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HypoCCS: A Prospective Observational Study of Effect of Somatropin on Growth Hormone Deficient Adults

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01088399
Collaborator
(none)
10,673
Enrollment
123
Duration (Months)

Study Details

Study Description

Brief Summary

The Hypopituitary Control and Complications Study "HypoCCS" is a prospective, open label, global, multicentre, observational study on routine clinical care of adults with growth hormone deficiency occurring either isolated or in combination with other pituitary hormone deficiencies. The objective of this observational study is to evaluate long-term safety and health outcomes for adult growth hormone deficient participants with or without somatropin replacement therapy. As an observational study, data are collected only as provided at the discretion of the attending physician. The participant enrolled meet the criteria of growth hormone deficiency in adults as per the Humatrope label in the country where their attending physician practices, and this diagnosis is at the discretion of the attending physician. The decision to receive somatropin or remain untreated is made by the participant in consultation with their attending physician.

While treatment of adult growth hormone deficient participants with somatropin has been shown to be safe and effective in clinical trials of 18 months duration, this observational study aims to provide information on health outcome and replacement therapy over longer periods of time for a larger number of participants in the context of the overall disease environment.

Condition or Disease Intervention/Treatment Phase
  • Drug: Somatropin (rDNA origin)

Study Design

Study Type:
Observational
Actual Enrollment :
10673 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
The Global Hypopituitary Control and Complications Study
Study Start Date :
Sep 1, 2002
Actual Primary Completion Date :
Dec 1, 2012
Actual Study Completion Date :
Dec 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Somatropin replacement treatment

Adult participants with growth hormone deficiency receiving somatropin replacement treatment.

Drug: Somatropin (rDNA origin)
Dose, frequency and duration are at discretion of attending physician, and determined on an individual basis.
Other Names:
  • Humatrope
  • LY137998

    		•
    No treatment

    Adult participants with growth hormone deficiency receiving no somatropin replacement treatment.

    Outcome Measures

    Primary Outcome Measures

    1. Clinically Significant Adverse Events [Baseline to study completion (approximately 10 years)]

      A summary of all reported serious adverse events (SAE) and other adverse events regardless of causality are provided in the Adverse Events module of this record.

    Secondary Outcome Measures

    1. Cardiovascular Risk Factor-Change From Baseline in Body Mass Index (BMI) [Baseline, interim time point (5 years), and study completion (10 years)]

      Change in BMI was used as an indicator of cardiovascular risk. Body mass index (BMI) is an estimate of body fat based on body weight divided by height squared.

    2. Cardiovascular Risk Factor-Change From Baseline in Systolic (SBP) and Diastolic Blood Pressure (DBP) [Baseline, interim time point (5 years), and study completion (10 years)]

      Change in SBP and DBP were used as an indicator of cardiovascular risk.

    3. Cardiovascular Risk Factor-Change From Baseline in Cholesterol and Triglycerides [Baseline, interim time point (5 years), and study completion (10 years)]

      Change from baseline in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides were used as an indicator of cardiovascular risk and are presented.

    4. Cardiovascular Risk Factor-Change From Baseline in Waist Circumference [Baseline, interim time point (5 years), and study completion (10 years)]

      Change in waist circumference was used as an indicator of cardiovascular risk.

    5. Percentage of Participants Experiencing a Bone Fracture (Fracture Incidence) [Baseline through 10 years]

    6. Change From Baseline in the Total Z Score of the Disease-specific Module of the Questions of Life Satisfaction (QLS-H). [Baseline, interim time point (5 years), and study completion (10 years)]

      QLS-H is a self-administered, weighted, quality of life (QoL) questionnaire consisting of 9 items developed for participants with growth hormone deficiency. Scores were corrected for age, gender, and country differences, and expressed as Z-scores based on country-specific reference ranges. Participants indicate how important a certain dimension of QoL is to them and are then questioned as to their degree of satisfaction with that dimension. Each item is rated on a 5-point Likert scale ranging from not important (1) to extremely important (5) and from dissatisfied (1) to very satisfied (5). The weighted score for the degree of satisfaction (weighted satisfaction) with a particular dimension=(importance - 1)x(2 x satisfaction - 5). Total Z-score is obtained by adding the individual item scores of the 9 dimensions, and range from -108 (representing very low satisfaction) to +180 (representing very high satisfaction).

    Other Outcome Measures

    1. Number of Participants Who Died While in the Study [Study enrollment up to approximately 10 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Adult growth hormone deficiency as per the local Humatrope label and as judged by the attending physician
    Exclusion Criteria:
    • As per the local Humatrope label and as judged by the attending physician

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01088399
    Other Study ID Numbers:
    • 6448
    • B9R-MC-GDGA
    First Posted:
    Mar 17, 2010
    Last Update Posted:
    Apr 21, 2014
    Last Verified:
    Mar 1, 2014
    Additional relevant MeSH terms:
    Hypopituitarism

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Participants were initially enrolled in 2 regional observational studies (B9R-EW-GDDQ [GDDQ] initiated in 1997 and B9R-MC-GDEE [GDEE] in 1998) which were merged into the global Study B9R-MC-GDGA (GDGA, NCT01088399) in 2002. This record spans approximately 15 years from the initial enrollment in regional studies to completion of Study GDGA.
    Arm/Group Title Somatropin Treated Untreated
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants. It is not known whether participants did or did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
    Period Title: Overall Study
    STARTED 8716 1655 302
    COMPLETED 1595 308 21
    NOT COMPLETED 7121 1347 281

