179
ORIGINAL ARTICLE
Frequency and Characteristics of Infectious Diseases in Internationally Adopted Children: A Retrospective Study in Nantes From 2010 to 2012 Fanny Hénaff, MD,∗ Isabelle Hazart, MD,† Georges Picherot, MD,† Françoise Baqué, MD,‡ Christèle Gras-Le Guen, MD, PhD,∗ and Elise Launay, MD† Urgences pédiatriques; † Service de Pédiatrie Communautaire, CHU Nantes, Hôpital Mère-Enfant, Nantes, France; ‡ Espace départemental adoption, Nantes, France
∗
DOI: 10.1111/jtm.12196
Background and Aims. Internationally adopted children are more susceptible to developing and carrying acute or chronic infectious diseases. Specialized consultations exist in the main French cities; however, specialized consultation with a pediatrician is not mandatory. The main objective of this study was to determine the frequency and characteristics of infections (bacterial, viral, and parasitic) among a group of international adoptees in Nantes over a 3-year period. Methods. A retrospective chart review was conducted of internationally adopted children who went through the Medical Guidance for Adopted Children Consultation between 2010 and 2012. Results. A total of 133 children were included in the study. Of these, 55% had an infectious disease; 8% were severe infections. We found a frequency of 38% [confidence interval (CI) 95% 30–46] for parasitic intestinal and 35% (CI 95% 27–43) for dermatologic infections. African children were more likely to have infections that required hospitalization [odds ratio (OR) = 12, p = 0.004, CI 95% 1.3–113.7] and more likely to carry extended-spectrum β-lactamase-producing bacteria. Conclusion. The frequency of infectious diseases, and sometimes severe diseases, found among our cohort of internationally adopted children highlights the need for systematic, specialized medical care.
E
ach year, many children (145 in 2010, 59 in 2011, and 55 in 2012) are internationally adopted in Loire-Atlantique, the department with the third highest rate of adoption in France.1 Indeed, France has the third largest number of international adoptees, after the United States and Italy, with 3,500 internationally adopted children in 2010, 2,000 in 2011, and 1,500 in 2012. Most of these children lived in orphanages or similar institutions in their country of origin and were more susceptible to developing and carrying infectious diseases,2 – 4 such as chronic viral diseases, tuberculosis, and parasitic infections. Therefore, medical care is essential when the child first arrives into the country to ensure the health3,5,6 of both the child and the family.7 – 9
Corresponding Author: Fanny Hénaff, MD, Urgences pédiatriques, CHU Nantes, Hôpital Mère-Enfant, 9 Quai Moncousu, F-44093 Nantes, France. E-mail: fanny.henaff@ gmail.com
In the United States, travel and adoption clinics exist that receive children in the first 6 weeks after their arrival. Crucially, this medical visit is strongly recommended and seems to be widespread.2 – 6,10,11 Since 1999, some specialized consultations, named Medical Guidance for Adopted Children Consultation (COCA in French), have operated in every region of France.12 – 15 These consultations take place in university hospitals and are guided by pediatricians, infectious disease specialists, or parasitic biologists. However, in contrast to the United States where it is strongly recommended, there are no rules in France that obligate the parents to consult a general practitioner (GP), pediatrician, or the COCA. The first medical checkup is not systematic, despite the advice from the adoption department of the county.16 Unfortunately, the importance of this checkup is underestimated by the GPs.15 Even if a checkup was performed in the adoptees’ country of origin, studies have shown that this information can be incomplete, badly translated, discordant, or that children often become infected after the checkup.2,9,15,17,18 © 2015 International Society of Travel Medicine, 1195-1982 Journal of Travel Medicine 2015; Volume 22 (Issue 3): 179–185
180
Only a few teams in France have reported data on the global state of health of internationally adopted children, and most of these were during the last decade,12,18,19 without any centralized coordination. One team published a preliminary survey concerning the global state of health of 170 internationally adopted children in France.19 Most of the literature comes from the United States.2 – 4,9,11 However, the population of adopted children in France is different from that in the United States. Indeed, each country has a different geographic profile of internationally adopted children. Therefore, one cannot extrapolate the findings from the United States to other countries.1,3,4 Medical problems in adopted children could vary according to their country of origin.3,5 One possibility is to mandate that medical checkups be adapted based on the country of origin of the adoptee. However, most medical studies focus only on simple pathology,17,20,21 the country of origin,22,23 or serology.10,24 Studies that detail all pathologies, infectious or not, are rare and outdated.8,25 Moreover, international adoption procedures change quickly, and information from before 2005 concerning adoption procedures and some parts of the medical reports is already obsolete. The main aim of this survey was to determine the frequency and characteristics of infections among international adoptees in Nantes over a 3-year period. The second objective was to gather demographic data (ie, country