cardiovascular protection exerted by premarin

QUALITY OF LIFE - A FEW DEFINITIONS
“.….gap between expectations and achievement:
the smaller the gap, the higher the quality of life”
Calman
…..ability to function cognitively, physically,
socially and sexually, to perform usual daily
activities” Stewart & King
“…..overall satisfaction with life and sense of
personal well-being” Shumaker
QUALITA’ DI VITA
Salvaguardare la salute di un
individuo significa non solo
assicurare il suo benessere fisico
ma anche quello psicologico
Menopause: factors that can affect QoL
 vasomotor and sleep disturbances
 psychological and emotional stress
 genitourinary and sexual complaints
 changes in body image
 op: backache, fractures
 CVD: angina
 Alzheimer disease
QUALITA’ DI VITA
•Uno dei principali sforzi del ginecologo
dovrebbe essere quello di eliminare o
migliorare questi sintomi
• HRT può essere utilizzata per mantenere
l’efficienza fisica e psicologica quotidiana
della donna in menopausa
Women’s Health Questionnaire (WHQ) scores
according to menopausal status in 928 women
60
Anxiety/fears
Attractiveness
50
Depressed mood
40
Memory/concentration
30
Menstrual symptoms
Sexual behaviour
20
Sleep problems
10
Somatic symptoms
0
Premenopausal
Postmenopausal Postmenopausal
< 3 a.
> 3 a.
Vasomotor symptoms
CONSEGUENZE DELLA MENOPAUSA
A breve termine
A medio termine
Artralgie
Ansia
Sudorazioni
Vampate
Parestesie
Palpitazioni
Astenia
Depressione
Cefalea
Insonnia
Vertigini
Precordialgie
A lungo termine
Osteoporosi
Atrofia
genito-urinaria
Malattie
cardiovascolari
Peggioramento
funzioni cognitive
Danni cutanei e oculari
Progetto Menopausa Italia
sotto il patrocinio ed il coordinamento dell’AOGOI
Obiettivi
1) descrivere l’epidemiologia dell’approccio diagnostico-
terapeutico alla menopausa nei centri
specialistici in Italia
2) descrivere le conseguenze della menopausa stessa sulla
salute della donna.
Eleggibili per lo studio tutte le donne osservate per la
prima volta nel periodo di reclutamento presso i centri
collaboranti
Progetto Menopausa Italia
sotto il patrocinio ed il coordinamento dell’AOGOI
99.363 donne arruolate al 02/02/02
240 SPAC
185 U.O.
1 CED
PROGETTO DONNA QUALITÀ DI VITA
74 Centri Universitari e Ospedalieri sul territorio Nazionale
Presidente
Prof. A. R. Genazzani (Pisa)
Comitato Scientifico
Segreteria Scientifica
Prof. C. Campagnoli (Torino)
Prof .C. Nappi (Napoli)
Dr. M. Gambacciani (Pisa)
Prof. GiovanBatttista Serra(RM)
Comitato di Coordinamento
Prof. D. de Aloysio (Bologna)
Prof. C. Donati Sarti (Perugia)
Prof. S. Guaschino (Trieste)
Prof. A. Cianci (Catania)
Prof. F. Petraglia (Udine)
Prof. S.. Schonauer (Bari)
Prof. A. Volpe (Modena)
Prof . G. Palumbo (Catania)
Dr. A. Genazzani (Modena)
Prof. F. Bottiglioni (Bologna)
The WOMEN’S HEALTH QUESTIONNAIRE
WHQ (by Myra Hunter)
36 items combined into nine factors describing:
• somatic symptoms
• depressed mood
• cognitive difficulties
• anxiety/fear
• sexual function
• vasomotor symptoms
• sleeps problems
• menstrual symptoms
• attraction
All the questions are rated on four-point scale.
The MOS 36-Item Short-Form Health Survey
(SF- 36)
36 items combined into eight factors
• physical function
• physical role
• bodily pain
• general health
• vitality
• social function
• mental health
and two summarizing measures
• physical health
• mental health
The European Quality of Life Questionnaire EQ-5D
 Simple, generic measure
 Minimum number of questions
 It produces an overall single number, “an index”
of health status
Includes 5 dimensions:
• mobility
• personal care
• usual activities
• pain/discomfort
• anxiety/depression)
(with 5 questions, 3 levels of response for each dimension)
QUALITY OF LIFE EVALUATION IN
ITALIAN MENOPAUSAL WOMEN
•Multicentric study on the quality
of life (QoL ) in women aged
between 45 and 65 years,
attending menopause centres in
Italy.
