Hydroxychloroquine (All indications except Antiphospholipid Syndrom)

Preterm (< 37 weeks)

R analysis
id Study   Lib. in paper Exposition period    Study type  Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S13648
R52923
Chambers (Controls unexposed, disease free), 2022 Preterm births (< 37 weeks’ gestation) at least 1st trimester prospective cohort unexposed, disease free excluded Adjustment: Yes Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) Matched 1.44 [0.63;3.31]
excluded (control group)
27/245   13/230 40 245
ref
S13649
R52939
Chambers (Controls unexposed, sick), 2022 Preterm births (< 37 weeks’ gestation) at least 1st trimester prospective cohort unexposed, sick Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) Matched 0.63 [0.39;1.03] 27/245   40/239 67 245
ref
S13666
R53065
Reynolds, 2022 Pre-term delivery at <38 weeks throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 1.23 [0.76;2.01] C 58/148   45/131 103 148
ref
S13670
R53107
Tang, 2022 Preterm birth (< 37 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: IgA nephropathy 0.93 [0.32;2.73] C 6/25   16/63 22 25
ref
S13676
R53139
Andersson (Controls exposed to corticosteroides), 2021 Preterm birth (< 37 completed gestational weeks) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Indication HCQ: Any or not specified Matched 0.72 [0.46;1.14]
excluded (control group)
38/293   50/293 88 293
ref
S13677
R53143
Andersson (Controls unexposed, NOS), 2021 Preterm birth (< 37 completed gestational weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: No Indication HCQ: Any or not specified Matched 1.51 [0.90;2.54] 39/298   27/298 66 298
ref
S13645
R52898
Bérard, 2021 Preterm birth (deliveries before the 37th week of gestation) during pregnancy (anytime or not specified) nested case control unexposed (general population or NOS) Adjustment: Yes Indication HCQ: Any or not specified 1.29 [0.67;2.50] 13/103   15,019/230,972 15,032 103
ref
S13769
R53868
Canti, 2021 Preterm delivery throughout pregnancy prospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.56 [0.17;1.86] C 7/39   7/25 14 39
ref
S13775
R53916
Liu, 2021 Preterm birth during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Indication HCQ: Systemic lupus erythematosus (SLE) Matched 1.11 [0.45;2.76] 14/40   13/40 27 40
ref
S13697
R53283
Louthrenoo, 2021 Prematurity during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.67 [0.23;1.93] 19/35   23/36 42 35
ref
S13707
R53366
Abd Rahman, 2020 Preterm livebirth (< 37 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.42 [0.15;1.18] C 11/37   14/28 25 37
ref
S13773
R53885
Baalbaki, 2020 Preterm birth <37 weeks during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.59 [0.24;1.50] C 19/47   16/30 35 47
ref
S13654
R53030
Do, 2020 Preterm delivery (<37 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE) 0.60 [0.20;1.40] 18/53   31/76 49 53
ref
S13695
R53278
Haase, 2020 Preterm birth (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE) 0.31 [0.15;0.64] 16/77   30/107 46 77
ref
S13713
R53410
Mollerach, 2019 Preterm (NOS) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 3.87 [0.07;205.70] C 0/12   0/45 0 12
ref
S13715
R53426
Seo, 2019 Late preterm (< 37 weeks’ gestation) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.73 [0.35;1.52] C 19/72   22/67 41 72
ref
S13699
R53333
Kroese, 2017 Preterm live birth (live birth < 37 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE) 0.50 [0.10;2.40] 2/20   16/68 18 20
ref
S13687
R53200
Leroux, 2015 Preterm birth (< 37 weeks of gestation) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.17 [0.05;0.63] 6/38   34/77 40 38
ref
S13651
R52963
Cooper (controls exposed to TNF-I), 2014 Preterm birth 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 1.60 [0.73;3.51] C
excluded (control group)
45/192   9/56 54 192
ref
S13652
R52993
Cooper (controls unexposed, sick), 2014 Preterm birth 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 1.29 [0.78;2.15] C 45/192   32/167 77 192
ref
S13679
R53152
Diav-Citrin, 2013 Preterm delivery (≤36 weeks) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 4.57 [2.58;8.09] C 27/95   33/413 60 95
ref
S13700
