Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study
Identifieur interne : 000003 ( PascalFrancis/Corpus ); précédent : 000002; suivant : 000004Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study
Auteurs : Ali S. Omrani ; Mustafa M. Saad ; Kamran Baig ; Abdelkarim Bahloul ; Mohammed Abdul-Matin ; Amal Y. Alaidaroos ; Ghaleb A. Almakhlafi ; Mohammed M. Albarrak ; Ziad A. Memish ; Ali M. AlbarrakSource :
- Lancet. Infectious diseases : (print) [ 1473-3099 ] ; 2014.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used X2 and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5 • 88 × 109/L [SD 3 • 95] vs 9 • 88 × 109/L [6 • 63]; p=0.023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0 • 004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0 • 54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4 • 32 g/L [SD 2 • 47] vs 2 • 14 g/L [1 • 90]; p=0 • 002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended.
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NO : | PASCAL 14-0276185 INIST |
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ET : | Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study |
AU : | OMRANI (Ali S.); SAAD (Mustafa M.); BAIG (Kamran); BAHLOUL (Abdelkarim); ABDUL-MATIN (Mohammed); ALAIDAROOS (Amal Y.); ALMAKHLAFI (Ghaleb A.); ALBARRAK (Mohammed M.); MEMISH (Ziad A.); ALBARRAK (Ali M.) |
AF : | Division of Infectious Diseases, Prince Sultan Military Medical City/Riyadh/Arabie Saoudite (1 aut., 2 aut., 4 aut., 6 aut., 10 aut.); Department of Infection Prevention and Control, Prince Sultan Military Medical City/Riyadh/Arabie Saoudite (3 aut., 6 aut.); Department of Medicine, Prince Sultan Military Medical City/Riyadh/Arabie Saoudite (5 aut.); Department of Critical Care, Prince Sultan Military Medical City/Riyadh/Arabie Saoudite (7 aut., 8 aut.); Al-Faisal University and Ministry of Health/Riyadh/Arabie Saoudite (9 aut.) |
DT : | Publication en série; Niveau analytique |
SO : | Lancet. Infectious diseases : (print); ISSN 1473-3099; Royaume-Uni; Da. 2014; Vol. 14; No. 11; Pp. 1090-1095; Bibl. 26 ref. |
LA : | Anglais |
EA : | Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used X2 and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5 • 88 × 109/L [SD 3 • 95] vs 9 • 88 × 109/L [6 • 63]; p=0.023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0 • 004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0 • 54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4 • 32 g/L [SD 2 • 47] vs 2 • 14 g/L [1 • 90]; p=0 • 002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended. |
CC : | 002B05C02C; 002B02S05 |
FD : | Ribavirine; Interféron alpha 2a; Etude cohorte; Coronavirus; Antiviral; Anticancéreux; Forme grave; Syndrome respiratoire du Moyen-Orient |
FG : | Coronaviridae; Nidovirales; Virus; Analogue de nucléoside; Cytokine; Pathologie de l'appareil respiratoire; Virose; Infection |
ED : | Ribavirin; Interferon alpha 2a; Cohort study; Coronavirus; Antiviral; Antineoplastic agent; Middle East respiratory syndrome |
EG : | Coronaviridae; Nidovirales; Virus; Nucleoside analog; Cytokine; Respiratory disease; Viral disease; Infection |
SD : | Ribavirina; Interferon alfa 2a; Estudio cohorte; Coronavirus; Antiviral; Anticanceroso |
LO : | INIST-27478.354000504575310230 |
ID : | 14-0276185 |
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<author><name sortKey="Albarrak, Ali M" sort="Albarrak, Ali M" uniqKey="Albarrak A" first="Ali M." last="Albarrak">Ali M. Albarrak</name>
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<series><title level="j" type="main">Lancet. Infectious diseases : (print)</title>
<title level="j" type="abbreviated">Lancet. Infect. dis. : (print)</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic agent</term>
<term>Antiviral</term>
<term>Cohort study</term>
<term>Coronavirus</term>
<term>Interferon alpha 2a</term>
<term>Middle East respiratory syndrome</term>
<term>Ribavirin</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Ribavirine</term>
<term>Interféron alpha 2a</term>
<term>Etude cohorte</term>
<term>Coronavirus</term>
<term>Antiviral</term>
<term>Anticancéreux</term>
<term>Forme grave</term>
<term>Syndrome respiratoire du Moyen-Orient</term>
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<front><div type="abstract" xml:lang="en">Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used X<sup>2</sup>
and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5 • 88 × 10<sup>9</sup>
/L [SD 3 • 95] vs 9 • 88 × 10<sup>9</sup>
/L [6 • 63]; p=0.023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0 • 004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0 • 54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4 • 32 g/L [SD 2 • 47] vs 2 • 14 g/L [1 • 90]; p=0 • 002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended.</div>
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<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Lancet. Infectious diseases : (print)</s0>
</fA64>
<fA66 i1="01"><s0>GBR</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used X<sup>2</sup>
and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5 • 88 × 10<sup>9</sup>
/L [SD 3 • 95] vs 9 • 88 × 10<sup>9</sup>
/L [6 • 63]; p=0.023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0 • 004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0 • 54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4 • 32 g/L [SD 2 • 47] vs 2 • 14 g/L [1 • 90]; p=0 • 002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B05C02C</s0>
