Differences in the use of health resources by Spanish and immigrant HIV-infected patients.
ABSTRACT HIV-immigrant use of health services and related cost has hardly been analysed. We compared resource utilisation patterns and direct health care costs between Spanish and immigrant HIV-infected patients.
All HIV-infected adult patients treated during the years 2003-2005 (372 patients) in this hospital were included. We evaluated the number of out-patient, Emergency Room (ER) and Day-care Unit visits, and number and length of admissions. Direct costs were analysed. We compared all variables between immigrant and Spanish patients.
Immigrants represented 12% (n=43) of the cohort. There were no differences in the number of out-patient, ER, and day-care hospital visits per patient between both groups. The number of hospital admissions per patient for any cause was higher in immigrant than in Spanish patients, 1.3 (4.4) versus 0.9 (2.7), P=.034. A high proportion of visits, both for the immigrant (45.1%) and Spanish patients (43.0%), took place in services other than Infectious Diseases. Mean unitary cost per patient per admission, out-patient visits and ER visits were similar between groups. Pharmacy costs per year was higher in Spanish patients than in immigrants (7351.8 versus 7153.9 euros [year 2005], P=.012). There were no differences in the total cost per patient per year between both groups. The global distribution of cost was very similar between both groups; almost 75% of the total cost was attributed to pharmacy in both groups.
There are no significant differences in health resource utilisation and associated costs between immigrant and Spanish HIV patients.
Article: The changing pattern of tuberculosis and HIV co-infection in immigrants and Spaniards in the last 20 years.[show abstract] [hide abstract]
ABSTRACT: To evaluate the impact of immigration on tuberculosis (TB)-HIV co-infection in Spain in a prospective cohort of HIV patients. Among 7761 HIV patients, we evaluated 1284 with at least one episode of TB between 1987 and 2006. Variables were compared between immigrants and Spaniards. Incidence of TB decreased from 20 to five cases per 100 patient-years in 2006 (P<0.01) and was always higher in immigrants than in Spaniards. The proportion of immigrants increased, reaching almost 50% of both new cases of HIV and TB-HIV co-infection in 2006. In 34.4% of patients, TB and HIV infection were diagnosed within the same year; simultaneous diagnosis was more frequent in immigrants (83.3%vs. 16.7%, P<0.001). Mortality was associated independently with age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05], TB diagnosis before 1996 (HR 2.6, 95% CI 1.8-3.6), use of highly active antiretroviral treatment (HR 0.494, 95% CI 0.37-0.66) and CD4 cell count at TB diagnosis (HR 0.996, 95% CI 0.995-0.997). Immigrants have a major impact on the incidence of TB in HIV patients, slowing down the decreasing trend in Spain. Simultaneous diagnosis of the co-infection in immigrants reveals a need to intensify HIV case finding in immigrants in Spain.HIV Medicine 05/2008; 9(4):227-33. · 3.01 Impact Factor
Article: Expenditures for the care of HIV-infected patients in the era of highly active antiretroviral therapy.[show abstract] [hide abstract]
ABSTRACT: The introduction of expensive but very effective antiviral medications has led to questions about the effects on the total use of resources for the care of patients with human immunodeficiency virus (HIV) infection. We examined expenditures for the care of HIV-infected patients since the introduction of highly active antiretroviral therapy. We interviewed a random sample of 2864 patients who were representative of all American adults receiving care for HIV infection in early 1996, and followed them for up to 36 months. We estimated the average expenditure per patient per month on the basis of self-reported information about care received. The mean expenditure was $1,792 per patient per month at base line, but it declined to $1,359 for survivors in 1997, since the increases in pharmaceutical expenditures were smaller than the reductions in hospital costs. Use of highly active antiretroviral therapy was independently associated with a reduction in expenditures. After adjustments for the interview date, clinical status, and deaths, the estimated annual expenditure declined from $20,300 per patient in 1996 to $18,300 in 1998. Expenditures among subgroups of patients varied by a factor of as much as three. Pharmaceutical costs were lowest and hospital costs highest among underserved groups, including blacks, women, and patients without private insurance. The total cost of care for adults with HIV infection has declined since the introduction of highly active antiretroviral therapy. Expenditures have increased for medications but have declined for other services. However, there are large variations in expenditures across subgroups of patients.New England