R53340
Al Arfaj, 2010 Preterm birth (before 37 weeks of gestation) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.53 [0.23;1.24] C 8/40   52/163 60 40
ref
S13672
R53116
Vroom (controls exposed to sulfasalazine), 2009 Premature birth (GA<37 weeks) 2nd trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes Indication HCQ: Any or not specified 2.49 [0.44;14.19]
excluded (control group)
2/16   9/169 11 16
ref
S13673
R53124
Vroom (controls unexposed, disease free), 2009 Premature birth (GA<37 weeks) 2nd trimester retrospective cohort (claims database) unexposed, disease free Adjustment: Yes Indication HCQ: Any or not specified 3.49 [0.80;15.32] 2/16   15,239/414,770 15,241 16
ref
S13650
R52954
Clowse, 2006 Preterm (20–36.9 weeks) throughout pregnancy prospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.92 [0.48;1.78] C 19/49   64/157 83 49
ref
S13702
R53355
Chakravarty, 2005 Prematurity (<37 weeks of gestational) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 1.10 [0.60;2.00] -/13   -/50 - 13
ref
S13671
R53114
Tincani, 2005 Premature birth (NOS) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indication HCQ: Connective tissue diseases (CTD) 1.39 [0.54;3.57] C 11/71   9/77 20 71
ref
S13653
R53023
Costedoat-Chalumeau, 2003 Premature birth (before 37 weeks’ gestation) throughout pregnancy prospective cohort unexposed, sick Adjustment: No Indication HCQ: Any or not specified 1.54 [0.73;3.26] C 33/117   12/59 45 117
ref
S13701
R53342
Buchanan, 1996 Prematurity (live birth between 21 and 37 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 1.33 [0.53;3.34] C 17/31   21/44 38 31
ref
Total 25 studies 0.94 [0.72;1.24] 31,251 1,913
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Chambers (Controls unexposed, sick), 2022Chambers, 2022 1 0.63[0.39; 1.03]672456%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Reynolds, 2022Reynolds, 2022 1.23[0.76; 2.01]1031486%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Tang, 2022Tang, 2022 0.93[0.32; 2.73]22253%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Andersson (Controls unexposed, NOS), 2021Andersson, 2021 2 1.51[0.90; 2.54]662986%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Bérard, 2021Bérard, 2021 1.29[0.67; 2.50]15,0321035%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Canti, 2021Canti, 2021 0.56[0.17; 1.86]14393%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Liu, 2021Liu, 2021 1.11[0.45; 2.76]27404%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Louthrenoo, 2021Louthrenoo, 2021 0.67[0.23; 1.93]42353%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Abd Rahman, 2020Abd Rahman, 2020 0.42[0.15; 1.18]25373%ROB confusion: criticalROB selection: criticalROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Baalbaki, 2020Baalbaki, 2020 0.59[0.24; 1.50]35474%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Do, 2020Do, 2020 0.60[0.20; 1.40]49534%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Haase, 2020Haase, 2020 0.31[0.15; 0.64]46775%ROB confusion: unclearROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: unclear Mollerach, 2019Mollerach, 2019 3.87[0.07; 205.70]0120%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Seo, 2019Seo, 2019 0.73[0.35; 1.52]41725%ROB confusion: seriousROB selection: lowROB classification: unclearROB missing: unclearROB mesure: moderateROB reporting: moderate Kroese, 2017Kroese, 2017 0.50[0.10; 2.40]18202%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Leroux, 2015Leroux, 2015 0.17[0.05; 0.63]40383%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Cooper (controls unexposed, sick), 2014Cooper, 2014 3 1.29[0.78; 2.15]771926%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Diav-Citrin, 2013Diav-Citrin, 2013 4.57[2.58; 8.09]60955%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Al Arfaj, 2010Al Arfaj, 2010 0.53[0.23; 1.24]60404%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Vroom (controls unexposed, disease free), 2009Vroom, 2009 4 3.49[0.80; 15.32]15,241162%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Clowse, 2006Clowse, 2006 0.92[0.48; 1.78]83495%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Chakravarty, 2005Chakravarty, 2005 1.10[0.60; 2.00]-135%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Tincani, 2005Tincani, 2005 1.39[0.54; 3.57]20714%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: moderateROB reporting: unclear Costedoat-Chalumeau, 2003Costedoat-Chalumeau, 2003 1.54[0.73; 3.26]451175%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Buchanan, 1996Buchanan, 1996 1.33[0.53; 3.34]38314%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (25 studies) I2 = 65% 0.94[0.72; 1.24]31,2511,9130.