of origin, age, and living conditions in the native country) and correlate these with infections in the adoptees. This could provide improved information for future checkups and specialized consultations. Methods Study Design We performed a retrospective chart review of the University Hospital in Nantes between January 2010 and December 2012. The study was approved by the local ethics committee (Groupe Nantais d’Ethique dans le Domaine de la Santé). French Adoption Process In France, the first step for adoptive parents is to put in a request for adoption to the French administrative department where they live. Adoption is a time-consuming process and usually takes around 2 years. After filing for adoption, the parents must obtain approval and have meetings with the adoption department and social workers. Next, they can choose to adopt alone or through an organization—governmental or nongovernmental—and must then make another request to the chosen country. Once the request has been granted, they must go to the country to meet the child who has been nominated for them. Adoptive parents may have access, when available and depending on the adoption organization, to medical information about the child. They can then decide to ask for advice J Travel Med 2015; 22: 179–185
Hénaff et al.
from a pediatrician about the medical file during a pre-adoption consultation, which is strongly recommended by certain organizations but not mandatory. After the arrival of the child, the parents are free to consult with their own GP or a pediatrician outside the hospital, or they can consult with the COCA, which is the recommendation of the administrative department. Study Population All children under 16 years of age who had been seen through the COCA were included. Because this consultation was not an obligation, we asked the unit of the administrative county (Loire-Atlantique) that supervises adoption for the total number of children adopted in the department. We also included children who had a scheduled consultation but were hospitalized before the consultation could occur. There were no exclusion criteria in this retrospective study. Data Collection Pediatricians specializing in infectious diseases, endocrinology, or family medicine filled out a form during the consultation, which contained personal, clinical, and biological data. This form was part of the medical charts and was not specifically created for the present study. Demographic data were collected through the adoption file and through questioning the parents (age, country of origin, living conditions with a foster family or orphanage, and medical history if known). Every child received the same systematic screening tests (Table 1). Minor infections were defined as parasitic intestinal infections, dermatosis, or nonhospitalized bacterial intestinal infections. Severe infections were defined as bacterial infections that required hospitalization, tuberculosis, syphilis, malaria, or chronic viral infections [hepatitis B and hepatitis C viruses and human immunodeficiency virus (HIV)]. Statistical Analysis The quantitative data are presented as medians and an interquartile range (IQR). The qualitative data are expressed as percentages with a confidence interval of 95% (CI 95%). Frequency comparisons were done with the Chi-squared test or Fisher’s exact test depending on the effectiveness. The quantitative data were compared with a Student’s t-test (for normal distributions) or Mann–Whitney and Kruskal–Wallis tests (for all others). The determinants of infection were analyzed with a univariate analysis. The candidate variables were age of the child, country of origin, and living environment. Deviance from linearity was tested for the quantitative variables (age), and when observed, the variables were transformed to the lowest degree fractional polynoma and to categorical variables (deduced from the fractional polynoma). When a significant association was found in the univariate analysis (p < 0.1), the variable was entered into the multivariate analysis (a logistic regression). Statistical significance was defined as p < 0.05. Missing
181
Infections in Adopted Children Table 1
Screening examinations used by the COCA Searched pathology
Viral infections
Bacterial and mycobacterial infections
HIV Hepatitis C virus Hepatitis B virus
Hepatitis A virus Syphilis Digestive infection
Parasitic and mycotic infections
Urinary infection Tuberculosis Intestinal infection
Schistosomiasis Malaria Tinea infection Vaccinations Noninfectious diseases
Sickle-cell disease, hypo- or hyperthyroidism, iron deficiency, saturnism, real physiological age and early puberty
Tests
Systematic (yes/no)
ELISA, western blot Serology, liver balance Anti-HBs antibody, anti-HBs antigen, anti-HBc antibody, liver balance Serology, liver balance TPHA, VDRL
Y Y Y
Y Y
One stool examination, blood cell count Bacterial culture Tuberculin test and chest X-ray Three parasitic stool examinations with Baermann test, blood cell count Urinalyses, serology Blood smear, blood cell count Culture Tetanus, poliomyelitis, rubella serology Hemoglobin electrophoresis, iron balance, thyroid balance, blood lead level, bone age
N, if diarrhea Y Y Y, and Baermann test if needed for strongyloidosis N, if hypereosinophilia N, if fever N, if suspicion Y Y
HIV = human immunodeficiency virus; ELISA = enzyme-linked immunosorbent assay; HB = hepatitis B; TPHA = Treponema pallidum hemagglutination assay; VDRL = venereal disease research laboratory.