Journal of Medicine 04/2001; 344(11):817-23. · 53.30 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: In the USA, Medicaid is the principal payer of the health care costs of patients with HIV infection. We wished to determine how the costs to Medicaid of patients in Maryland infected with HIV have changed in the setting of highly active antiretroviral treatment. Observational cohort study. Analysis of combined economic and clinical data of patients from the Johns Hopkins HIV Service, the provider of primary and sub-specialty care for a majority of HIV-infected patients in the Baltimore metropolitan region. All patients were enrolled in Medicaid and received care longitudinally in Maryland from 1 January 1995 through 31 December 1997. Monthly Medicaid payments were calculated for all inpatient and outpatient services by fiscal year, CD4 cell count, and use of protease inhibitors. For inpatients with a CD4 cell count < or = 50 x 10(6) cells/l, the total health care average monthly payments remained unchanged ($2629 in 1995, $2585 in 1997). Total mean monthly payments increased for those with a CD4 cell count > 50 x 10(6) cells/l (CD4 cell count 50-200 x 10(6) cells/l, $1172 in 1995 and $1615 in 1997, P < 0.05; CD4 cell count 201-500 x 10(6) cells/l, $1078 in 1995 and $1305 in 1997, P < 0.05). However, when data were stratified according to use of a protease inhibitor-containing regimen (used during approximately 50% of follow-up time in 1996-1997) it was found that hospital inpatient payments decreased significantly in all CD4 strata for patients on a protease inhibitor-containing regimen whereas pharmacy payments increased significantly. Inpatient payments associated with treating opportunistic illness were lower in 1996-1997 for patients receiving protease inhibitor therapy compared with those not receiving protease inhibitors. On balance, total health care payments tended to be slightly lower for patients receiving a protease inhibitor regimen. Although protease inhibitor-containing antiretroviral regimens are being used by only about half of our Medicaid-insured patients, when they are used, there are significantly lower hospital inpatient and community care costs, as well as lower costs associated with the treatment of opportunistic illness. Even with the concurrent increase in their pharmacy costs, total health care costs were stable or slightly lower for these patients. We believe this is a favorable result suggesting a good clinical value being achieved without an increase in costs.AIDS 05/1999; 13(8):963-9. · 6.24 Impact Factor
Enferm Infecc Microbiol Clin. 2012;30(8):458–462
Differences in the use of health resources by Spanish and immigrant
María Velasco∗, Virgilio Castilla, Carlos Guijarro, Leonor Moreno, Raquel Barba, Juan E. Losa
Infectious Diseases Section, Internal Medicine, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain
a r t i c l e i n f o
Received 19 January 2011
Accepted 5 January 2012
Available online 28 February 2012
a b s t r a c t
Background: HIV-immigrant use of health services and related cost has hardly been analysed. We
compared resource utilisation patterns and direct health care costs between Spanish and immigrant
Methods: All HIV-infected adult patients treated during the years 2003–2005 (372 patients) in this hos-
pital were included. We evaluated the number of out-patient, Emergency Room (ER) and Day-care Unit
visits, and number and length of admissions. Direct costs were analysed. We compared all variables
between immigrant and Spanish patients.
Results: Immigrants represented 12% (n=43) of the cohort. There were no differences in the number of
out-patient, ER, and day-care hospital visits per patient between both groups. The number of hospital
admissions per patient for any cause was higher in immigrant than in Spanish patients, 1.3 (4.4) ver-
sus 0.9 (2.7), P=.034. A high proportion of visits, both for the immigrant (45.1%) and Spanish patients
out-patient visits and ER visits were similar between groups. Pharmacy costs per year was higher in
Spanish patients than in immigrants (7351.8 versus 7153.9 euros [year 2005], P=.012). There were no
differences in the total cost per patient per year between both groups. The global distribution of cost
was very similar between both groups; almost 75% of the total cost was attributed to pharmacy in both
Conclusions: There are no significant differences in health resource utilisation and associated costs
between immigrant and Spanish HIV patients.
© 2011 Elsevier España, S.L. All rights reserved.
Diferencias en el uso de recursos sanitarios entre pacientes con infección VIH
espa˜ noles e inmigrantes
Infección por VIH
r e s u m e n
Introducción: La utilización y coste de los servicios sanitarios por parte de los pacientes inmigrantes con
infección por VIH apenas se ha estudiado. Se evaluó la asistencia sanitaria y su coste directo asociado
entre los pacientes con VIH espa˜ noles e inmigrantes.