•Each of 64 menopause centres
involved recruited up to 50
women, using random lists
stratified by HRT (yes – no).
QoL variables
• Age
• marital status
• employment, partners’ employment
• Employment was considered as a proxy for socio-economic status. To
this purpose, a socio-economic score (SES) was created, ranging from 1
to 6. The score was assigned as follows: unemployed, housewife=1;
retired=2; unskilled worker=3; skilled worker, artisan=4; technical,
clerical=5; professional, managerial=6. For married women, the
profession scoring higher between wife and husband was considered.
•
•
•
•
geographic area
menopause duration
presence of chronic diseases
presence of HRT
Percent distribution of the 2760 PMW according to
HRT ( on HRT, n=1342, 49%).
Women on HRT were significantly more likely to have a menopause
duration >3 years and significantly less likely to suffer from chronic
diseases.
Chronic disease
Duration of menopause
noHRT
100
80
40
HRT
HRT
0.00002
30
60
40
20
20
0
<3
>3
noHRT
10
YRS
0
0.0003
Percent distribution of the 2760 PMW according to
geographic area.
PMW attending menopause centres in northern Italy are older, with lower
education, lower socio-economic score and longer menopause duration.
nord
centre
sud
80
60
0.00007
30
40
20
20
10
0
0
<45
0.000001
40
45-54
<5
>54
6-8
9-13
>13
School education (years)
age (yrs)
0.00001
40
80
0.00006
60
30
40
20
20
10
0
0
1
2
3
4
5
Socio-economic score
6
<3
>3
YSM (years)
QUALITY OF LIFE EVALUATION IN
ITALIAN MENOPAUSAL WOMEN
1. Correlates of QoL were first investigated with a series of
bivariate analyses
2. To adjust for the possible confounding effects, multiple logistic
regression analyses were applied to evaluate the independent
role of variables investigated in predicting QoL
Results of the stepwise logistic regression analyses
with SF-36 scores as dependent variables.
• school education (the higher the education, the better the QoL),
• socio-economic score (the higher the SES, the better the QoL),
• geographic area (women in southern Italy showing worse QoL),
• presence of chronic conditions (associated with poorer QoL)
• marital status and menopause duration are not
related with any of the SF-36 areas
Independent predictors of SF-36 domains
HRT associated with better QoL in all of the areas investigated
PCS
*
*
MCS
Vitality
Social function
HRT No
HRT Sì
*
*
*
Role physical
Role emotional
Physical activity
*
*
*
*
Mental health
General health
Bodily pain
0
20
40
*
*p< 0.05
60
80
100
Stepwise logistic regression analyses with
SF-36 scores as dependent variables.
the use of HRT represents an independent predictor
for limitations due to emotional problems
Dolore
corp.
Salute
generale
Salute
mental
e
Attività
fisica
Role
physica
l
Social
function
Vitality
MCS
PCS
NS
NS
NS
NS
NS
0.005
HRT
Yes
No
Role
emotional
NS
NS
NS
NS
1.0
1.3
WHQ scores according to HRT use
HRT Sì
HRT No
*
Vasomotor symptoms
Somatic symptoms
*
Sleep problems
*
Sexual behaviour
Menstrual symptoms
*
Attractiveness
Anxiety/fears
0
20
• low school
education
*
•low SES
Memory/concentration
Depressed mood
A high score (lower
QoL) is associated
with:
•living in Southern
Italy
*
• presence of
chronic diseases
*
40
60
Results of the stepwise logistic regression analyses with
WHQ scores as dependent variables according to HRT
Anxiety/ fears
Attractive
ness
Depression
Memory/
concentr.
Menstrual
symptoms
Odds
Ratio
HRT
Sexual
problems
Somatic
sympt.
Odds
Ratio
NS
NS
NS
NS
No
1.0
1.5
p
.0001
.003
Vasomotor
sympt.