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, NOS; 3: controls unexposed, sick; 4: controls unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.93[0.70; 1.23]16,2191,81066%NAChambers (Controls unexposed, sick), 2022 Reynolds, 2022 Tang, 2022 Andersson (Controls unexposed, NOS), 2021 Canti, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Leroux, 2015 Cooper (controls unexposed, sick), 2014 Diav-Citrin, 2013 Al Arfaj, 2010 Vroom (controls unexposed, disease free), 2009 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 24 case control studiescase control studies 1.29[0.67; 2.49]15,032103 -NABérard, 2021 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.24[1.13; 4.41]30,39951273%NAAndersson (Controls unexposed, NOS), 2021 Bérard, 2021 Diav-Citrin, 2013 Vroom (controls unexposed, disease free), 2009 4 unexposed, sickunexposed, sick 0.80[0.64; 1.01]8521,40135%NAChambers (Controls unexposed, sick), 2022 Reynolds, 2022 Tang, 2022 Canti, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Leroux, 2015 Cooper (controls unexposed, sick), 2014 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 21 Tags Adjustment   - No  - No 0.98[0.73; 1.32]8381,60465%NAChambers (Controls unexposed, sick), 2022 Reynolds, 2022 Tang, 2022 Andersson (Controls unexposed, NOS), 2021 Canti, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Mollerach, 2019 Seo, 2019 Leroux, 2015 Cooper (controls unexposed, sick), 2014 Diav-Citrin, 2013 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 19   - Yes  - Yes 0.79[0.36; 1.74]30,38626969%NABérard, 2021 Do, 2020 Haase, 2020 Kroese, 2017 Vroom (controls unexposed, disease free), 2009 5 Indication HCQ   - Any or not specified  - Any or not specified 1.52[1.07; 2.15]30,3845340%NAAndersson (Controls unexposed, NOS), 2021 Bérard, 2021 Vroom (controls unexposed, disease free), 2009 Costedoat-Chalumeau, 2003 4   - Connective tissue diseases (CTD)  - Connective tissue diseases (CTD) 1.39[0.54; 3.57]2071 -NATincani, 2005 1   - IgA nephropathy  - IgA nephropathy 0.93[0.32; 2.73]2225 -NATang, 2022 1   - Rheumatic diseases as a whole (Syst ...  - Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 1.62[0.57; 4.64]20454489%NAChambers (Controls unexposed, sick), 2022 Mollerach, 2019 Cooper (controls unexposed, sick), 2014 Diav-Citrin, 2013 4   - Systemic lupus erythematosus (SLE)  - Systemic lupus erythematosus (SLE) 0.71[0.54; 0.93]62173935%NAReynolds, 2022 Canti, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Seo, 2019 Kroese, 2017 Leroux, 2015 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Buchanan, 1996 15 MatchedMatched 1.00[0.55; 1.83]16058366%NAChambers (Controls unexposed, sick), 2022 Andersson (Controls unexposed, NOS), 2021 Liu, 2021 3 All studiesAll studies 0.94[0.72; 1.24]31,2511,91365%NAChambers (Controls unexposed, sick), 2022 Reynolds, 2022 Tang, 2022 Andersson (Controls unexposed, NOS), 2021 Bérard, 2021 Canti, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Leroux, 2015 Cooper (controls unexposed, sick), 2014 Diav-Citrin, 2013 Al Arfaj, 2010 Vroom (controls unexposed, disease free), 2009 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 250.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.84.72.4330.000Chambers (Controls unexposed, sick), 2022Reynolds, 2022Tang, 2022Andersson (Controls unexposed, NOS), 2021Bérard, 2021Canti, 2021Liu, 2021Louthrenoo, 2021Abd Rahman, 2020Baalbaki, 2020Do, 2020Haase, 2020Mollerach, 2019Seo, 2019Kroese, 2017Leroux, 2015Cooper (controls unexposed, sick), 2014Diav-Citrin, 2013Al Arfaj, 2010Vroom (controls unexposed, disease free), 2009Clowse, 2006Chakravarty, 2005Tincani, 2005Costedoat-Chalumeau, 2003Buchanan, 1996