Métodos: Se incluyeron todos los pacientes adultos infectados por el VIH atendidos durante los a˜ nos
2003-2005 (372 pacientes) en el hospital. Se evaluó el número de consultas, visitas a Urgencias (UR), a
todas las variables entre los inmigrantes y los espa˜ noles.
Resultados: Los inmigrantes representan un 12% (n = 43) de la cohorte. No hubo diferencias en el número
de consultas, visitas a UR y HD por paciente entre ambos grupos. El número de ingresos por cualquier
causa por paciente fue mayor en los inmigrantes que en los espa˜ noles, 1.3 (4.4) versus 0,9 (2,7), p =
0.034. Una alta proporción de consultas se realizaron en servicios diferentes de Infecciosas, tanto en
los inmigrantes (45,1%) como en los espa˜ noles (43,0%). Los costes medios por paciente fueron similares
en ambos grupos respecto a hospitalización, consulta y UR. El coste de farmacia por a˜ no fue mayor
en los espa˜ noles que los inmigrantes (7.351,8 D frente a 7,153.9 D [D a˜ no 2005], p = 0,012). No hubo
diferencias en el coste total por paciente por a˜ no entre ambos grupos. La distribución total del coste fue
muy similar entre ambos grupos; casi el 75% del coste total se atribuyó al tratamiento farmacológico en
E-mail address: email@example.com (M. Velasco).
0213-005X/$ – see front matter © 2011 Elsevier España, S.L. All rights reserved.
M. Velasco et al. / Enferm Infecc Microbiol Clin. 2012;30(8):458–462
Conclusiones: No hay diferencias significativas relevantes en la atención sanitaria y coste asociado entre
los pacientes con infección por VIH inmigrantes y espa˜ noles.
© 2011 Elsevier Espa˜ na, S.L. Todos los derechos reservados.
Immigration is a growing and relatively new phenomenon in
Spain. HIV-infected patients born abroad are an increasing propor-
tion of HIV patients treated in Spain. In some series, HIV-infected
immigrants reach almost 50% of the new HIV diagnosis.1
It is well known that a highly active antiretroviral therapy
Direct costs of HIV health care have been evaluated in the litera-
ture, especially after the introduction of HAART.2–4It is assumed
that immigrants may demand a higher use of healthcare services
because of socio-economic vulnerability. However, the specific
impact of the immigrant population with HIV infection on health
standing of healthcare use patterns is important for optimisation
of care and resource allocation.
This study was designed to compare resource use patterns
between immigrant and Spanish HIV-infected patients and to esti-
mate the direct health care costs of HIV/AIDS care in both groups
Patients and methods
All adult patients with HIV infection treated during the years
2003–2005 (from 01/01/2003 to 12/31/2005) in our institution
were included. HIV patients were actively identified by electronic
records. An immigrant was considered a patient not born in Spain.
Basic epidemiological data were registered for each patient: sex,
age, risk group, continent of origin, year of diagnosis of HIV infec-
tion, year of AIDS diagnosis, CDC classification at diagnosis of HIV,
description of first opportunistic disease, and mean CD4 count and
viral load during the period of the study.
centre and serves a population of about 250,000 inhabitants. All
types of HIV patients from this population are seen in our hospi-
tal. All major medical and surgical subspecialties are available on
both an inpatient and outpatient basis, except for cardiac and tho-
racic surgery, and neurosurgery. To provide care of patients with
HIV-infection, the hospital has an out-patient HIV clinic, and an
inpatient ward attended by Infectious Diseases experts associated
to Internal Medicine. Patients with HIV infection are hospitalised
according to the same physicians who provide medical care in the
out-patient clinic and they are treated during hospitalisation by
the same clinicians. Specific physicians belonging to Emergency
Room (ER) Department attend visits, and they occasionally decide
admissions as well.
resources and pharmaceutical costs during the period of the study.
Specifically, we evaluated the number of out-patient visits, both
scheduled and unscheduled, ER visits, visits to the Day-care Unit,
out-patient surgery, and number and length of admissions. Clinical
and health care information is registered in an electronic patient
record. For the purpose of this study, an episode was defined as
Unit visit, out-patient surgery and drug dispensation (Pharmacy).