data were excluded. Statistical analyses were performed with STATA 11.0 (StataCorp 2009, College Station, TX, USA). Results Study Population A total of 133 children were seen by the COCA between 2010 and 2012. According to the administrative data for internationally adopted children, 145 children were adopted in Loire-Atlantique in 2010, 59 in 2011, and 55 in 2012. Therefore, the COCA received 30% of the children in 2010 and 2012 and 50% in 2011. The median interval from arrival to consultation was 54 days (IQR 24–178). The interval from arrival to consultation for the children with minor infections was 33 days (IQR 23–81) versus 155 days for those who did not have any infections (IQR 45–238). Either GPs or parents initiated the COCA referral. Table 2 presents the personal data pertaining to the adoptees’ country of origin. Most of the children came from Haiti, after the earthquake of January 2010 (67%, CI 95% 54–80). After Haiti, the most represented region was sub-Saharan Africa (Figure 1). The youngest children were 6 months old and the oldest were 9 years old. The median time spent in their native institutions was 1.5 years (range: 6 months to 7 years). Before arrival, 31% (CI 95% 23–39) of the children had a notable medical history: prematurity (eight children, two with fetal alcohol syndrome); infectious diseases [14
children, one with supposed neonatal tetanus, one with treated tuberculosis, and one with a urinary tract infection with extended-spectrum β-lactamase-producing (ESBL-producing) bacteria]; cardiac pathologies (four children); severe malnutrition (four children); and asthma (four children). Two children had cleft palates, which had been treated. The frequency of medical issues in the adoptees’ medical history was significantly different between the countries of origin of the children (Chi-squared, p < 0.001). Indeed, Russian and Colombian adoptees were more likely to have a past medical history (prematurity and malnutrition; Table 3). Minor Infectious Diseases About 55% (CI 95% 47–64) of the adoptees presented with an infectious disease. Intestinal parasitic infection was found in 47 children (38%, CI 95% 30–46). The median interval between arrival and consultation for these children was 33 days (IQR 21–86) versus 74 days (IQR 29–214) for those who did not have a parasitic infection. The most represented infection was giardiasis, which occurred in 41 children (33%, CI 95% 25–41), followed by infection with Hymenolepis nana that was observed in 14 children (11%, CI 95% 6–16). Another 14 children (10%, CI 95% 5–15) had a nonpathogenic Entamoeba coli amebiasis and two had a pathogenic amebiasis (Entamoeba histolytica). Three children presented with strongyloidosis: one with ascaridiosis, one with Taenia, and one with pinworm in the stool. Various parasites were found in the stool in 18 J Travel Med 2015; 22: 179–185
182 Table 2
Hénaff et al. Demographic data; absolute values (%)
Age Median (years) [IQR] 0–2 years 2–4 years >4 years Sex ratio M/F Living conditions Biological family Orphanage Foster family Hospital
Total (N = 133)
Haiti (N = 52)
South America* (N = 8)
Africa† (N = 46)
Asia‡ (N = 16)
Europe§ (N = 11)
2.7 [1.6–4.6] 52 (39) 37 (28) 44 (33) 1.5
3.6 [2.2–5] 11 (21) 18 (34) 23 (44) 1.7
4.6 [1.8–9] 3 (38) 1 (13) 4 (50) 3
1.6 [1–3.4] 28 (61) 10 (22) 8 (17) 1.1
1.8 [1.2–4.2] 8 (50) 4 (25) 4 (25) 1.3
3.4 [2.2–6.2] 2 (18) 4 (36) 5 (45) 1.8
5 (4) 116 (87) 8 (6) 1 (1)
3 (6) 48 (94) 0 0
0 2 (25) 6 (75) 0
2 (4) 41 (91) 1 (2) 1 (2)
0 14 (93) 1 (7) 0
0 11 (100) 0 0
p
ORIGINAL ARTICLE
Frequency and Characteristics of Infectious Diseases in Internationally Adopted Children: A Retrospective Study in Nantes From 2010 to 2012 Fanny Hénaff, MD,∗ Isabelle Hazart, MD,† Georges Picherot, MD,† Françoise Baqué, MD,‡ Christèle Gras-Le Guen, MD, PhD,∗ and Elise Launay, MD† Urgences pédiatriques; † Service de Pédiatrie Communautaire, CHU Nantes, Hôpital Mère-Enfant, Nantes, France; ‡ Espace départemental adoption, Nantes, France
∗
DOI: 10.1111/jtm.12196
Background and Aims. Internationally adopted children are more susceptible to developing and carrying acute or chronic infectious diseases. Specialized consultations exist in the main French cities; however, specialized consultation with a pediatrician is not mandatory. The main objective of this study was to determine the frequency and characteristics of infections (bacterial, viral, and parasitic) among a group of international adoptees in Nantes over a 3-year period. Methods. A retrospective chart review was conducted of internationally adopted children who went through the Medical Guidance for Adopted Children Consultation between 2010 and 2012. Results. A total of 133 children were included in the study. Of these, 55% had an infectious disease; 8% were severe infections. We found a frequency of 38% [confidence interval (CI) 95% 30–46] for parasitic intestinal and 35% (CI 95% 27–43) for dermatologic infections. African children were more likely to have infections that required hospitalization [odds ratio (OR) = 12, p = 0.004, CI 95% 1.3–113.7] and more likely to carry extended-spectrum β-lactamase-producing bacteria. Conclusion. The frequency of infectious diseases, and sometimes severe diseases, found among our cohort of internationally adopted children highlights the need for systematic, specialized medical care.