    Baseline Characteristics

    Arm/Group Title Somatropin Treated Untreated Unknown Total
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants. It is unknown whether participants did or did not receive somatropin therapy during the study. No form of intervention was imposed on the participants. Total of all reporting groups
    Overall Participants 8716 1655 302 10673
    Age, Customized (participants) [Number]
    <20 years
    421
    4.8%
    36
    2.2%
    10
    3.3%
    467
    4.4%
    20 years to <30 years
    1258
    14.4%
    152
    9.2%
    36
    11.9%
    1446
    13.5%
    30 years to <40 years
    1475
    16.9%
    173
    10.5%
    54
    17.9%
    1702
    15.9%
    40 years to <50 years
    1975
    22.7%
    318
    19.2%
    76
    25.2%
    2369
    22.2%
    50 years to <60 years
    2048
    23.5%
    379
    22.9%
    74
    24.5%
    2501
    23.4%
    60 years to <70 years
    1116
    12.8%
    324
    19.6%
    38
    12.6%
    1478
    13.8%
    >=70 years
    421
    4.8%
    272
    16.4%
    13
    4.3%
    706
    6.6%
    unknown
    2
    0%
    1
    0.1%
    1
    0.3%
    4
    0%
    Sex: Female, Male (Count of Participants)
    Female
    4158
    47.7%
    714
    43.1%
    155
    51.3%
    5027
    47.1%
    Male
    4558
    52.3%
    941
    56.9%
    147
    48.7%
    5646
    52.9%
    Race/Ethnicity, Customized (participants) [Number]
    African Descent
    226
    2.6%
    96
    5.8%
    14
    4.6%
    336
    3.1%
    Caucasian
    6058
    69.5%
    1080
    65.3%
    236
    78.1%
    7374
    69.1%
    East/Southeast Asian
    460
    5.3%
    129
    7.8%
    7
    2.3%
    596
    5.6%
    Hispanic
    153
    1.8%
    55
    3.3%
    16
    5.3%
    224
    2.1%
    Western Asian
    24
    0.3%
    5
    0.3%
    3
    1%
    32
    0.3%
    Other
    38
    0.4%
    10
    0.6%
    2
    0.7%
    50
    0.5%
    Declined To Provide
    387
    4.4%
    82
    5%
    12
    4%
    481
    4.5%
    Unknown
    1370
    15.7%
    198
    12%
    12
    4%
    1580
    14.8%
    Region of Enrollment (participants) [Number]
    Austria
    77
    0.9%
    1
    0.1%
    1
    0.3%
    79
    0.7%
    Belgium
    55
    0.6%
    1
    0.1%
    0
    0%
    56
    0.5%
    Canada
    63
    0.7%
    51
    3.1%
    0
    0%
    114
    1.1%
    Czech Republic
    77
    0.9%
    5
    0.3%
    0
    0%
    82
    0.8%
    Denmark
    151
    1.7%
    5
    0.3%
    0
    0%
    156
    1.5%
    France
    452
    5.2%
    218
    13.2%
    6
    2%
    676
    6.3%
    Germany
    553
    6.3%
    87
    5.3%
    19
    6.3%
    659
    6.2%
    Hungary
    102
    1.2%
    2
    0.1%
    0
    0%
    104
    1%
    Iceland
    10
    0.1%
    1
    0.1%
    1
    0.3%
    12
    0.1%
    Italy
    1242
    14.2%
    64
    3.9%
    49
    16.2%
    1355
    12.7%
    Japan
    407
    4.7%
    102
    6.2%
    0
    0%
    509
    4.8%
    Norway
    17
    0.2%
    0
    0%
    0
    0%
    17
    0.2%
    Spain
    427
    4.9%
    55
    3.3%
    2
    0.7%
    484
    4.5%
    Sweden
    355
    4.1%
    3
    0.2%
    2
    0.7%
    360
    3.4%
    Netherlands
    460
    5.3%
    1
    0.1%
    0
    0%
    461
    4.3%
    United Kingdom
    538
    6.2%
    15
    0.9%
    6
    2%
    559
    5.2%
    United States
    3730
    42.8%
    1044
    63.1%
    216
    71.5%
    4990
    46.8%
    Growth Hormone Deficiency (GHD) Onset Type (participants) [Number]
    Adult
    6968
    79.9%
    1422
    85.9%
    247
    81.8%
    8637
    80.9%
    Childhood
    1702
    19.5%
    194
    11.7%
    29
    9.6%
    1925
    18%
    Unknown
    46
    0.5%
    39
    2.4%
    26
    8.6%
    111
    1%
    Insulin-like Growth Factor-I (IGF-I) (micrograms per liter (mcg/L)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [micrograms per liter (mcg/L)]
    100.4
    (78.0)
    75.0
    (55.3)
    95.5
    (63.7)
    96.4
    (75.2)
    IGF-I Standard Deviations Score (SDS) (standard deviation scores) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [standard deviation scores]
    -2.72
    (2.23)
    -2.82
    (1.97)
    -2.39
    (2.03)
    -2.73
    (2.19)
    Maximum Growth Hormone (GH) Peak on Stimulation Test (nanograms per milliliter (ng/mL)) [Mean (Standard Deviation) ]
    GHRH + Arginine (Arg, n=1175, 103, 51, 1329)
    2.5
    (3.5)
    5.2
    (8.1)
    4.4
    (8.1)
    2.8
    (4.4)
    Any test except GHRH + Arg (n=6579;1178;168;7925)
    1.1
    (1.9)
    2.0
    (3.7)
    5.2
    (6.7)
    1.3
    (2.5)
    Body Mass Index (BMI) (kilograms per square meter (kg/m^2)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms per square meter (kg/m^2)]
    29.7
    (7.0)
    29.9
    (7.0)
    30.0
    (6.9)
    29.7
    (7.0)
    Diagnosis Leading to GHD (participants) [Number]
    Pituitary adenoma
    3769
    43.2%
    865
    52.3%
    79
    26.2%
    4713
    44.2%
    Craniopharyngioma
    973
    11.2%
    125
    7.6%
    24
    7.9%
    1122
    10.5%
    Other Tumor
    653
    7.5%
    137
    8.3%
    7
    2.3%
    797
    7.5%
    Idiopathic
    1381
    15.8%
    177
    10.7%
    88
    29.1%
    1646
    15.4%
    Pituitary hemorrhage/brain injury
    455
    5.2%
    59
    3.6%
    4
    1.3%
    518
    4.9%
    Other less common specified diagnoses
    1027
    11.8%
    198
    12%
    79
    26.2%
    1304
    12.2%
    Causes other than listed above
    458
    5.3%
    94
    5.7%
    21
    7%
    573
    5.4%

    Outcome Measures

    1. Primary Outcome
    Title Clinically Significant Adverse Events
    Description A summary of all reported serious adverse events (SAE) and other adverse events regardless of causality are provided in the Adverse Events module of this record.
    Time Frame Baseline to study completion (approximately 10 years)

    Outcome Measure Data

    Analysis Population Description
    All participants with baseline and at least 1 post-baseline visit whose study therapy was known (treated or untreated).
    Arm/Group Title Somatropin Treated Untreated
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
    Measure Participants 8420 1269
    Death
    2.58
    0%
    3.78
    0.2%
    Malignancy
    4.0
    0%
    5.3
    0.3%
    Myocardial Infarction
    0.8
    0%
    1.4
    0.1%
    2. Secondary Outcome
    Title Cardiovascular Risk Factor-Change From Baseline in Body Mass Index (BMI)
    Description Change in BMI was used as an indicator of cardiovascular risk. Body mass index (BMI) is an estimate of body fat based on body weight divided by height squared.
    Time Frame Baseline, interim time point (5 years), and study completion (10 years)

    Outcome Measure Data

    Analysis Population Description
    All participants with baseline and at least 1 post-baseline visit whose study therapy was known (treated or untreated) and had BMI data.
    Arm/Group Title Somatropin Treated Untreated
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
    Measure Participants 8263 1452
    Change in BMI at 5 years (n=2541, 218)
    0.63
    (3.15)
    -0.10
    (3.25)
    Change in BMI at 10 years (n=884, 64)
    1.14
    (3.67)
    -0.32
    (2.67)
    3. Secondary Outcome
    Title Cardiovascular Risk Factor-Change From Baseline in Systolic (SBP) and Diastolic Blood Pressure (DBP)
    Description Change in SBP and DBP were used as an indicator of cardiovascular risk.
    Time Frame Baseline, interim time point (5 years), and study completion (10 years)

    Outcome Measure Data

    Analysis Population Description
    All participants with baseline and at least 1 post-baseline visit whose study therapy was known (treated or untreated) and BP data.
    Arm/Group Title Somatropin Treated Untreated
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
    Measure Participants 8258 1546
    Change in SBP at 5 years (n=2746, 272)
    1.04
    (17.49)
    -0.48
    (18.88)
    Change in SBP at 10 years (n=960, 73)
    1.98
    (18.81)
    3.71
    (20.04)
    Change in DBP at 5 years (n=2740, 272)
    -0.85
    (11.11)
    -0.76
    (11.71)
    Change in DBP at 10 years (n=955, 73)
    -1.23
    (11.85)
    -2.84
    (13.37)
    4. Secondary Outcome
    Title Cardiovascular Risk Factor-Change From Baseline in Cholesterol and Triglycerides
    Description Change from baseline in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides were used as an indicator of cardiovascular risk and are presented.
    Time Frame Baseline, interim time point (5 years), and study completion (10 years)

    Outcome Measure Data

    Analysis Population Description
    All participants with baseline and at least 1 post-baseline visit whose study therapy was known (treated or untreated) and had cholesterol or triglyceride data.
    Arm/Group Title Somatropin Treated Untreated
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
    Measure Participants 6327 1171
    Change in TC at 5 years (n=1865, 184)
    -13.0
    (45.74)
    -14.6
    (46.02)
    Change in TC at 10 years (n=668, 56)
    -17.9
    (52.87)
    -43.1
    (55.81)
    Change in HDL-C at 5 years (n=1667, 176)
    1.47
    (16.67)
    -0.54
    (13.82)
    Change in HDL-C at 10 years (n=615, 51)
    5.00
    (17.40)
    0.39
    (14.70)
    Change in LDL-C at 5 years (1435, 166)
    -10.7
    (41.32)
    -11.5
    (35.91)
    Change in LDL-C at 10 years (n=522, 47)
    -16.4
    (44.05)
    -29.3
    (41.44)
    Change in Triglycerides at 5 years (n=1581, 178)
    -9.51
    (99.67)
    -0.85
    (115.7)
    Change in Triglycerides at 10 years (n=571, 51)
    -16.4
    (107.8)
    -55.8
    (90.12)
    5. Secondary Outcome
    Title Cardiovascular Risk Factor-Change From Baseline in Waist Circumference
    Description Change in waist circumference was used as an indicator of cardiovascular risk.
    Time Frame Baseline, interim time point (5 years), and study completion (10 years)

    Outcome Measure Data

    Analysis Population Description
    All participants with baseline and at least 1 post-baseline visit whose study therapy was known (treated or untreated) and had waste circumference data.
    Arm/Group Title Somatropin Treated Untreated
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
    Measure Participants 6263 1005
    Change in circumference at 5 years (n=1719, 133)
    0.85
    (9.06)
    0.10
    (8.52)
    Change in circumference at 10 years (n=610, 34)
    3.57
    (10.22)
    3.03
    (7.76)
    6. Secondary Outcome
    Title Percentage of Participants Experiencing a Bone Fracture (Fracture Incidence)
    Description
    Time Frame Baseline through 10 years