All admissions to hospital for patients with HIV were included,
regardless of the admitting diagnosis. The clinical diagnosis corre-
sponding to hospital admissions was coded according to DRG [All
patient Diagnosis Related Groups (AP-DRGs) version 14th].
its. We included all out-patient visits (any speciality) and specific
Infectious Diseases visits. Other available out-patient resources
were Day-care Unit and out-patient surgery.
The Spanish healthcare system is open and free for all the
population. Reimbursement is based on health care activity: each
episode has an associated standardised cost according to disease
The cost of individual out-patient visits was calculated by the
officially assigned standard costs published by the Spanish Official
Health Authorities during the period of the study. Fees for first visit
visits scheduled, but not performed were not included.
group (DRG) was calculated from the standardised assigned cost
ish measure of hospitalisation cost regarding case-mix.7Case mix
is a standard and international measurement of the types of cases
being treated by a particular health care provider that is intended
to reflect the patients’ different needs for resources. The use of
these measurements allows comparison of performance and qual-
ity across organisations, practitioners, and communities. The HCU
is calculated using the means of the number, type, and severity
of illness of hospital admissions, and it is used for each hospi-
tal to allocate the cost of the admissions to the provider (Spanish
associated with patient care such as, physician fees, nursing care,
laboratory and diagnostic testing, and supplies, equipment, etc.
ER visits that ended as hospital admissions were included in the
hospitalisation cost (HCU). The HCU fee for the study period was
1425.8D, 1578.1D and 1741.0D for the years 2003, 2004 and 2005,
antiretroviral treatment dispensation every month. The cost of lab-
chemistry) was obtained from the standard rate. Total costs during
the period of the study were calculated by adding the cost of each
Unitary fees for ER were 80D for the years 2003–4 and 102D
(2005); and for Day-care hospital 323D (2003–4) and 393D (2005).
Cost per patient per year was calculated by adding the individual
cost of each episode each year and dividing it by the total number
of patients treated in the same period.
We performed a cost analysis from the health system perspec-
tive. In this study, only direct costs were included and the societal
perspective was not considered.8
We compared all variables between immigrant and Span-
ish patients. CD4 count was stratified: <200; 201–500 and
>500CD4cell/cc. Results are expressed by mean, standard devi-
ation and percentage as appropriate, and compared using the
chi-squared test for categorical variables, Student’s t-test for quan-
titative variables, and Mann–Whitney test for non-parametric
A multiple linear regression analysis was performed to estimate
the effect of immigration on the total health spending. We did
not find any interaction between variables, and a final model was
constituted by immigrant status and all confounding variables. In
M. Velasco et al. / Enferm Infecc Microbiol Clin. 2012;30(8):458–462
addition, the standardised total spending was calculated with the
means of the population and coefficients obtained in the multiple
linear regression analysis.
A total of 372 patients were seen during the period of study,
88% (n=329) Spanish. They were 24% women, mean age 40.3 (7.8)
the diagnosis of HIV, a total of 23.7% had AIDS. The most frequent
opportunistic diseases were extrapulmonary tuberculosis, pneu-
monia, and Pneumocystis jirovecii pneumonia. During the period of
the study, patients had a mean CD4 count of 466.2 (307.6)cell/cc
and viral load 2.4 (1.2)logcop/ml.
Immigrants represented 12% of the cohort (n=43), mean age
37.8 (11.5) years. The majority were women, 55.8%, and heterosex-
ual transmission was the main risk group, 81.4%. The continents
of origin were Africa 72%, Europe (East) 2.5%, and Central-South
On the contrary, Spanish patients were more frequently men,
24%, (P<.001 for the comparison with immigrants), with a similar
mean age, 40.5 (7.6) years (P=.311), and intravenous drug users,
were the main risk group (65%).
Mean time with HIV infection was lower for immigrant 1.9 (2.3)
years than Spanish patients 9.9 (6.0) years P<.001. Immigrants
showed a trend to a higher proportion of AIDS at the diagnosis of
HIV, 30.2% (P=.713). The most frequent opportunistic diseases for
immigrants were pulmonary tuberculosis, extrapulmonary tuber-
culosis, HIV encephalopathy, and wasting syndrome. During the
viral loads to Spanish patients: CD4 count 423.0 (252.9)cell/cc and
viral load 2.6 (1.3)log cop/ml.