E
ach year, many children (145 in 2010, 59 in 2011, and 55 in 2012) are internationally adopted in Loire-Atlantique, the department with the third highest rate of adoption in France.1 Indeed, France has the third largest number of international adoptees, after the United States and Italy, with 3,500 internationally adopted children in 2010, 2,000 in 2011, and 1,500 in 2012. Most of these children lived in orphanages or similar institutions in their country of origin and were more susceptible to developing and carrying infectious diseases,2 – 4 such as chronic viral diseases, tuberculosis, and parasitic infections. Therefore, medical care is essential when the child first arrives into the country to ensure the health3,5,6 of both the child and the family.7 – 9
Corresponding Author: Fanny Hénaff, MD, Urgences pédiatriques, CHU Nantes, Hôpital Mère-Enfant, 9 Quai Moncousu, F-44093 Nantes, France. E-mail: fanny.henaff@ gmail.com
In the United States, travel and adoption clinics exist that receive children in the first 6 weeks after their arrival. Crucially, this medical visit is strongly recommended and seems to be widespread.2 – 6,10,11 Since 1999, some specialized consultations, named Medical Guidance for Adopted Children Consultation (COCA in French), have operated in every region of France.12 – 15 These consultations take place in university hospitals and are guided by pediatricians, infectious disease specialists, or parasitic biologists. However, in contrast to the United States where it is strongly recommended, there are no rules in France that obligate the parents to consult a general practitioner (GP), pediatrician, or the COCA. The first medical checkup is not systematic, despite the advice from the adoption department of the county.16 Unfortunately, the importance of this checkup is underestimated by the GPs.15 Even if a checkup was performed in the adoptees’ country of origin, studies have shown that this information can be incomplete, badly translated, discordant, or that children often become infected after the checkup.2,9,15,17,18 © 2015 International Society of Travel Medicine, 1195-1982 Journal of Travel Medicine 2015; Volume 22 (Issue 3): 179–185
180
Only a few teams in France have reported data on the global state of health of internationally adopted children, and most of these were during the last decade,12,18,19 without any centralized coordination. One team published a preliminary survey concerning the global state of health of 170 internationally adopted children in France.19 Most of the literature comes from the United States.2 – 4,9,11 However, the population of adopted children in France is different from that in the United States. Indeed, each country has a different geographic profile of internationally adopted children. Therefore, one cannot extrapolate the findings from the United States to other countries.1,3,4 Medical problems in adopted children could vary according to their country of origin.3,5 One possibility is to mandate that medical checkups be adapted based on the country of origin of the adoptee. However, most medical studies focus only on simple pathology,17,20,21 the country of origin,22,23 or serology.10,24 Studies that detail all pathologies, infectious or not, are rare and outdated.8,25 Moreover, international adoption procedures change quickly, and information from before 2005 concerning adoption procedures and some parts of the medical reports is already obsolete. The main aim of this survey was to determine the frequency and characteristics of infections among international adoptees in Nantes over a 3-year period. The second objective was to gather demographic data (ie, country of origin, age, and living conditions in the native country) and correlate these with infections in the adoptees. This could provide improved information for future checkups and specialized consultations. Methods Study Design We performed a retrospective chart review of the University Hospital in Nantes between January 2010 and December 2012. The study was approved by the local ethics committee (Groupe Nantais d’Ethique dans le Domaine de la Santé). French Adoption Process In France, the first step for adoptive parents is to put in a request for adoption to the French administrative department where they live. Adoption is a time-consuming process and usually takes around 2 years. After filing for adoption, the parents must obtain approval and have meetings with the adoption department and social workers. Next, they can choose to adopt alone or through an organization—governmental or nongovernmental—and must then make another request to the chosen country. Once the request has been granted, they must go to the country to meet the child who has been nominated for them. Adoptive parents may have access, when available and depending on the adoption organization, to medical information about the child. They can then decide to ask for advice J Travel Med 2015; 22: 179–185