    Outcome Measure Data

    Analysis Population Description
    All participants with baseline and at least 1 post-baseline visit and who provided bone fracture information.
    Arm/Group Title Somatropin Treated Untreated Unknown
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants. It is unknown whether participants did or did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
    Measure Participants 8420 1269 4
    Number [percentage of participants]
    3.75
    0%
    4.02
    0.2%
    0.00
    0%
    7. Secondary Outcome
    Title Change From Baseline in the Total Z Score of the Disease-specific Module of the Questions of Life Satisfaction (QLS-H).
    Description QLS-H is a self-administered, weighted, quality of life (QoL) questionnaire consisting of 9 items developed for participants with growth hormone deficiency. Scores were corrected for age, gender, and country differences, and expressed as Z-scores based on country-specific reference ranges. Participants indicate how important a certain dimension of QoL is to them and are then questioned as to their degree of satisfaction with that dimension. Each item is rated on a 5-point Likert scale ranging from not important (1) to extremely important (5) and from dissatisfied (1) to very satisfied (5). The weighted score for the degree of satisfaction (weighted satisfaction) with a particular dimension=(importance - 1)x(2 x satisfaction - 5). Total Z-score is obtained by adding the individual item scores of the 9 dimensions, and range from -108 (representing very low satisfaction) to +180 (representing very high satisfaction).
    Time Frame Baseline, interim time point (5 years), and study completion (10 years)

    Outcome Measure Data

    Analysis Population Description
    All participants with baseline and at least 1 post-baseline visit whose study therapy was known (treated or untreated) and has a Total Z Score.
    Arm/Group Title Somatropin Treated Untreated
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
    Measure Participants 2142 332
    Change in Total Z score at 5 years (n=475, 39)
    0.70
    (1.46)
    0.21
    (1.14)
    Change in Total Z score at 10 years (n=103, 3)
    0.53
    (1.39)
    -1.01
    (1.49)
    8. Other Pre-specified Outcome
    Title Number of Participants Who Died While in the Study
    Description
    Time Frame Study enrollment up to approximately 10 years

    Outcome Measure Data

    Analysis Population Description
    All participants with baseline and at least 1 post-baseline visit.
    Arm/Group Title Somatropin Treated Untreated Unknown
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants. It is unknown whether participants did or did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
    Measure Participants 8420 1269 4
    Number [participants]
    229
    2.6%
    50
    3%
    0
    0%