Odds
Ratio
NS
1.0
1.4
Yes
Sleep
problems
NS
1.0
2.6
.000
Untreated women showed a 40% increased risk of reporting
anxiety/fears, a 50% increased risk of sexual problems and a
more than two-fold increased risk of vasomotor symptoms
EQ-5D: Percentages of respondents referring absence of problems
Anxiety/depression
*
Pain/discomfort
HRT No
HRT Sì
*
Usual activity
*
Self-care
Mobility
* p< 0.05
0
20
40
60
80
100
EQ-5D Results of the stepwise logistic regression analyses
Mobility Self-care
Usual
activities
Pain/discomfort
0.02
0.03
HRT
No
1.0
1.0
HRT
Yes
1.4
1.2
p
NS
NS
Anxiety/
Thermometer
depression
NS
NS
The presence of chronic conditions and the geographic area
represent the most important predictors.
After adjusting for the other variables investigated, women
not treated with HRT show an increased risk of reporting
problems in the areas of usual activities and pain/discomfort
Progetto Menopausa Italia
Lombardia
in
Coordinatore: Massimo Luer
Situazione delle 18 SPAC della Lombardia al
24/02/2000
1301
1302
1303
1304
1305
1306
1307
1308
1309
1310
1311
1312
1313
1314
1315
1316
1318
1319
Ospedale S. Anna Divisione O. G.
Istituti Ospedalieri Carlo Poma Divisone O. G.
Clinica Ostetrico Ginecologica Spedali Civili. Ente Osp. Reg.
Ospedale S. Giuseppe Divisione O. G.
Ospedale Maggiore Divisione O. G.
Ospedale di Treviglio Divisione O. G.
Osp. Fornaroli
Istituto Nazionale Tumori
Ospedale Civile
Ospedale Niguarda Ca' Granda Divisione O. G.
Osp. Morelli Divisione O. G.
Ospedale Vimercate Divisione O. G.
Ospedale di Saronno Divisione O. G.
Ospedale di Melegnano Divisione O. G.
Ospedale di Lecco Divisone O. G.
Ospedale Sesto S. Giovanni Divisione O.G.
Casa di Cura S. Anna Divisione O.G.
Clinica S. Carlo Divisione O.G.
Como
Mantova
Brescia
Milano
Lodi
Treviglio (BG)
Magenta (MI)
Milano
Sondrio
Milano
Sondalo (SO)
Vimercate (MI)
Saronno (VA)
Melegnano (MI)
Lecco
Sesto S. Giovanni (MI)
Brescia
Paderno Dugnano (MI)
10
136
1045
691
886
234
276
41
292
104
249
464
344
380
892
332
71
181
9
59
915
442
723
195
240
40
241
94
190
251
278
236
849
262
70
170
Età: media e deviazione standard
Media: 54,31
Deviazione standard: 7,72
Numero soggetti: 5820
Età Menopausa spontanea
Media: 49,15
Deviazione standard: 4,30
Numero soggetti: 3247
Età media d’insorgenza della menopausa in Europa
Nazione
Età media
Inghilterra
50,8
Cecoslovacchia
51,2
Svezia
50,4
Scozia
50,1
Germania Est
51,1
Olanda
51,5
Italia
50,8
DETERMINANTI DELL’ETA’ DELLA
MENOPAUSA
• FUMO
–non fumatrici
–< 10
–10 - 20
–> 20
50,8 anni
50,7 anni
50,5 anni
50,0 anni
• ETA’ AL MENARCA
–<11
–12-13
– 14
50,4 anni
50,7 anni
51,2 anni
FREQUENZA ALL’AMBULATORIO
CONTROLLI
SOLO 1° VISITA
29%
71%
FREQUENZA ALL’AMBULATORIO
7%
NESSUNA TERAPIA
TERAPIA IN CORSO
TERAPIA PREGRESSA
39%
54%
SITUAZIONE NELLE DONNE CHE HANNO
EFFETTUATO SOLO 1° VISITA
VERALIPRIDE
GIA' IN CORSO
BIFOSFONATI ECC
PRESCRITTA
ESTROGENI TOPICI
EP COMBINATI
ESTROGENI TRANSD.
