
60
* p < 0.01
1
ml/min
g/24 hours
Proteinuria
50
*
0
0
6
*
12
months
*
*
40
18
24
0
6
12
months
18
24
REMISSION CLINIC
Recommend DASH* Diet
Add low-dose ACEi or ARB
Up-titrate ACEi or ARB
K < 5.5 mEq/l
Add a diuretic
K > 5.5 mEq/l
Correct metabolic acidosis
Optimize metabolic control
Add and up-titrate AII RA or ACEi
Add low-dose Aldos-antagonist
Add and up titrate concomitant antihypertensive agents to achieve the
maximum tolerated blood pressure reduction (consider dCCBs as last choice)
Add a lipid lowering agent
Vitamin D ?
* Dietary Approaches to Stop Hypertension, with low potassium
Ruggenenti et al., Lancet, 2001
REMISSION CLINIC
Targets:
Blood pressure
Proteinuria
LDL
LDL + VLDL
HbA1c
< 120/80 mmHg
< 0.3 g/24 h
< 100 mg/dl
< 130 mg/dl
< 7.5 %
Ruggenenti et al., Lancet, 2001
The Remission Clinic
A matched-cohort study
- 56 reference patients:
CKD from REIN or REIN2
Proteinuria > 3 g/24 h
On Ramipril (5 mg/d) for > 6 months
- 56 patients:
CKD
Proteinuria > 3 g/24 h
ACEi or ARB therapy for > 6 months
- Matching:
1:1
Age
Gender
Creatinine clearance (+ 5 ml/min)
Proteinuria (+ 1 g/24 h)
- Outcomes:
ESRD, GFR (CrCl), 24 h proteinuria
The Remission Clinic
Cumulative incidence of
patients with ESRD (%)
60
Ramipril (reference-patients)
50
40
30
P < 0.0015
20
10
Remission Clinic (patients)
0
0
6
12 18 24 30 36 42 48 54 60 66 72 78
months
Ruggenenti et al., J Am Soc Nephrol, 2008
80
Placebo (REIN1)
60
Cumulative incidence of
patients with ESRD (%)
Ramipril
(historical controls)*
(reference-patients)
50
40
30
20
Remission Clinic
10
(patients)
0
0
6
12
18
24
30
36 42
months
48
54
60
* Patients from REIN with CKD and proteinuria > 3 g /24 h
66
72
78
Non - Diabetics
Pre
 GFR (ml/min/months)
0
Post
Diabetics
Pre
Post
Post
0.20
0.40
0.60
0.80
p < 0.0001
Ruggenenti et al., J Am Soc Nephrol, 2008
EVIDENCE THAT ACE-I HAS A DIFFERENT EFFECT ON GLOMERULAR
INJURY ACCORDING TO THE DIFFERENT PHASE OF THE DISEASE AT
WHICH THE TREATMENT IS STARTED
Diabetes
300
*
160
120
ACEi
*
80
Diabetes +
ACEi
40
0
Proteinuria (mg/24h)
Proteinuria (mg/24h)
200
Diabetes
ACEi
200
Diabetes +
ACEi
100
0
0
20-24
24-28
Time (weeks)
28-32
0
31-33
35-37
39-41
Time (weeks)
Perico et al., J Am Soc Nephrol, 1994
BENEDICT
Normoalbuminuria
Micro
UAE µg/min < 20
0
Macro
20 - 200
13
Duration of diabetes (years)
18
ESRD
> 200
25
Age:
SBP:
DBP:
S. Creat:
BENEDICT Study
Screened patients: 6.500
Included: 1.200
> 40 yrs
> 130 mmHg
> 85 mmHg
< 1.5 mg/dl
Cumulative incidence of
microalbuminuria (%)
15
Placebo
(mmHg)
Follow-up MAP
120
80
60
10
(30 events)
100
P
T+V
5
Trandolapril plus
verapamil
(17 events)
0
0
6
12
18
24
30
36
42
48
Follow-up (months)
Ruggenenti et al., N Engl J Med, 2004
Cumulative incidence of
microalbuminuria (%)
15
120
(mmHg)
Follow-up MAP
BENEDICT Study
Placebo
100
(30 events)
80
60
10
P
T
5
Trandolapril
(18 events)
0
0
6
12
18
24
30
36
42
48
Follow-up (months)
Ruggenenti et al., N Engl J Med, 2004
BENEDICT
Follow-up blood pressure
25
Subjects with
microalbuminuria (%)
ACEi NO
Subjects with
microalbuminuria (%)
20
Follow up SBP
>139.16 mmHg
20
15
10
ACEi YES
5
HR: 0.36 (95%CI: 0.20-0.63), p=0.0004
15
0
0
1
2
3
4
5
6
years
10
5
Follow up SBP
<139.16 mmHg
0
0
1
2
3
4
5
6 years
HR: 1.57 (95%CI: 1.03-2.41), p=0.0378 Adjusted for ACEi therapy
Ruggenenti et al., J Am Soc Nephrol, 2006
Baseline BP did not predict the risk
of developing microalbuminuria
on follow-up
Lower incidence of microalbuminuria
observed with more effective BP
control, reflected a benefit of
treatment
DIABETICS WITH HYPERTENSION
25
should be treated to prevent
1
new case of microalbuminuria
over 3 to 4 years
HIGH NORMAL ALBUMINURIA IS THE STRONGEST
PREDICTOR OF MICROALBUMINURIA
Incidence of microalbuminuria
(%)
A post-hoc analysis of the BENEDICT study
30
p < 0.001
20
10
0
Low-normal
< 10
High-normal
> 10
Baseline UAE (µg/min)
Perna et al., Personal communication
DIABETICS WITH HYPERTENSION
AND HIGH-NORMAL ALBUMINURIA
3
should be treated to prevent
1
new case of microalbuminuria
over 3 to 4 years
The BENEDICT Network
1. Centro Dacco’ (Ranica)
4
2. Bergamo
3. Alzano Lombardo
7
1
4. Clusone
2
6
5. Romano di Lombardia
6. Ponte S. Pietro
7. Seriate
8. Treviglio
8
5
3
PROGRESSION OF RENAL FAILURE IN 9 DIABETICS
1/Cr x 10 3 (µmol/l)
80
GFR
60
ml/min/month
0.2
40
20
GFR
GFR
ml/min/month
ml/min/month
5
2
0
0
10
20
30
40
50
Time (months)
Modified from Jones et al., Lancet, 1979
Insulin resistance/endothelial dysfunction
Reduced
nephron
number ?