    Adverse Events

    Time Frame Study enrollment up to approximately 10 years.
    Adverse Event Reporting Description All participants with baseline and at least 1 post-baseline visit.
    Arm/Group Title Somatropin Treated Untreated
    Arm/Group Description Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants. Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants. It is unknown whether participants did or did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
    All Cause Mortality
    Somatropin Treated Untreated
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Somatropin Treated Untreated
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1602/8420 (19%) 288/1269 (22.7%) 0/4 (0%)
    Blood and lymphatic system disorders
    Agranulocytosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Anaemia 10/8420 (0.1%) 10 5/1269 (0.4%) 5 0/4 (0%) 0
    Anaemia of chronic disease 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Disseminated intravascular coagulation 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Febrile neutropenia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Haemorrhagic anaemia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Idiopathic thrombocytopenic purpura 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Iron deficiency anaemia 6/8420 (0.1%) 6 1/1269 (0.1%) 1 0/4 (0%) 0
    Leukocytosis 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Leukopenia 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Lymphadenopathy 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Neutrophilia 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Pancytopenia 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Thrombocytopenia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cardiac disorders
    Acute coronary syndrome 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Acute myocardial infarction 13/8420 (0.2%) 13 2/1269 (0.2%) 2 0/4 (0%) 0
    Angina pectoris 16/8420 (0.2%) 17 0/1269 (0%) 0 0/4 (0%) 0
    Angina unstable 7/8420 (0.1%) 7 2/1269 (0.2%) 2 0/4 (0%) 0
    Aortic valve incompetence 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Aortic valve stenosis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Arrhythmia 6/8420 (0.1%) 6 1/1269 (0.1%) 1 0/4 (0%) 0
    Arteriosclerosis coronary artery 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Atrial fibrillation 26/8420 (0.3%) 28 11/1269 (0.9%) 13 0/4 (0%) 0
    Atrial flutter 4/8420 (0%) 4 3/1269 (0.2%) 3 0/4 (0%) 0
    Atrial tachycardia 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Atrioventricular dissociation 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Bradycardia 5/8420 (0.1%) 5 4/1269 (0.3%) 4 0/4 (0%) 0
    Bundle branch block left 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Cardiac arrest 13/8420 (0.2%) 13 3/1269 (0.2%) 3 0/4 (0%) 0
    Cardiac failure 13/8420 (0.2%) 15 1/1269 (0.1%) 1 0/4 (0%) 0
    Cardiac failure acute 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cardiac failure congestive 19/8420 (0.2%) 22 10/1269 (0.8%) 11 0/4 (0%) 0
    Cardiac tamponade 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Cardio-respiratory arrest 3/8420 (0%) 3 4/1269 (0.3%) 4 0/4 (0%) 0
    Cardiomegaly 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Cardiomyopathy 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Coronary artery disease 22/8420 (0.3%) 23 7/1269 (0.6%) 7 0/4 (0%) 0
    Coronary artery occlusion 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Coronary artery stenosis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Cyanosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypertrophic cardiomyopathy 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Intracardiac thrombus 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ischaemic cardiomyopathy 1/8420 (0%) 1 2/1269 (0.2%) 2 0/4 (0%) 0
    Left ventricular dysfunction 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Left ventricular failure 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Mitral valve incompetence 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Myocardial infarction 39/8420 (0.5%) 41 12/1269 (0.9%) 13 0/4 (0%) 0
    Myocardial ischaemia 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Myocarditis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Palpitations 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Pericardial effusion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pericarditis 6/8420 (0.1%) 7 2/1269 (0.2%) 2 0/4 (0%) 0
    Right ventricular failure 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Sick sinus syndrome 3/8420 (0%) 3 2/1269 (0.2%) 2 0/4 (0%) 0
    Sinus bradycardia 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Subendocardial ischaemia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Supraventricular extrasystoles 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Supraventricular tachycardia 1/8420 (0%) 1 2/1269 (0.2%) 2 0/4 (0%) 0
    Tachyarrhythmia 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Tachycardia 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Ventricular fibrillation 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Ventricular hypertrophy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ventricular tachycardia 6/8420 (0.1%) 6 1/1269 (0.1%) 1 0/4 (0%) 0
    Wolff-parkinson-white syndrome 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Congenital, familial and genetic disorders
    Arnold-chiari malformation 2/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Arteriovenous malformation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Diencephalic syndrome of infancy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Dysmorphism 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gene mutation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Porphyria 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ear and labyrinth disorders
    Deafness unilateral 1/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Endolymphatic hydrops 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Hypoacusis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Meniere's disease 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Sudden hearing loss 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Tinnitus 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Vertigo 5/8420 (0.1%) 5 2/1269 (0.2%) 2 0/4 (0%) 0
    Endocrine disorders
    Addison's disease 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Adrenal disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Adrenal insufficiency 29/8420 (0.3%) 29 4/1269 (0.3%) 4 0/4 (0%) 0
    Adrenocortical insufficiency acute 54/8420 (0.6%) 62 6/1269 (0.5%) 7 0/4 (0%) 0
    Autoimmune thyroiditis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Carcinoid syndrome 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Diabetes insipidus 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Goitre 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Hyperadrenocorticism 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hyperprolactinaemia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypophysitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypopituitarism 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Hypothalamo-pituitary disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypothyroidism 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Inappropriate antidiuretic hormone secretion 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Lymphocytic hypophysitis 5/8420 (0.1%) 7 0/1269 (0%) 0 0/4 (0%) 0
    Nelson's syndrome 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pituitary cyst 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Pituitary enlargement 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pituitary haemorrhage 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Pituitary-dependent cushing's syndrome 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Secondary adrenocortical insufficiency 11/8420 (0.1%) 12 1/1269 (0.1%) 1 0/4 (0%) 0
    Eye disorders
    Blindness 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Blindness unilateral 1/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Cataract 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Diplopia 4/8420 (0%) 4 1/1269 (0.1%) 1 0/4 (0%) 0
    Eye pain 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Keratitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Retinal haemorrhage 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Retinal vein occlusion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Retinal vein thrombosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Scotoma 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Vision blurred 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Visual acuity reduced 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Visual impairment 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Vitreous detachment 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Gastrointestinal disorders
    Abdominal adhesions 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Abdominal discomfort 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Abdominal distension 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Abdominal hernia 3/8420 (0%) 3 2/1269 (0.2%) 2 0/4 (0%) 0
    Abdominal pain 21/8420 (0.2%) 22 3/1269 (0.2%) 3 0/4 (0%) 0
    Abdominal pain lower 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Abdominal pain upper 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Anal fissure 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Anal fistula 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Appendix disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ascites 2/8420 (0%) 2 2/1269 (0.2%) 2 0/4 (0%) 0
    Barrett's oesophagus 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Colitis 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Colitis ischaemic 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Colitis ulcerative 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Colonic polyp 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Constipation 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Crohn's disease 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Dental caries 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Diabetic enteropathy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Diaphragmatic hernia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Diarrhoea 29/8420 (0.3%) 30 7/1269 (0.6%) 7 0/4 (0%) 0
    Diverticular perforation 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Diverticulum 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Diverticulum intestinal 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Duodenal perforation 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Duodenal ulcer 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Duodenal ulcer perforation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Duodenitis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Dyspepsia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Enteritis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Enterocolitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Erosive oesophagitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Faecal incontinence 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Faecaloma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Food poisoning 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Gastric ulcer 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Gastric ulcer haemorrhage 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Gastritis 6/8420 (0.1%) 6 2/1269 (0.2%) 2 0/4 (0%) 0
    Gastritis erosive 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gastrointestinal disorder 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Gastrointestinal haemorrhage 12/8420 (0.1%) 13 4/1269 (0.3%) 4 0/4 (0%) 0
    Gastrointestinal necrosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gastrointestinal pain 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gastrooesophageal reflux disease 6/8420 (0.1%) 6 0/1269 (0%) 0 0/4 (0%) 0
    Haematochezia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Haemorrhoids 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Hiatus hernia 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Hyperchlorhydria 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ileitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ileus 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Impaired gastric emptying 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Inguinal hernia 6/8420 (0.1%) 7 0/1269 (0%) 0 0/4 (0%) 0
    Intestinal obstruction 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Intestinal perforation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Intestinal polyp 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Irritable bowel syndrome 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Large intestine perforation 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Lip ulceration 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lower gastrointestinal haemorrhage 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Mallory-weiss syndrome 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Melaena 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Mesenteric occlusion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Mesenteric vein thrombosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Nausea 33/8420 (0.4%) 35 4/1269 (0.3%) 4 0/4 (0%) 0
    Oesophageal dilatation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Oesophageal ulcer 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Oesophagitis 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Pancreatic necrosis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Pancreatitis 7/8420 (0.1%) 9 4/1269 (0.3%) 4 0/4 (0%) 0
    Pancreatitis acute 6/8420 (0.1%) 6 0/1269 (0%) 0 0/4 (0%) 0
    Pancreatitis necrotising 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Peritoneal adhesions 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Rectal haemorrhage 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Rectal polyp 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Rectal prolapse 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Salivary gland mass 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Small intestinal obstruction 7/8420 (0.1%) 8 2/1269 (0.2%) 3 0/4 (0%) 0
    Stomatitis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Subileus 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Umbilical hernia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Umbilical hernia, obstructive 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Upper gastrointestinal haemorrhage 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Varices oesophageal 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Volvulus 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Vomiting 38/8420 (0.5%) 45 4/1269 (0.3%) 4 0/4 (0%) 0
    General disorders
    Adverse drug reaction 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Asthenia 11/8420 (0.1%) 13 4/1269 (0.3%) 4 0/4 (0%) 0
    Chest discomfort 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Chest pain 37/8420 (0.4%) 41 9/1269 (0.7%) 9 0/4 (0%) 0
    Chills 1/8420 (0%) 1 2/1269 (0.2%) 2 0/4 (0%) 0
    Cyst 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Death 48/8420 (0.6%) 48 15/1269 (1.2%) 15 0/4 (0%) 0
    Device failure 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Device malfunction 1/8420 (0%) 1 1/1269 (0.1%) 2 0/4 (0%) 0