Asymetry test p-value = 0.1134 (by Egger's regression)

slope=0.4643 (0.3632); intercept=-1.2119 (0.9447); t=1.2828; p=0.1134

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 13672, 13651, 13676, 13648

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.05[1.17; 3.59]30,43975767%NAChambers (Controls unexposed, disease free), 2022 Andersson (Controls unexposed, NOS), 2021 Bérard, 2021 Diav-Citrin, 2013 Vroom (controls unexposed, disease free), 2009 5 unexposed, sick controlsunexposed, sick controls 0.80[0.64; 1.01]8521,40135%NAChambers (Controls unexposed, sick), 2022 Reynolds, 2022 Tang, 2022 Canti, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Leroux, 2015 Cooper (controls unexposed, sick), 2014 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 21 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.13[0.56; 2.29]15350153%NAAndersson (Controls exposed to corticosteroides), 2021 Cooper (controls exposed to TNF-I), 2014 Vroom (controls exposed to sulfasalazine), 2009 30.510.01.0

Umbrella review (other published meta-analyses)

Published MATE95% CIn exposedkI2Control groupExposition period Clowse (All SLE (lupus) pregnancies)Clowse (All SLE (lupus) pregnancies) 0.68[0.39; 1.18]NA-whatever (meta-analysis)during pregnancy (anytime or not specified)studies7 Duan (SLE indication)Duan (SLE indication) 0.55[0.36; 0.86]41%-unexposed, sickthroughout pregnancystudies8 Guillotin (SLE indication)Guillotin (SLE indication) 0.54[0.26; 1.15]54%-whatever (meta-analysis)throughout pregnancystudies6 Kaplan (All indications)Kaplan (All indications) 1.75[0.95; 3.24]72%-whatever (meta-analysis)at least 1st trimesterstudies5 Naveau (SLE indication)Naveau (SLE indication) 0.61[0.40; 0.93]47%-whatever (meta-analysis)during pregnancy (anytime or not specified)studies-9 Sperber (Autoimmune diseases)Sperber (Autoimmune diseases) 1.08[0.74; 1.57]0%-whatever (meta-analysis)during pregnancy (anytime or not specified)studies4 metaPregmetaPreg 0.94[0.72; 1.24]65%1,913--Chambers (Controls unexposed, sick), 2022 Reynolds, 2022 Tang, 2022 Andersson (Controls unexposed, NOS), 2021 Bérard, 2021 Canti, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Leroux, 2015 Cooper (controls unexposed, sick), 2014 Diav-Citrin, 2013 Al Arfaj, 2010 Vroom (controls unexposed, disease free), 2009 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 250.510.01.0