0
5
10
15
20
25
30
RELAZIONE FRA USO DI HRT PRIMA
DELLA VISITA E FATTORI SELEZIONATI
Odds Ratio (IC 95%)
• ISTRUZIONE
– Nessuna/elementare
– Media
– Superiore/università
1+
1,33 (1,22 - 1,46)
1,39 (1,27 - 1,53)
• IMC (kg/m2)
– <23,8
– 23,8 - 27,2
–  27,2
1+
0,76 (0,70 - 0,83)
0,60 (0,55 - 0,65)
RELAZIONE FRA USO DI HRT PRESCRITTO
ALLA VISITA E FATTORI SELEZIONATI
Odds Ratio (IC 95%)
• OSTEOPOROSI
– No
– Sì
1+
1,42 (1,26 -1,61)
• CVD
– No
– Sì
1+
1,02 (0,95 - 1,10)
SOSPENSIONE TERAPIA NELLE DONNE CHE
HANNO EFFETTUATO PIU’ CONTROLLI
TERAPIA
CONTINUATA
8%
TERAPIA SOSPESA
92%
MOTIVI DI SOSPENSIONE DELLA TERAPIA
20
18
16
14
MASTODINIA
RITENZIONE IDRICA
DIFFIDENZA-PAURA
PAURA CA
FLUSSO ANOMALO
ALLERGIA GENERALIZZATA
IRRITAZIONE LOCALE
12
10
8
6
4
2
0
ESTROGENI TRANSDERMICI (82%)
IDENTIKIT DELLE UTILIZZATRICI DI HRT
• reddito familiare e livelli di scolarità superiore
• più magre, praticano più esercizio fisico, hanno un assetto
lipidico più favorevole
• fumano di più e assumono più alcoolici
• sono più spesso isterectomizzate
• lamentano più spesso una sintomatologia climaterica (specie
artralgie)
CONCLUSIONI
“Perceptions of well-being in healthy, post-
menopausal women depend less upon biology
than on socio-economic circumstances,
individual experiences, resources and cultural
morals”
Hunt SM. Quality of Life Res 2000;9:709-719
Cross-sectional Evaluation of QoL,
Menopause and HRT
• different factors play an important role
– low education is associated with a higher risk of
reporting somatic and vasomotor symptoms,
– low Social Economic Scores exerts a negative effect
on attractiveness, depression and sleep problems
• HRT is a factor that can modify at least some aspects of
QoL in symptomatic PMW
CONCLUSIONI
HRT users
• have a shorter duration of menopause
• have less chronic diseases
• tend to be slightly more educated and to belong to
higher socio-economic classes, but these differences
were marginal
CONCLUSIONI
• At univariate analyses, HRT users showed a significantly better QoL in
all the areas investigated by the SF-36, in three of the six items of the
EQ-5D and in all the symptoms scores of the WHQ, with the only
exceptions of menstrual symptoms and memory/concentration.
• After adjusting the analyses for a large array of different socioeconomic and clinical variables, several associations between HRT use
and QoL became not significant, suggesting that they were mediated
by the other factors considered in this study.
• Nevertheless, HRT users showed a lower probability of reporting role
limitations due to emotional problems (SF-36) and anxiety/fears
(WHQ).
• HRT was also associated with a lower probability of reporting
problems in the usual activities and pain/discomfort items of the EQ5D
CONCLUSIONI
• When looking at menopause symptoms, HRT users
showed highly significant better outcomes in vasomotor
symptoms and sexual problems (particularly vaginal
dryness).
• HRT can be of benefit for many of the postmenopausal
mood changes, pain perception and social functioning,
sexual problems and vasomotor symptoms
• untreated women have a 40-50% increase in the risk of
suffering from anxiety and sexual problems, with an
almost 3- fold increase in the incidence of hot flushes
and sweats
Lombardia Terapie e Peso
1600
1400
1200
1000
800
600
400
200
0
ND
<50
51<>60
61<>70
71<>80
Fascie di Peso
81<>90
>90
Progetto Menopausa Italia
Statistiche per la regione Lombardia
Situazione al 24/02/2000
Situazione SPAC Lombardia al 24/02/2000
Spac
1300
1301
1302
1303
1304
1305
1306
1307
1308
1309
1310
1311
1312
1313
1314
1315
1316
1318
1319
Struttura
Ospedale S. Carlo Borromeo Divisione O. G.
Ospedale S. Anna Divisione O. G.
Istituti Ospedalieri Carlo Poma Divisone O. G.
Clinica Ostetrico Ginecologica Spedali Civili. Ente Osp. Reg.
Ospedale S. Giuseppe Divisione O. G.
Ospedale Maggiore Divisione O. G.
Ospedale di Treviglio Divisione O. G.
Osp. Fornaroli
Istituto Nazionale Tumori
Ospedale Civile
Ospedale Niguarda Ca' Granda Divisione O. G.