    Drug intolerance 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Fatigue 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Fibrosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gait disturbance 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    General physical health deterioration 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Haemorrhagic cyst 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Hernia 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Hernia obstructive 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hyperpyrexia 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Hyperthermia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypothermia 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Impaired healing 1/8420 (0%) 1 2/1269 (0.2%) 3 0/4 (0%) 0
    Implant site irritation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Inflammation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Influenza like illness 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Malaise 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Medical device pain 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Multi-organ disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Multi-organ failure 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Non-cardiac chest pain 10/8420 (0.1%) 14 3/1269 (0.2%) 3 0/4 (0%) 0
    Oedema 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Oedema peripheral 3/8420 (0%) 3 3/1269 (0.2%) 3 0/4 (0%) 0
    Pain 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Polyp 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pseudocyst 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Pyrexia 27/8420 (0.3%) 28 7/1269 (0.6%) 8 0/4 (0%) 0
    Sudden cardiac death 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Sudden death 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Systemic inflammatory response syndrome 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hepatobiliary disorders
    Bile duct stenosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bile duct stone 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Biliary colic 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Biliary dilatation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cholangitis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Cholecystitis 8/8420 (0.1%) 8 3/1269 (0.2%) 3 0/4 (0%) 0
    Cholecystitis acute 4/8420 (0%) 4 1/1269 (0.1%) 1 0/4 (0%) 0
    Cholelithiasis 21/8420 (0.2%) 21 4/1269 (0.3%) 4 0/4 (0%) 0
    Cholestasis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Chronic hepatic failure 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Gallbladder disorder 2/8420 (0%) 3 2/1269 (0.2%) 2 0/4 (0%) 0
    Hepatic cirrhosis 2/8420 (0%) 2 2/1269 (0.2%) 2 0/4 (0%) 0
    Hepatic failure 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hepatic steatosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hepatitis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Hepatotoxicity 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Jaundice 1/8420 (0%) 1 2/1269 (0.2%) 2 0/4 (0%) 0
    Immune system disorders
    Drug hypersensitivity 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Food allergy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypersensitivity 1/8420 (0%) 1 2/1269 (0.2%) 2 0/4 (0%) 0
    Sarcoidosis 5/8420 (0.1%) 7 0/1269 (0%) 0 0/4 (0%) 0
    Infections and infestations
    Abdominal abscess 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Abdominal sepsis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Abdominal wall infection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Abscess 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Abscess intestinal 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Abscess limb 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Abscess oral 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Acute sinusitis 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Appendiceal abscess 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Appendicitis 12/8420 (0.1%) 12 5/1269 (0.4%) 5 0/4 (0%) 0
    Arthritis bacterial 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Arthritis infective 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Atypical mycobacterial infection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bacterial sepsis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Breast cellulitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bronchitis 11/8420 (0.1%) 11 6/1269 (0.5%) 7 0/4 (0%) 0
    Bronchitis viral 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bronchopneumonia 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Bursitis infective 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Campylobacter infection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Candidiasis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cellulitis 19/8420 (0.2%) 27 4/1269 (0.3%) 5 0/4 (0%) 0
    Chronic sinusitis 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Clostridial infection 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Clostridium difficile colitis 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Colostomy infection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Corneal abscess 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Creutzfeldt-jakob disease 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Cystitis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Cystitis klebsiella 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cytomegalovirus hepatitis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Cytomegalovirus mononucleosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Device related infection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Device related sepsis 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Diarrhoea infectious 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Diverticulitis 16/8420 (0.2%) 19 3/1269 (0.2%) 4 0/4 (0%) 0
    Echinococciasis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Empyema 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Encephalitic infection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Encephalitis viral 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Endocarditis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Enteritis infectious 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Enterocolitis infectious 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Erysipelas 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Escherichia urinary tract infection 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Extradural abscess 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Gallbladder empyema 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gastroenteritis 43/8420 (0.5%) 45 5/1269 (0.4%) 8 0/4 (0%) 0
    Gastroenteritis salmonella 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Gastroenteritis viral 13/8420 (0.2%) 14 3/1269 (0.2%) 5 0/4 (0%) 0
    Gastrointestinal candidiasis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gastrointestinal infection 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Groin abscess 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Helicobacter gastritis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Herpes zoster 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Incision site cellulitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Infection 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Infectious mononucleosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Infectious peritonitis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Influenza 15/8420 (0.2%) 15 5/1269 (0.4%) 5 0/4 (0%) 0
    Infusion site infection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Intervertebral discitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Joint abscess 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Kidney infection 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Labyrinthitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lobar pneumonia 4/8420 (0%) 4 1/1269 (0.1%) 1 0/4 (0%) 0
    Localised infection 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Lower respiratory tract infection 5/8420 (0.1%) 9 2/1269 (0.2%) 2 0/4 (0%) 0
    Lung infection pseudomonal 1/8420 (0%) 1 2/1269 (0.2%) 2 0/4 (0%) 0
    Meningitis 7/8420 (0.1%) 7 3/1269 (0.2%) 3 0/4 (0%) 0
    Meningitis aseptic 1/8420 (0%) 1 2/1269 (0.2%) 2 0/4 (0%) 0
    Meningitis bacterial 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Meningitis viral 6/8420 (0.1%) 7 0/1269 (0%) 0 0/4 (0%) 0
    Meningoencephalitis bacterial 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Mycobacterium avium complex infection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Nasopharyngitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Necrotising fasciitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Oral candidiasis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Osteomyelitis 3/8420 (0%) 4 2/1269 (0.2%) 2 0/4 (0%) 0
    Pelvic abscess 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Peritonitis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Peritonsillar abscess 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pharyngitis 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Pharyngitis streptococcal 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pneumococcal sepsis 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Pneumonia 95/8420 (1.1%) 107 23/1269 (1.8%) 28 0/4 (0%) 0
    Pneumonia bacterial 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Pneumonia herpes viral 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pneumonia klebsiella 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Pneumonia pneumococcal 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Pneumonia viral 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Post procedural infection 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Post procedural pneumonia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pseudomonas infection 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Psoas abscess 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Purulent discharge 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pyelonephritis 4/8420 (0%) 4 1/1269 (0.1%) 1 0/4 (0%) 0
    Rectal abscess 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Respiratory tract infection 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Sepsis 26/8420 (0.3%) 26 8/1269 (0.6%) 8 0/4 (0%) 0
    Septic shock 7/8420 (0.1%) 7 5/1269 (0.4%) 5 0/4 (0%) 0
    Shunt infection 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Sinusitis 9/8420 (0.1%) 9 1/1269 (0.1%) 1 0/4 (0%) 0
    Skin infection 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Staphylococcal bacteraemia 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Staphylococcal infection 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Staphylococcal sepsis 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Subacute endocarditis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Subcutaneous abscess 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Tonsillitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Upper respiratory tract infection 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Upper respiratory tract infection bacterial 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Urinary tract infection 22/8420 (0.3%) 26 7/1269 (0.6%) 8 0/4 (0%) 0
    Urosepsis 9/8420 (0.1%) 11 2/1269 (0.2%) 3 0/4 (0%) 0
    Viraemia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Viral infection 16/8420 (0.2%) 16 4/1269 (0.3%) 4 0/4 (0%) 0
    Viral pericarditis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Viral upper respiratory tract infection 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Wound infection 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Wound infection staphylococcal 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Accident 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Accidental overdose 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Acetabulum fracture 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Alcohol poisoning 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Ankle fracture 7/8420 (0.1%) 7 2/1269 (0.2%) 2 0/4 (0%) 0
    Arterial injury 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Back injury 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Burns second degree 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Burns third degree 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Carbon monoxide poisoning 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cartilage injury 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cervical vertebral fracture 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Chest injury 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Clavicle fracture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Compression fracture 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Concussion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Contusion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Coronary artery restenosis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Craniocerebral injury 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Delayed effects of radiation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Dislocation of vertebra 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Extradural haematoma 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Facial bones fracture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Fall 28/8420 (0.3%) 28 5/1269 (0.4%) 5 0/4 (0%) 0
    Femoral neck fracture 5/8420 (0.1%) 6 0/1269 (0%) 0 0/4 (0%) 0
    Femur fracture 7/8420 (0.1%) 8 3/1269 (0.2%) 3 0/4 (0%) 0
    Fibula fracture 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Foot fracture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Forearm fracture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Fracture 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Graft complication 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Hand fracture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Head injury 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Heat exhaustion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Heat stroke 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hip fracture 8/8420 (0.1%) 8 1/1269 (0.1%) 1 0/4 (0%) 0
    Humerus fracture 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Injury 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Intentional overdose 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Joint dislocation 4/8420 (0%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Joint dislocation postoperative 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Laceration 8/8420 (0.1%) 8 1/1269 (0.1%) 1 0/4 (0%) 0
    Ligament injury 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ligament sprain 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Limb crushing injury 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Limb injury 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lower limb fracture 6/8420 (0.1%) 7 1/1269 (0.1%) 1 0/4 (0%) 0
    Lumbar vertebral fracture 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Maternal exposure during pregnancy 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Meningitis chemical 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Meniscus lesion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Mountain sickness acute 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Multiple fractures 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Multiple injuries 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Muscle rupture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Open wound 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Overdose 9/8420 (0.1%) 9 0/1269 (0%) 0 0/4 (0%) 0