(ml/min/1.73m2)
Worsening metabolic syndrome
Increasing cardiovascular risk
ACEi
150
GFR
Unselective proteinuria
- Obesity
Albuminuria
- Hypertension
- Diabetes
?
100
Transient hyperglycemia,
hypertension
50
0
Normoalbuminuria
UAE µg/min < 20
0
Micro
Macro
20 - 200
> 200
10
15
Duration of diabetes (years)
ESRD
25
TYPE 2 DIABETIC ESRD INCIDENCE RATE
Changes from 1991 to 2000 (US)
200
%
100
75
50
25
0
20-39
40-49
50-59
60-74
> 75
Age
-25
Coresh et al., Nephrology Self-Assessment Program, 2005
Screened subjects (20,560)
Ulaanbatar, Mongolia
1167
China
Chisinau/Ialovani,
Dharan, Nepal
Moldova 1025
6885
QuickTi me™ e un
decomp resso re TIFF (Non co mpres so)
son o ne ces sari per vis uali zzare que st'imma gine .
Damanhour,
Egypt, 699
Kolkata,
India, 600
Beijing, 2310
Wanzai, 739
Fuxing, 763
Guilin, 4207
La Paz, Bolivia
2165
KDDC COORDINATING CENTER
Centers
SERVER
Unit conversion for
laboratory tests
(i.e: serum Creatinine
from µmol/l to mg/dl)
www.isn-online.org
FOLLOW-UP AT RENAL DISEASE PREVENTION
CLINIC (NEPAL)
Subjects (number)
13000
Follow-up: 3240 patients
12000
After 6 to 30 months:
8000
- BP control <140/90:
73%
- Fasting glucose <120 mg/dl:
63%
- Reduction or stable proteinuria:
51%
4100
4000
0
Screened
Positive*
* Hypertension, diabetes, proteinuria, CKD
Lifestyle modifications plus low costs drugs (antihypertensives, antiproteinurics
and/or oral antidiabetics)
1,000,000 deaths
A lot of people think that
scientists do not respect ethical
and human values and
consider science as something
in conflict with faith
L’Espresso, 1 ottobre 2009
Il prezzo della vita
di Daniela Minerva
Farmaci mirati: a volte efficaci, a volte no. Ma che possono allungare anche di
pochi mesi un'esistenza. Sono costosissimi.
E i medici si chiedono: vale la pena sperimentarli?
Journal of the National Cancer Institute, 2009
We must deal with the escalating price of cancer
therapy now
If we allow a survival advantage of 1.2 months to
be worth $ 80 000, and by extrapolation survival of
1 year to be valued at $ 800 000, we would need $
440 billion annually - an amount nearly 100 times
the budget of the National Cancer Institute - to
extend by 1 year the life of the 550 000 Americans
who die of cancer annually
And no one would be cured
The current situation cannot continue
We cannot ignore the cumulative costs of
the tests and treatments we recommend and
prescribe
As the agents of change, professional
societies, including their academic and
practicing oncologist members, must lead
the way
The time to start is now
We politicians - concluded Hillary Clinton - we
absolutely need you. What we also need are
partnerships between the government and
academic and research institutions. But you
scientists have to raise your voice and stand up
for science, you should participate in the debate
personally
‘Thanks for what you are doing’ she told the
transplant physicians before leaving ‘and for
everything you did in these 50 years for million of
people’
Immediately after Alonzo Mourning (famous
basketball player from Miami) came on stage
Black, about 7 feet tall, speaking like an old actor
who everytime when he jokes is waiting for the
reaction of the audience. Really funny, you can
listen for hours to him
Three years ago he received a kidney transplant
This year the Miami
Heat won the NBA
championship
and
they won for Alonzo
Mourning
Dr. Hardy said “I have done thousands of
these, and I can do it with my eyes closed”
My response to him “Well, make sure you at
least keep one eye open when you are doing
my surgery”
Alonzo Mourning, World Transplant Congress, 2006