Hénaff et al.
from a pediatrician about the medical file during a pre-adoption consultation, which is strongly recommended by certain organizations but not mandatory. After the arrival of the child, the parents are free to consult with their own GP or a pediatrician outside the hospital, or they can consult with the COCA, which is the recommendation of the administrative department. Study Population All children under 16 years of age who had been seen through the COCA were included. Because this consultation was not an obligation, we asked the unit of the administrative county (Loire-Atlantique) that supervises adoption for the total number of children adopted in the department. We also included children who had a scheduled consultation but were hospitalized before the consultation could occur. There were no exclusion criteria in this retrospective study. Data Collection Pediatricians specializing in infectious diseases, endocrinology, or family medicine filled out a form during the consultation, which contained personal, clinical, and biological data. This form was part of the medical charts and was not specifically created for the present study. Demographic data were collected through the adoption file and through questioning the parents (age, country of origin, living conditions with a foster family or orphanage, and medical history if known). Every child received the same systematic screening tests (Table 1). Minor infections were defined as parasitic intestinal infections, dermatosis, or nonhospitalized bacterial intestinal infections. Severe infections were defined as bacterial infections that required hospitalization, tuberculosis, syphilis, malaria, or chronic viral infections [hepatitis B and hepatitis C viruses and human immunodeficiency virus (HIV)]. Statistical Analysis The quantitative data are presented as medians and an interquartile range (IQR). The qualitative data are expressed as percentages with a confidence interval of 95% (CI 95%). Frequency comparisons were done with the Chi-squared test or Fisher’s exact test depending on the effectiveness. The quantitative data were compared with a Student’s t-test (for normal distributions) or Mann–Whitney and Kruskal–Wallis tests (for all others). The determinants of infection were analyzed with a univariate analysis. The candidate variables were age of the child, country of origin, and living environment. Deviance from linearity was tested for the quantitative variables (age), and when observed, the variables were transformed to the lowest degree fractional polynoma and to categorical variables (deduced from the fractional polynoma). When a significant association was found in the univariate analysis (p < 0.1), the variable was entered into the multivariate analysis (a logistic regression). Statistical significance was defined as p < 0.05. Missing
181
Infections in Adopted Children Table 1
Screening examinations used by the COCA Searched pathology
Viral infections
Bacterial and mycobacterial infections
HIV Hepatitis C virus Hepatitis B virus
Hepatitis A virus Syphilis Digestive infection
Parasitic and mycotic infections
Urinary infection Tuberculosis Intestinal infection
Schistosomiasis Malaria Tinea infection Vaccinations Noninfectious diseases
Sickle-cell disease, hypo- or hyperthyroidism, iron deficiency, saturnism, real physiological age and early puberty
Tests
Systematic (yes/no)
ELISA, western blot Serology, liver balance Anti-HBs antibody, anti-HBs antigen, anti-HBc antibody, liver balance Serology, liver balance TPHA, VDRL
Y Y Y
Y Y
One stool examination, blood cell count Bacterial culture Tuberculin test and chest X-ray Three parasitic stool examinations with Baermann test, blood cell count Urinalyses, serology Blood smear, blood cell count Culture Tetanus, poliomyelitis, rubella serology Hemoglobin electrophoresis, iron balance, thyroid balance, blood lead level, bone age
N, if diarrhea Y Y Y, and Baermann test if needed for strongyloidosis N, if hypereosinophilia N, if fever N, if suspicion Y Y
HIV = human immunodeficiency virus; ELISA = enzyme-linked immunosorbent assay; HB = hepatitis B; TPHA = Treponema pallidum hemagglutination assay; VDRL = venereal disease research laboratory.