    Pelvic fracture 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Poisoning deliberate 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Post lumbar puncture syndrome 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Post procedural complication 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Post procedural discharge 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Postoperative adhesion 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Postoperative fever 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Postoperative ileus 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Procedural pain 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Pubis fracture 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Radius fracture 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Rib fracture 3/8420 (0%) 3 2/1269 (0.2%) 2 0/4 (0%) 0
    Road traffic accident 15/8420 (0.2%) 15 2/1269 (0.2%) 2 0/4 (0%) 0
    Scapula fracture 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Seroma 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Skull fracture 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Spinal compression fracture 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Spinal fracture 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Splenic rupture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Sternal fracture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Subdural haematoma 3/8420 (0%) 3 2/1269 (0.2%) 2 0/4 (0%) 0
    Tendon rupture 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Thoracic vertebral fracture 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Tibia fracture 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Toxicity to various agents 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Traumatic fracture 6/8420 (0.1%) 6 0/1269 (0%) 0 0/4 (0%) 0
    Traumatic haematoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Traumatic liver injury 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Traumatic lung injury 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Upper limb fracture 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Uterine rupture 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Vascular pseudoaneurysm 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Wound dehiscence 0/8420 (0%) 0 2/1269 (0.2%) 2 0/4 (0%) 0
    Wrist fracture 1/8420 (0%) 1 2/1269 (0.2%) 3 0/4 (0%) 0
    Investigations
    Amniotic fluid volume increased 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Anticoagulation drug level below therapeutic 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Aspiration bone marrow 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Aspiration pleural cavity 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Band neutrophil count increased 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Blood cortisol decreased 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Blood cortisol increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Blood creatine phosphokinase increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Blood creatinine increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Blood electrolytes abnormal 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Blood glucose increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Blood potassium decreased 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Blood pressure increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Blood sodium decreased 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Bone density decreased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bronchoscopy 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Cardiac enzymes increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cortisol free urine increased 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Drug level below therapeutic 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Drug level increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Electrocardiogram 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Electrocardiogram change 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Endoscopy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Haematocrit increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Heart rate increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Heart rate irregular 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Hepatic enzyme increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hysteroscopy 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Immunosuppressant drug level decreased 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Lipase increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Liver function test abnormal 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Nuclear magnetic resonance imaging brain abnormal 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Prostatic specific antigen increased 1/4394 (0%) 1 0/745 (0%) 0 0/2 (0%) 0
    Smear cervix abnormal 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Ureteroscopy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Weight decreased 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Dehydration 44/8420 (0.5%) 48 16/1269 (1.3%) 18 0/4 (0%) 0
    Diabetes mellitus 15/8420 (0.2%) 15 2/1269 (0.2%) 2 0/4 (0%) 0
    Diabetes mellitus inadequate control 0/8420 (0%) 0 2/1269 (0.2%) 4 0/4 (0%) 0
    Diabetic complication 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Diabetic ketoacidosis 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Electrolyte imbalance 5/8420 (0.1%) 5 2/1269 (0.2%) 2 0/4 (0%) 0
    Failure to thrive 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Fluid retention 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gout 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypercalcaemia 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Hyperglycaemia 9/8420 (0.1%) 9 0/1269 (0%) 0 0/4 (0%) 0
    Hyperglycaemic hyperosmolar nonketotic syndrome 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Hyperkalaemia 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Hypernatraemia 5/8420 (0.1%) 6 3/1269 (0.2%) 3 0/4 (0%) 0
    Hypocalcaemia 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Hypoglycaemia 13/8420 (0.2%) 17 4/1269 (0.3%) 4 0/4 (0%) 0
    Hypokalaemia 11/8420 (0.1%) 12 1/1269 (0.1%) 1 0/4 (0%) 0
    Hyponatraemia 35/8420 (0.4%) 44 11/1269 (0.9%) 12 0/4 (0%) 0
    Hypophosphataemia 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Hypovolaemia 2/8420 (0%) 3 2/1269 (0.2%) 2 0/4 (0%) 0
    Lactic acidosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Malnutrition 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Metabolic acidosis 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Metabolic alkalosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Metabolic disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Obesity 0/8420 (0%) 0 3/1269 (0.2%) 3 0/4 (0%) 0
    Type 1 diabetes mellitus 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Type 2 diabetes mellitus 8/8420 (0.1%) 9 1/1269 (0.1%) 1 0/4 (0%) 0
    Musculoskeletal and connective tissue disorders
    Ankylosing spondylitis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Arthralgia 6/8420 (0.1%) 7 1/1269 (0.1%) 1 0/4 (0%) 0
    Arthritis 4/8420 (0%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Arthritis reactive 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Arthropathy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Back disorder 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Back pain 7/8420 (0.1%) 7 1/1269 (0.1%) 1 0/4 (0%) 0
    Bone disorder 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Bursitis 2/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Cervical spinal stenosis 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Chondrocalcinosis pyrophosphate 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Chondropathy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Costochondritis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Epiphysiolysis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Exostosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Fibromyalgia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Fistula 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Flank pain 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Foot deformity 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Fracture nonunion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hip deformity 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Intervertebral disc degeneration 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Intervertebral disc disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Intervertebral disc protrusion 20/8420 (0.2%) 21 2/1269 (0.2%) 2 0/4 (0%) 0
    Joint swelling 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lumbar spinal stenosis 2/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Muscle spasms 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Muscle twitching 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Muscular weakness 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Musculoskeletal chest pain 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Musculoskeletal pain 6/8420 (0.1%) 6 2/1269 (0.2%) 2 0/4 (0%) 0
    Myalgia 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Neck pain 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Neuropathic arthropathy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Osteitis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Osteoarthritis 20/8420 (0.2%) 25 5/1269 (0.4%) 5 0/4 (0%) 0
    Osteolysis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Osteonecrosis 6/8420 (0.1%) 7 1/1269 (0.1%) 1 0/4 (0%) 0
    Osteoporosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pain in extremity 3/8420 (0%) 3 3/1269 (0.2%) 3 0/4 (0%) 0
    Pain in jaw 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pathological fracture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pelvic deformity 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Polymyalgia rheumatica 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Rhabdomyolysis 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Rotator cuff syndrome 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Scoliosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Spinal column stenosis 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Spinal osteoarthritis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Systemic sclerosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Tendonitis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Acute myeloid leukaemia 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Adenocarcinoma 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Adenocarcinoma pancreas 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Adenoma benign 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Angiomyolipoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Astrocytoma 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    B-cell lymphoma 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    B-cell lymphoma stage iv 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    B-cell small lymphocytic lymphoma 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Basal cell carcinoma 18/8420 (0.2%) 22 4/1269 (0.3%) 5 0/4 (0%) 0
    Benign neoplasm of testis 1/4394 (0%) 1 0/745 (0%) 0 0/2 (0%) 0
    Benign neoplasm of thyroid gland 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Benign oesophageal neoplasm 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Benign ovarian tumour 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Benign respiratory tract neoplasm 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bladder cancer 4/8420 (0%) 4 1/1269 (0.1%) 1 0/4 (0%) 0
    Bladder neoplasm 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Bladder transitional cell carcinoma 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Bladder transitional cell carcinoma recurrent 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Brain neoplasm 4/8420 (0%) 4 1/1269 (0.1%) 1 0/4 (0%) 0
    Brain neoplasm malignant 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Breast cancer 16/8420 (0.2%) 16 1/1269 (0.1%) 1 0/4 (0%) 0
    Breast cancer female 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Breast cancer in situ 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Breast neoplasm 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bronchial carcinoma 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Carcinoid tumour 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Carcinoid tumour pulmonary 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Carotid body tumour 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Chronic myeloid leukaemia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cns germinoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Colon cancer 6/8420 (0.1%) 7 3/1269 (0.2%) 3 0/4 (0%) 0
    Colon cancer metastatic 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Colon cancer stage 0 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Colon cancer stage ii 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Colon neoplasm 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Colorectal cancer 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Craniopharyngioma 13/8420 (0.2%) 13 0/1269 (0%) 0 0/4 (0%) 0
    Craniopharyngioma benign 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Dermatofibrosarcoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Endometrial cancer 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Endometrial cancer stage i 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Ewing's sarcoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Fibroadenoma of breast 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gastric cancer 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Gastrointestinal carcinoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gastrointestinal stromal tumour 1/8420 (0%) 1 2/1269 (0.2%) 2 0/4 (0%) 0
    Germ cell cancer 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Glioblastoma 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Glioblastoma multiforme 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Glioma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Haemangioma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hepatic adenoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hepatic neoplasm malignant 0/8420 (0%) 0 2/1269 (0.2%) 2 0/4 (0%) 0
    Large intestine carcinoma 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Laryngeal cancer 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Lentigo maligna 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Leukaemia recurrent 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lip and/or oral cavity cancer 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lip neoplasm malignant stage unspecified 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lung adenocarcinoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lung adenocarcinoma stage iv 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lung cancer metastatic 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lung neoplasm 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Lung neoplasm malignant 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Lung squamous cell carcinoma stage unspecified 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lymphoma 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Malignant glioma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Malignant melanoma 11/8420 (0.1%) 11 0/1269 (0%) 0 0/4 (0%) 0