The 372 patients generated a total of 9662 episodes of health
resource use, 88.6% (n=8509) by Spanish and 11.4% (n=1102) by
immigrant patients. All patients had more than one episode of
health resource use after HIV diagnosis. Among the 9662 episodes,
a very small number of them, n=158, corresponded to patients
without HIV diagnosis at the beginning of the study, so we did
not exclude these episodes from the analysis. In addition, fifty-one
episodes were difficult to classify and were excluded.
The number of hospital admissions per patient for any cause
was higher in immigrants than in Spanish patients (Table 1). There
were no differences in case-mix between immigrant and Span-
ish patients: mean case mix 2.2 (1.4) and 2.1 (1.5), respectively,
P=.755. The most frequent DRGs in immigrant patients were 709
(major diagnosis HIV related with major multiple diagnosis related
to tuberculosis), 710 (major diagnosis HIV related with major
Use of health care resources per patient during the 3 years of study. Data represent
of study. ID: Infectious Diseases. Pharmacy represents visits to Pharmacy.
ID Hospital admission
ID out-patient visits
Hospital Day Care
multiple diagnosis unrelated to tuberculosis) and 714 (HIV related
significant diagnosis). In Spanish patients, the most frequent DRGs
corresponded to 714, 710, 715 (HIV with other related diseases),
and also 542 (bronchitis and asthma with major complications),
206 (hepatic disease) and 541 (respiratory diseases and asthma).
Regarding out-patient clinic visits, a high proportion of them
(almost 50%), took place in services other than Infectious Diseases,
both for immigrant (45.1%) and Spanish (43%) patients. However,
grants were more frequently seen in Obstetrics and Oncology, and
Spànish patrients in Surgery, Dermatology and Gastroenterology
(Fig. 1). There was no difference in the number of out-patient visits
per patient between the groups (Table 1).
There was a tendency towards a lower number of ER visits
per patient in immigrants but it was not statistically significant
(Table 1). We did not find differences in the use of Day-care hos-
pital and Out-patient Surgery (Table 1) and these resources were
The proportional distribution of health resources usage in both
patient visits (more than 35%), but hospitalisation was more used
in immigrants (Fig. 2).
immigrant patients. In addition, there was no difference in the cost
of out-patient visits and ER visits per patient between both groups.
The cost of pharmacy per patient was slightly higher in Spanish
than in immigrant patients (Table 2).
There was no difference in the total cost per patient during the
3 years between immigrant (11,849D; 95% CI, 7173–15,056D) and
Spanish patients (10,957D; 95%CI, 7015–14,899)D.
The difference in costs (not adjusted) attributed to immigrants
was 893D (95% CI, −3784 to 4099)D.
Fig. 1. Distribution of out-patient clinic visits different of Infectious Diseases visits along the study. ORL: oto-rhino-laringology visits. GE: gastroenterology visits. G surgery:
M. Velasco et al. / Enferm Infecc Microbiol Clin. 2012;30(8):458–462
Fig. 2. Proportional distribution of healthcare usage of principal resources. The
graph represents the proportion of the number of times that different health
resources were used along the 3 years the study. Pharmacy represent visit to phar-
ferent health resources. Pharmacy includes all types of out-patient pharmacy drugs
delivered at Hospital Pharmacy (virtually all HAART and Hepatitis C treatment).
Spaniard (n=329) Immigrant (n=43)
Total associated cost
The adjusted overall cost for health care was 89.6D cheaper for
immigrants; 95% CI, −4710.4 to 4531.3; P=.969 (multiple linear
regression analysis). Variables included in the final model were:
sex, age, CD4 cell count, AIDS at diagnosis and time living with HIV
The overall distribution of cost was very similar between both
in both groups (Fig. 3).
In the present study, we have analysed the distribution of
resource use in immigrant and Spanish HIV patients, and we have
not found large differences in the overall pattern of usage. It has
been argued that immigrants make greater use of healthcare ser-
Even though, some studies have indicated that health services use
is lower among the immigrant population than among the host
population.9–11Our finding of similar healthcare use has special
Fig. 3. Distribution of global costs. Proportions represent the distribution of total
spending for all concepts along the 3 years of the study. ER: Emergency Room.