data were excluded. Statistical analyses were performed with STATA 11.0 (StataCorp 2009, College Station, TX, USA). Results Study Population A total of 133 children were seen by the COCA between 2010 and 2012. According to the administrative data for internationally adopted children, 145 children were adopted in Loire-Atlantique in 2010, 59 in 2011, and 55 in 2012. Therefore, the COCA received 30% of the children in 2010 and 2012 and 50% in 2011. The median interval from arrival to consultation was 54 days (IQR 24–178). The interval from arrival to consultation for the children with minor infections was 33 days (IQR 23–81) versus 155 days for those who did not have any infections (IQR 45–238). Either GPs or parents initiated the COCA referral. Table 2 presents the personal data pertaining to the adoptees’ country of origin. Most of the children came from Haiti, after the earthquake of January 2010 (67%, CI 95% 54–80). After Haiti, the most represented region was sub-Saharan Africa (Figure 1). The youngest children were 6 months old and the oldest were 9 years old. The median time spent in their native institutions was 1.5 years (range: 6 months to 7 years). Before arrival, 31% (CI 95% 23–39) of the children had a notable medical history: prematurity (eight children, two with fetal alcohol syndrome); infectious diseases [14
children, one with supposed neonatal tetanus, one with treated tuberculosis, and one with a urinary tract infection with extended-spectrum β-lactamase-producing (ESBL-producing) bacteria]; cardiac pathologies (four children); severe malnutrition (four children); and asthma (four children). Two children had cleft palates, which had been treated. The frequency of medical issues in the adoptees’ medical history was significantly different between the countries of origin of the children (Chi-squared, p < 0.001). Indeed, Russian and Colombian adoptees were more likely to have a past medical history (prematurity and malnutrition; Table 3). Minor Infectious Diseases About 55% (CI 95% 47–64) of the adoptees presented with an infectious disease. Intestinal parasitic infection was found in 47 children (38%, CI 95% 30–46). The median interval between arrival and consultation for these children was 33 days (IQR 21–86) versus 74 days (IQR 29–214) for those who did not have a parasitic infection. The most represented infection was giardiasis, which occurred in 41 children (33%, CI 95% 25–41), followed by infection with Hymenolepis nana that was observed in 14 children (11%, CI 95% 6–16). Another 14 children (10%, CI 95% 5–15) had a nonpathogenic Entamoeba coli amebiasis and two had a pathogenic amebiasis (Entamoeba histolytica). Three children presented with strongyloidosis: one with ascaridiosis, one with Taenia, and one with pinworm in the stool. Various parasites were found in the stool in 18 J Travel Med 2015; 22: 179–185
182 Table 2
Hénaff et al. Demographic data; absolute values (%)
Age Median (years) [IQR] 0–2 years 2–4 years >4 years Sex ratio M/F Living conditions Biological family Orphanage Foster family Hospital
Total (N = 133)
Haiti (N = 52)
South America* (N = 8)
Africa† (N = 46)
Asia‡ (N = 16)
Europe§ (N = 11)
2.7 [1.6–4.6] 52 (39) 37 (28) 44 (33) 1.5
3.6 [2.2–5] 11 (21) 18 (34) 23 (44) 1.7
4.6 [1.8–9] 3 (38) 1 (13) 4 (50) 3
1.6 [1–3.4] 28 (61) 10 (22) 8 (17) 1.1
1.8 [1.2–4.2] 8 (50) 4 (25) 4 (25) 1.3
3.4 [2.2–6.2] 2 (18) 4 (36) 5 (45) 1.8
5 (4) 116 (87) 8 (6) 1 (1)
3 (6) 48 (94) 0 0
0 2 (25) 6 (75) 0
2 (4) 41 (91) 1 (2) 1 (2)
0 14 (93) 1 (7) 0
0 11 (100) 0 0
p