Osp. Morelli Divisione O. G.
Ospedale Vimercate Divisione O. G.
Ospedale di Saronno Divisione O. G.
Ospedale di Melegnano Divisione O. G.
Ospedale di Lecco Divisone O. G.
Ospedale Sesto S. Giovanni Divisione O.G.
Casa di Cura S. Anna Divisione O.G.
Clinica S. Carlo Divisione O.G.
Città
Milano
Como
Mantova
Brescia
Milano
Lodi
Treviglio (BG)
Magenta (MI)
Milano
Sondrio
Milano
Sondalo (SO)
Vimercate (MI)
Saronno (VA)
Melegnano (MI)
Lecco
Sesto S. Giovanni (MI)
Brescia
Paderno Dugnano (MI)
Totale Pazienti
Cartelle Reclutate
1156
10
136
1045
691
886
234
276
41
292
104
249
464
344
380
892
332
71
181
708
9
59
915
442
723
195
240
40
241
94
190
251
278
236
849
262
70
170
4500
4226
4000
3532
3500
Estrogenica Transdermica
Estrogenica per OS
3000
Estrogenica topica
2500
Progestinica per OS
Estroprogestinica transdermica
2000
Associazioni estroprogestinica per OS
Associazioni estrogeni-androgeni
1500
Antiestrogeni
1228
Bifosfonati e altri
1000
Veralipride
Calcio
499
500
341
303
168
17
0
31
4
67
HRT AND QoL
•Women on HRT were significantly more likely to have a menopause
duration >3 years and significantly less likely to suffer from chronic
diseases.
HRT
HRT free
Duration of
menopause
< 3 years
627 (55%) 782 (64%)
> 3 years
510 (45%) 444 (36%)
Chronic
diseases
306 (23%) 409 (29%)
0.00002
0.0003
“Healthy user
effect” should be
considered when
we evaluate the HRT
effects in Italy
Progetto Menopausa Italia
sotto il patrocinio ed il coordinamento dell’AOGOI
Obiettivo
migliorare la qualità di assistenza alle donne in
menopausa favorendo la diffusione culturale tra
medici, istituzione e diverse componenti del tessuto
sociale, organizzando relazioni e programmi
interdisciplinari. Si propone inoltre di istituire un
laboratorio di epidemiologia al fine di valutare
l'adeguatezza e la compliance delle strategie
mediche, promuovere, partecipare e monitorare
trials sperimentali
VALUTAZIONE DELLA QUALITA’ DI VITA
NELLE DONNE ITALIANE IN MENOPAUSA
Questionario WHQ
(Women’s Health Questionnaire)
Questionario sviluppato in Inghilterra per valutare
un ampio spettro di sintomi fisici e della sfera
emotiva nelle donne di mezza età, con particolare
attenzione alle modificazioni nello stato di salute e
di benessere, legate alla menopausa.
Il questionario è costituito di 36 domande con
risposte su una scala a 4 punti.
Le 36 domande si combinano in 9 fattori.
VALUTAZIONE DELLA QUALITA’ DI VITA
NELLE DONNE ITALIANE IN MENOPAUSA
SF36 Health Survey Instrument
Strumento generico più utilizzato in diversi paesi
per la valutazione della QdV
Contiene 36 items che concorrono a formare 8 scale
(physical function, role physical, bodily pain,
general health, vitality, social function, role
emotional, mental health) e 2 misure riassuntive
(stato di salute fisico e mentale)
PROGETTO DONNA QUALITÀ DI VITA
Confronto fra popolazione Italiana e Inglese*
Età (media  DS)
Punteggi scale WHQ:
Depressed mood
Somatic Symptoms
Vasomotor symptoms
Anxiety/fears
Sexual behaviour
Sleep problems
Menstrual symptoms
Memory/concentration
Attractiveness
Campione UK
(n=682)
Campione Italia
(n=416)
52.3  4.9
53.4  4.9
0.220.23
0.390.25
0.430.44
0.350.28
0.320.32
0.450.36
0.380.29
0.470.36
0.380.29
0.270.23
0.460.24
0.480.44
0.400.31
0.380.34
0.500.36
0.370.30
0.530.37
0.370.40
* M. Hunter. Psychology and Health 1992; 7: 45-54
Women’s Health Questionnaire (WHQ) scores according to menopausal status in 928 women
Premenopausal
Postmenopausal,
<3 yrs
Postmenopausal,
>3 yrs
WHQ scales
Mean+SD
Mean+SD
Mean+SD
p*
Anxiety/fears
0.35+0.31
0.44+0.31
0.35+0.32
0.001
Attractiveness
0.31+0.38
0.42+0.41
0.34+0.37
0.003
Depressed mood
0.25+0.23
0.29+0.23
0.24+0.23
0.02
Memory/concentration
0.42+0.37
0.54+0.37
0.48+0.36
0.0002
Menstrual symptoms
0.41+0.30
0.39+0.31
0.11+0.13
0.01
Sexual behaviour
0.25+0.30
0.37+0.33
0.41+0.37
0.0001
Sleep problems
0.47+0.37
0.54+0.37
0.47+0.39
n.s.