</fC02>
<fC02 i1="02" i2="X"><s0>002B02S05</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Ribavirine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Ribavirin</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Ribavirina</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Interféron alpha 2a</s0>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Interferon alpha 2a</s0>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Interferon alfa 2a</s0>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Etude cohorte</s0>
<s5>07</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Cohort study</s0>
<s5>07</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Estudio cohorte</s0>
<s5>07</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Coronavirus</s0>
<s2>NW</s2>
<s5>10</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Coronavirus</s0>
<s2>NW</s2>
<s5>10</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Coronavirus</s0>
<s2>NW</s2>
<s5>10</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Antiviral</s0>
<s5>30</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Antiviral</s0>
<s5>30</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Antiviral</s0>
<s5>30</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Anticancéreux</s0>
<s5>31</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Antineoplastic agent</s0>
<s5>31</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Anticanceroso</s0>
<s5>31</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Forme grave</s0>
<s4>INC</s4>
<s5>86</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Syndrome respiratoire du Moyen-Orient</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Middle East respiratory syndrome</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Analogue de nucléoside</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Nucleoside analog</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Análogo nucleósido</s0>
<s5>37</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Cytokine</s0>
<s5>38</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Cytokine</s0>
<s5>38</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Citoquina</s0>
<s5>38</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Pathologie de l'appareil respiratoire</s0>
<s5>39</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Respiratory disease</s0>
<s5>39</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Aparato respiratorio patología</s0>
<s5>39</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Virose</s0>
<s5>40</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Viral disease</s0>
<s5>40</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Virosis</s0>
<s5>40</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Infection</s0>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Infection</s0>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Infección</s0>
</fC07>
<fN21><s1>349</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
<server><NO>PASCAL 14-0276185 INIST</NO>
<ET>Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study</ET>
<AU>OMRANI (Ali S.); SAAD (Mustafa M.); BAIG (Kamran); BAHLOUL (Abdelkarim); ABDUL-MATIN (Mohammed); ALAIDAROOS (Amal Y.); ALMAKHLAFI (Ghaleb A.); ALBARRAK (Mohammed M.); MEMISH (Ziad A.); ALBARRAK (Ali M.)</AU>
<AF>Division of Infectious Diseases, Prince Sultan Military Medical City/Riyadh/Arabie Saoudite (1 aut., 2 aut., 4 aut., 6 aut., 10 aut.); Department of Infection Prevention and Control, Prince Sultan Military Medical City/Riyadh/Arabie Saoudite (3 aut., 6 aut.); Department of Medicine, Prince Sultan Military Medical City/Riyadh/Arabie Saoudite (5 aut.); Department of Critical Care, Prince Sultan Military Medical City/Riyadh/Arabie Saoudite (7 aut., 8 aut.); Al-Faisal University and Ministry of Health/Riyadh/Arabie Saoudite (9 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Lancet. Infectious diseases : (print); ISSN 1473-3099; Royaume-Uni; Da. 2014; Vol. 14; No. 11; Pp. 1090-1095; Bibl. 26 ref.</SO>
<LA>Anglais</LA>
<EA>Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used X<sup>2</sup>
and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5 • 88 × 10<sup>9</sup>
/L [SD 3 • 95] vs 9 • 88 × 10<sup>9</sup>
/L [6 • 63]; p=0.023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0 • 004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0 • 54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4 • 32 g/L [SD 2 • 47] vs 2 • 14 g/L [1 • 90]; p=0 • 002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended.</EA>
<CC>002B05C02C; 002B02S05</CC>
<FD>Ribavirine; Interféron alpha 2a; Etude cohorte; Coronavirus; Antiviral; Anticancéreux; Forme grave; Syndrome respiratoire du Moyen-Orient</FD>
<FG>Coronaviridae; Nidovirales; Virus; Analogue de nucléoside; Cytokine; Pathologie de l'appareil respiratoire; Virose; Infection</FG>
<ED>Ribavirin; Interferon alpha 2a; Cohort study; Coronavirus; Antiviral; Antineoplastic agent; Middle East respiratory syndrome</ED>
<EG>Coronaviridae; Nidovirales; Virus; Nucleoside analog; Cytokine; Respiratory disease; Viral disease; Infection</EG>
<SD>Ribavirina; Interferon alfa 2a; Estudio cohorte; Coronavirus; Antiviral; Anticanceroso</SD>
<LO>INIST-27478.354000504575310230</LO>
<ID>14-0276185</ID>
</server>
</inist>
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