    Malignant melanoma in situ 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Malignant neoplasm of islets of langerhans 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Malignant soft tissue neoplasm 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Mantle cell lymphoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Mantle cell lymphoma recurrent 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Medulloblastoma recurrent 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Meningioma 21/8420 (0.2%) 23 0/1269 (0%) 0 0/4 (0%) 0
    Metastases to liver 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Metastases to lung 1/8420 (0%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Metastases to spine 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Metastatic malignant melanoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Metastatic renal cell carcinoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Mixed oligo-astrocytoma 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Multiple myeloma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Neoplasm 11/8420 (0.1%) 11 1/1269 (0.1%) 1 0/4 (0%) 0
    Neoplasm malignant 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Neoplasm prostate 1/4394 (0%) 1 0/745 (0%) 0 0/2 (0%) 0
    Neoplasm recurrence 8/8420 (0.1%) 8 1/1269 (0.1%) 1 0/4 (0%) 0
    Neoplasm skin 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Neurilemmoma benign 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Neurofibroma 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Non-hodgkin's lymphoma 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Non-hodgkin's lymphoma stage ii 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Non-secretory adenoma of pituitary 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Non-small cell lung cancer metastatic 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Optic nerve neoplasm 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ovarian adenoma 2/4025 (0%) 2 0/524 (0%) 0 0/2 (0%) 0
    Ovarian cancer 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Ovarian fibroma 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Pancreatic carcinoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pancreatic carcinoma metastatic 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pancreatic sarcoma 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Penis carcinoma 0/4394 (0%) 0 1/745 (0.1%) 1 0/2 (0%) 0
    Pharyngeal cancer stage unspecified 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pituitary tumour 5/8420 (0.1%) 6 3/1269 (0.2%) 3 0/4 (0%) 0
    Pituitary tumour benign 24/8420 (0.3%) 24 8/1269 (0.6%) 9 0/4 (0%) 0
    Pituitary tumour recurrent 115/8420 (1.4%) 128 19/1269 (1.5%) 19 0/4 (0%) 0
    Plasmacytoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pleural mesothelioma 1/8420 (0%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Pleural neoplasm 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Polycythaemia vera 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Prostate cancer 33/4394 (0.8%) 36 10/745 (1.3%) 10 0/2 (0%) 0
    Prostate cancer metastatic 1/4394 (0%) 1 0/745 (0%) 0 0/2 (0%) 0
    Prostatic adenoma 1/4394 (0%) 1 0/745 (0%) 0 0/2 (0%) 0
    Rectal cancer 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Renal cancer 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Renal cell carcinoma 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Renal neoplasm 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Renal oncocytoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Rhabdomyosarcoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Salivary gland adenoma 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Secretory adenoma of pituitary 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Squamous cell carcinoma 3/8420 (0%) 4 2/1269 (0.2%) 2 0/4 (0%) 0
    Squamous cell carcinoma of skin 2/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Thyroid adenoma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Thyroid cancer 13/8420 (0.2%) 13 1/1269 (0.1%) 1 0/4 (0%) 0
    Transitional cell carcinoma 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Tumour flare 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Tumour haemorrhage 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Uterine cancer 2/4025 (0%) 2 0/524 (0%) 0 0/2 (0%) 0
    Uterine leiomyoma 3/4025 (0.1%) 3 0/524 (0%) 0 0/2 (0%) 0
    Nervous system disorders
    Amnesia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Amyotrophic lateral sclerosis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Aphasia 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Ataxia 0/8420 (0%) 0 2/1269 (0.2%) 2 0/4 (0%) 0
    Balance disorder 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Basilar artery thrombosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Brain stem haemorrhage 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Brain stem infarction 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Carotid aneurysm rupture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Carotid artery aneurysm 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Carotid artery occlusion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Carotid artery stenosis 7/8420 (0.1%) 7 0/1269 (0%) 0 0/4 (0%) 0
    Carpal tunnel syndrome 7/8420 (0.1%) 7 0/1269 (0%) 0 0/4 (0%) 0
    Central nervous system lesion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cerebellar haemorrhage 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cerebellar infarction 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Cerebral arteriosclerosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cerebral artery embolism 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Cerebral atrophy 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Cerebral cyst 3/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Cerebral disorder 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Cerebral haemorrhage 9/8420 (0.1%) 9 0/1269 (0%) 0 0/4 (0%) 0
    Cerebral infarction 15/8420 (0.2%) 17 3/1269 (0.2%) 3 0/4 (0%) 0
    Cerebral thrombosis 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Cerebrovascular accident 63/8420 (0.7%) 73 16/1269 (1.3%) 16 0/4 (0%) 0
    Cerebrovascular disorder 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Cognitive disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Coma 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Coma hepatic 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Convulsion 22/8420 (0.3%) 25 8/1269 (0.6%) 8 0/4 (0%) 0
    Dementia 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Depressed level of consciousness 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Dizziness 13/8420 (0.2%) 14 5/1269 (0.4%) 5 0/4 (0%) 0
    Dysarthria 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Dyskinesia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Embolic stroke 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Encephalitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Encephalopathy 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Epilepsy 12/8420 (0.1%) 13 2/1269 (0.2%) 2 0/4 (0%) 0
    Facial paresis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Grand mal convulsion 8/8420 (0.1%) 8 0/1269 (0%) 0 0/4 (0%) 0
    Guillain-barre syndrome 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Haemorrhage intracranial 5/8420 (0.1%) 5 3/1269 (0.2%) 3 0/4 (0%) 0
    Haemorrhagic cerebral infarction 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Haemorrhagic stroke 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Headache 22/8420 (0.3%) 26 2/1269 (0.2%) 3 0/4 (0%) 0
    Hemianopia 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Hemianopia heteronymous 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Hemiparesis 9/8420 (0.1%) 9 1/1269 (0.1%) 1 0/4 (0%) 0
    Hepatic encephalopathy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hydrocephalus 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Hypoaesthesia 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Hypoglycaemic coma 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypoxic-ischaemic encephalopathy 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Intracranial hypotension 4/8420 (0%) 4 1/1269 (0.1%) 1 0/4 (0%) 0
    Intracranial pressure increased 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ischaemic cerebral infarction 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Ischaemic stroke 5/8420 (0.1%) 5 3/1269 (0.2%) 3 0/4 (0%) 0
    Ivth nerve paralysis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lacunar infarction 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Lethargy 5/8420 (0.1%) 5 3/1269 (0.2%) 3 0/4 (0%) 0
    Loss of consciousness 5/8420 (0.1%) 5 2/1269 (0.2%) 3 0/4 (0%) 0
    Lumbar radiculopathy 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Memory impairment 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Mental impairment 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Migraine 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Mononeuropathy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Moyamoya disease 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Multiple sclerosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Myoclonus 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Neuralgia 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Neurological symptom 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Neuropathy peripheral 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Normal pressure hydrocephalus 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Optic neuritis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Paraesthesia 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Parkinsonism 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Partial seizures 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Peroneal nerve palsy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pneumocephalus 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Presyncope 4/8420 (0%) 4 2/1269 (0.2%) 2 0/4 (0%) 0
    Quadriplegia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Radiculopathy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Sciatica 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Sedation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Somnolence 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Speech disorder 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Spinal cord compression 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Spinal cord oedema 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Subarachnoid haemorrhage 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Subdural hygroma 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Syncope 33/8420 (0.4%) 36 16/1269 (1.3%) 16 0/4 (0%) 0
    Tension headache 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Toxic encephalopathy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Transient ischaemic attack 30/8420 (0.4%) 34 4/1269 (0.3%) 4 0/4 (0%) 0
    Tremor 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Trigeminal neuralgia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Unresponsive to stimuli 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Vascular encephalopathy 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Viith nerve paralysis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Visual field defect 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Visual pathway disorder 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Vith nerve paralysis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    Abnormal labour 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Abortion spontaneous 2/4025 (0%) 2 0/524 (0%) 0 0/2 (0%) 0
    Delivery 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Pre-eclampsia 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Pregnancy 7/4025 (0.2%) 7 0/524 (0%) 0 0/2 (0%) 0
    Premature labour 2/4025 (0%) 2 0/524 (0%) 0 0/2 (0%) 0
    Psychiatric disorders
    Abnormal behaviour 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Aggression 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Alcohol abuse 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Alcohol withdrawal syndrome 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Anxiety 6/8420 (0.1%) 6 0/1269 (0%) 0 0/4 (0%) 0
    Anxiety disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bipolar disorder 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Completed suicide 8/8420 (0.1%) 8 0/1269 (0%) 0 0/4 (0%) 0
    Confusional state 14/8420 (0.2%) 16 2/1269 (0.2%) 2 0/4 (0%) 0
    Delirium 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Delusion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Depression 17/8420 (0.2%) 18 3/1269 (0.2%) 5 0/4 (0%) 0
    Depression suicidal 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Disorientation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Drug abuse 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Drug dependence 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Drug dependence, postpartum 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Hallucination, visual 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Major depression 2/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Mania 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Mental disorder 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Mental status changes 13/8420 (0.2%) 13 7/1269 (0.6%) 7 0/4 (0%) 0
    Panic disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Paranoia 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Post-traumatic stress disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Psychotic disorder 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Substance abuse 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Substance-induced psychotic disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Suicidal ideation 6/8420 (0.1%) 6 0/1269 (0%) 0 0/4 (0%) 0
    Suicide attempt 8/8420 (0.1%) 9 0/1269 (0%) 0 0/4 (0%) 0
    Renal and urinary disorders
    Bladder disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bladder neck obstruction 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bladder obstruction 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Calculus ureteric 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Calculus urinary 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Crush syndrome 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Dysuria 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Glomerulonephritis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Glomerulonephritis membranoproliferative 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Haematuria 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Haemorrhage urinary tract 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hydronephrosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hydroureter 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Micturition disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Nephrolithiasis 9/8420 (0.1%) 10 2/1269 (0.2%) 2 0/4 (0%) 0
    Nephropathy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Proteinuria 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Renal artery stenosis 2/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Renal failure 12/8420 (0.1%) 13 2/1269 (0.2%) 2 0/4 (0%) 0
    Renal failure acute 10/8420 (0.1%) 11 6/1269 (0.5%) 9 0/4 (0%) 0
    Renal failure chronic 5/8420 (0.1%) 5 2/1269 (0.2%) 2 0/4 (0%) 0