Pharmacy: Pharmacy includes all types of out-patient pharmacy drugs delivered
at Hospital Pharmacy (virtually all HAART and hepatitis C treatment).
relevance as this fact contradicts the expectation that immigrant
status leads to higher health resources consumption.
Access of care in Spain is public, free and universal, indepen-
specialised care presents several administrative barriers to irregu-
ish group (1.3 [4.4] versus 0.9 [2.7], P=.034). Several reasons may
underlie the higher proportion of hospitalisation in immigrants. A
lower perception of prevention, a delay in the diagnosis of HIV-
AIDS (higher proportion of immigrants than Spanish presented
with AIDS at the HIV diagnosis), and the use of health system when
real symptoms arise.12–14
although there were other reasons for hospitalisation more fre-
quently in the Spanish group. As previously reported, in the HAART
era, AIDS-defining conditions and diseases related to HIV continue
to have the highest hospitalisation rate among the diagnosis cate-
eases, as well stated in the literature.17This result emphasises the
importance of vaccination for pneumonia and influenza, as well as
prophylaxis for P. jirovecii. In addition, hospitalisation for reasons
other than AIDS conditions illustrates the importance of managing
comorbid conditions in this population.
A similar case mix was noted between the immigrant and Span-
ish group. A possible confounding factor is that hospitalisations
due to labour have a lower case mix, and are more frequent in
Immigrants exhibited a trend for a lower use of ER visits and
their associated costs. Although the differences did not reach
statistical significance, this should be interpreted with caution
given the low number of ER visits.
Similar healthcare usage by the immigrant and the Spanish-
born population may be attributable to the “survivor effect”, also
known as the “healthy immigration effect”, according to which
recently arrived immigrants have better health status than native-
Similar to another published study, a cross-sectional Spanish
National Health Survey, immigrants had similar diseases to those
pitalisation, although the investigators did not find evidence of
excessive and inappropriate use of other healthcare resources.20
Similarly, in a case-mix study from Spain, the resource usage
per discharge was lower among immigrants from low-income
An interesting finding in this work is the high proportion of
use of health care resources other than from Infectious Diseases
Unit in both groups. The clinical care of HIV patient has shifted to
include a higher proportion of other classical medical specialities
other than Infectious Diseases.7Of note, we found a different dis-
tribution of the specialities, with a prevalence of Obstetrics in the
The Spanish patients showed a slightly higher pharmacy usage.
This group of patients has a longer span of HIV infection, which
means more time on HAART, and consequently use more expen-
sive drug combinations. In spite of this, the total cost between the
tion did not affect this result. Similar access to HAART for both
previously published that access to HAART by foreign HIV patients
in Spain is similar to that of the Spanish population.23Pharmacy
made up two thirds of direct costs during the study, which bal-
ances the higher cost of hospitalisation in immigrants (23.5% of
M. Velasco et al. / Enferm Infecc Microbiol Clin. 2012;30(8):458–462
cost, Fig. 3). Similar figures have been shown in other European
An obvious limitation of our study is that immigrants are a
mobile population and the total number of patients may change
(actually increase). In any event, it is difficult to overpass the
weight of pharmacy usage with an increase of hospitalisation by
immigrants population. The number of patients is not high, but a
complete recording of all health resource consumption was per-
formed. We do no have data of entry into Spain, although we
do register data of HIV infection diagnosis and AIDS. Immigrants
with longer periods of stay in Spain may progress to a disease and
consumption pattern similar to the Spanish-born population. Fur-
more likely to have higher costs, as assessed in regression analysis.
In conclusion, we did not find significant differences in total
health resource consumption and associated cost between HIV
immigrant and Spanish HIV patients. A high proportion of health
care is provided by non-Infectious Diseases specialists in both
groups. Our study provides data to help in provision of services
to immigrant HIV patients.
and FIPSE 36690/07 (Fundación para la Investigación y Prevención
del SIDA en Espa˜ na), program of stabilisation of researchers 2007
from Instituto de Salud Carlos III (María Velasco) and funds from
Instituto Madrile˜ no de Salud, Comunidad Autónoma de Madrid.
Conflict of interest
The authors declare no conflict of interest.
We thank Dr Martin Ríos for critically reviewing the Methods
section of the manuscript.
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