Somatic symptoms
0.43+0.25
0.48+0.24
0.41+0.23
0.008
Vasomotor symptoms
0.33+0.40
0.52+0.44
0.40+0.42
0.0001
* Kruskall-Wallis one-way ANOVA
PROGETTO DONNA QUALITÀ DI VITA
Valori SF-36 nelle due popolazioni
Aree SF-36
Attività fisica
Ruolo e salute fisica
Ruolo emotivo
Vitalità
Salute mentale
Salute in generale
Dolore fisico
Attività sociali
*Mann-Whitney U-test
Popolazione Centri per la
generale
menopausa
(504 donne)
(424 donne)
87.9 
77.9 
74.5 
57.7 
64.4 
65.5 
68.5 
72.2 
15.7
32.1
35.0
18.2
19.8
17.4
23.4
22.3
83.6 
70.0 
66.6 
57.0 
63.1 
64.8 
67.8 
74.9 
17.1
35.1
38.0
18.2
19.3
17.8
25.0
22.1
p*
n.s.
n.s.
0.01
n.s.
n.s.
n.s.
n.s.
n.s.
“Progetto Donna Qualità di Vita”
Prima Fase
Risultati
Lo studio ha dimostrato che :
– la versione Italiana del WHQ è valida e riproducibile
–
non esistono differenze sostanziali in termini di
percezione della qualità della vita tra la popolazione
italiana e popolazioni dei Centri della Menopausa
Independent predictors of SF-36 domains
HRT associated with better QoL in all of the areas
investigated, including also the two summary measures
(physical and mental component scores).
Bodily
pain
General
health
Mental
health
Physical
activity
Role
emotio
Role
phys
Social
Vitality
function
HRT
p=0.005
p=0.001
p=0.03
p=0.003
p=0.003
p=0.009
p=0.02
Yes
No
67±24
64±23
64±18
61±18
64±19
62±20
85±17
82±19
71±37
66±39
74±35
69±37
74±21
72±22
MCS
PCS
p=0.03
p=0.03
p=0.008
59±19
57±19
45±11
44±11
49±8
48±8
EQ-5D : Percentages of respondents referring absence of problems and
mean values of the thermometer, according to HRT use
Mobility
Self-care
Usual
activity
Pain/discomfort
Anxiety/
depression
Thermometer
HRT
NS
NS
p=0.01
p=0.02
p=0.04
NS
No
85%
96%
82%
34%
28%
72.7±16
Yes
88%
97%
86%
40%
33%
73.9±15
Women on HRT reported less often to have problems in the areas
of usual activities, pain/discomfort and anxiety/depression
WHQ scores according to HRT use
A high score (lower QoL) is associated with low school
education, low SES, living in Southern Italy and presence
of chronic diseases
HRT
Yes
No
Anxiety/
fears
Attractiv
eness
Depressi
on
Memory/
concent
r.
Menstru
al
sympto
ms
Sexual
problem
s
Sleep
problem
s
Somati
c
sympt.
Vasomoto
r sympt.
p=0.0008
p=0.02
p=0.03
NS
NS
p=0.006
p=0.0004
p=0.006
p<0.0001
0.36±0.3
0.41±0.3
0.33±0.4
0.37±0.4
0.26±0.2
0.48±0.4
0.50±0.4
0.23±0.3
0.24±0.3
0.34±0.3
0.38±0.3
0.47±0.4
0.53±0.4
0.44±.3
0.47±.4
0.28±0.4
0.48±0.4
0.29±0.2