    Renal mass 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Renal tubular necrosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Stress urinary incontinence 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Urethral stenosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Urinary incontinence 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Urinary retention 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Urinary tract obstruction 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Vesical fistula 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Reproductive system and breast disorders
    Adnexa uteri cyst 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Adnexa uteri mass 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Artificial menopause 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Benign prostatic hyperplasia 8/4394 (0.2%) 8 2/745 (0.3%) 2 0/2 (0%) 0
    Breast enlargement 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Breast pain 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cystocele 2/4025 (0%) 2 0/524 (0%) 0 0/2 (0%) 0
    Endometrial disorder 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Endometrial hyperplasia 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Endometriosis 2/4025 (0%) 2 0/524 (0%) 0 0/2 (0%) 0
    Gynaecomastia 1/4394 (0%) 1 0/745 (0%) 0 0/2 (0%) 0
    Menometrorrhagia 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Menopausal disorder 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Menorrhagia 2/4025 (0%) 2 0/524 (0%) 0 0/2 (0%) 0
    Metrorrhagia 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Ovarian cyst 8/4025 (0.2%) 9 1/524 (0.2%) 1 0/2 (0%) 0
    Ovarian cyst ruptured 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Ovarian mass 2/4025 (0%) 2 0/524 (0%) 0 0/2 (0%) 0
    Postmenopausal haemorrhage 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Prostatic obstruction 1/4394 (0%) 2 0/745 (0%) 0 0/2 (0%) 0
    Prostatism 1/4394 (0%) 1 0/745 (0%) 0 0/2 (0%) 0
    Prostatitis 2/4394 (0%) 2 0/745 (0%) 0 0/2 (0%) 0
    Prostatomegaly 1/4394 (0%) 1 0/745 (0%) 0 0/2 (0%) 0
    Rectocele 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Testicular atrophy 1/4394 (0%) 1 0/745 (0%) 0 0/2 (0%) 0
    Uterine polyp 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Uterine prolapse 3/4025 (0.1%) 3 0/524 (0%) 0 0/2 (0%) 0
    Vaginal haemorrhage 2/4025 (0%) 2 0/524 (0%) 0 0/2 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Acute respiratory failure 2/8420 (0%) 2 2/1269 (0.2%) 2 0/4 (0%) 0
    Aspiration 0/8420 (0%) 0 2/1269 (0.2%) 2 0/4 (0%) 0
    Asthma 11/8420 (0.1%) 12 3/1269 (0.2%) 5 0/4 (0%) 0
    Atelectasis 2/8420 (0%) 2 2/1269 (0.2%) 2 0/4 (0%) 0
    Bronchial secretion retention 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Bronchiectasis 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Bronchitis chronic 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Broncholithiasis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Chronic obstructive pulmonary disease 9/8420 (0.1%) 11 3/1269 (0.2%) 5 0/4 (0%) 0
    Cough 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Dyspnoea 19/8420 (0.2%) 19 4/1269 (0.3%) 4 0/4 (0%) 0
    Dyspnoea at rest 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Dyspnoea exertional 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Epistaxis 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Haemothorax 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypoxia 5/8420 (0.1%) 5 2/1269 (0.2%) 2 0/4 (0%) 0
    Idiopathic pulmonary fibrosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Interstitial lung disease 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lung disorder 7/8420 (0.1%) 7 0/1269 (0%) 0 0/4 (0%) 0
    Lung infiltration 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Nasal congestion 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Nasal septum deviation 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Neonatal hypoxia 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Orthopnoea 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Paranasal cyst 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Pleural effusion 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Pleurisy 1/8420 (0%) 1 2/1269 (0.2%) 2 0/4 (0%) 0
    Pleuritic pain 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Pneumonia aspiration 7/8420 (0.1%) 8 4/1269 (0.3%) 4 0/4 (0%) 0
    Pneumonitis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Pneumothorax 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Productive cough 0/8420 (0%) 0 2/1269 (0.2%) 2 0/4 (0%) 0
    Pulmonary embolism 23/8420 (0.3%) 23 3/1269 (0.2%) 3 0/4 (0%) 0
    Pulmonary fibrosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pulmonary hypertension 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Pulmonary infarction 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pulmonary mass 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Pulmonary oedema 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Pulmonary sarcoidosis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Pulmonary thrombosis 1/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Respiratory arrest 7/8420 (0.1%) 7 1/1269 (0.1%) 1 0/4 (0%) 0
    Respiratory distress 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Respiratory failure 8/8420 (0.1%) 8 6/1269 (0.5%) 6 0/4 (0%) 0
    Sleep apnoea syndrome 8/8420 (0.1%) 9 0/1269 (0%) 0 0/4 (0%) 0
    Skin and subcutaneous tissue disorders
    Dermatitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Diabetic foot 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hyperhidrosis 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Pemphigoid 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Rash 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Scar 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Skin lesion 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Skin ulcer 0/8420 (0%) 0 3/1269 (0.2%) 3 0/4 (0%) 0
    Swelling face 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Urticaria 2/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Social circumstances
    Alcohol use 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Surgical and medical procedures
    Abdominal hernia repair 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Abdominal panniculectomy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Abortion induced 2/4025 (0%) 2 0/524 (0%) 0 0/2 (0%) 0
    Adhesiolysis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Adrenalectomy 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Aneurysm repair 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Aortic valve replacement 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Appendicectomy 7/8420 (0.1%) 7 0/1269 (0%) 0 0/4 (0%) 0
    Arterial bypass operation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Arteriovenous fistula operation 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Bladder operation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Brain operation 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Breast lump removal 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Bunion operation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cardiac ablation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cardiac pacemaker insertion 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Cardioversion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Carotid artery bypass 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Carotid endarterectomy 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Carpal tunnel decompression 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cataract operation 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Central venous catheterisation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Cholecystectomy 8/8420 (0.1%) 8 0/1269 (0%) 0 0/4 (0%) 0
    Cholelithotomy 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Colectomy 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Colostomy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Coronary angioplasty 1/8420 (0%) 1 1/1269 (0.1%) 2 0/4 (0%) 0
    Coronary arterial stent insertion 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Coronary artery bypass 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Craniotomy 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Enterostomy closure 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ethmoid sinus surgery 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Explorative laparotomy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Foot operation 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Foraminotomy 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Gallbladder operation 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Gastrectomy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Gastric bypass 3/8420 (0%) 3 1/1269 (0.1%) 1 0/4 (0%) 0
    Haematoma evacuation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Haemodialysis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Hernia hiatus repair 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    High frequency ablation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hip arthroplasty 11/8420 (0.1%) 12 1/1269 (0.1%) 2 0/4 (0%) 0
    Hip surgery 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypophysectomy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hysterectomy 6/4025 (0.1%) 6 0/524 (0%) 0 0/2 (0%) 0
    Ileostomy closure 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Implantable defibrillator insertion 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Implantable defibrillator replacement 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Incisional drainage 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Incisional hernia repair 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Internal fixation of fracture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Intervertebral disc operation 2/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Intestinal resection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Knee arthroplasty 5/8420 (0.1%) 6 1/1269 (0.1%) 1 0/4 (0%) 0
    Knee operation 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Leg amputation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lipoma excision 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lithotripsy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Liver transplant 0/8420 (0%) 0 2/1269 (0.2%) 2 0/4 (0%) 0
    Lung transplant 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Malignant breast lump removal 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Mastectomy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Mechanical ventilation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Medical device implantation 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Meningeal repair 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Meningioma surgery 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Meniscus operation 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Meniscus removal 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Nasal polypectomy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Nephrectomy 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Open reduction of fracture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Osteosynthesis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Ovarian cystectomy 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Pancreatectomy 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Parathyroidectomy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Peripheral nerve decompression 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Pituitary gland radiotherapy 5/8420 (0.1%) 5 0/1269 (0%) 0 0/4 (0%) 0
    Pituitary tumour removal 19/8420 (0.2%) 23 3/1269 (0.2%) 3 0/4 (0%) 0
    Plastic surgery to the face 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Preoperative care 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Prostatic operation 2/4394 (0%) 2 0/745 (0%) 0 0/2 (0%) 0
    Radiotherapy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Rectal prolapse repair 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Renal tumour excision 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Rotator cuff repair 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Salivary gland operation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Salpingo-oophorectomy bilateral 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Shoulder arthroplasty 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Sigmoidectomy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Sinus antrostomy 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Sinus operation 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Skin graft 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Skin neoplasm excision 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Sphenoid sinus operation 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Spinal decompression 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Spinal fusion surgery 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Spinal laminectomy 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Spinal operation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Splenectomy 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Stent placement 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Subdural haematoma evacuation 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Surgery 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Thyroid operation 1/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Thyroidectomy 2/8420 (0%) 2 1/1269 (0.1%) 1 0/4 (0%) 0
    Toe operation 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Transfusion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Transurethral prostatectomy 4/4394 (0.1%) 4 0/745 (0%) 0 0/2 (0%) 0
    Tumour excision 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Umbilical hernia repair 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Urethral repair 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Uterine dilation and curettage 1/4025 (0%) 1 0/524 (0%) 0 0/2 (0%) 0
    Wound closure 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Wound treatment 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Vascular disorders
    Aneurysm 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Aortic aneurysm 5/8420 (0.1%) 5 1/1269 (0.1%) 1 0/4 (0%) 0
    Aortic aneurysm rupture 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Aortic dissection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Aortic occlusion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Aortic stenosis 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Arterial occlusive disease 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Arteriosclerosis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Artery dissection 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Circulatory collapse 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Deep vein thrombosis 21/8420 (0.2%) 22 3/1269 (0.2%) 3 0/4 (0%) 0
    Haematoma 3/8420 (0%) 3 0/1269 (0%) 0 0/4 (0%) 0
    Haemorrhage 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Hypertension 7/8420 (0.1%) 7 4/1269 (0.3%) 5 0/4 (0%) 0
    Hypertensive emergency 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Hypotension 19/8420 (0.2%) 20 8/1269 (0.6%) 10 0/4 (0%) 0
    Iliac artery occlusion 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Infarction 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Lymphoedema 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Orthostatic hypertension 1/8420 (0%) 1 1/1269 (0.1%) 1 0/4 (0%) 0
    Orthostatic hypotension 5/8420 (0.1%) 7 2/1269 (0.2%) 2 0/4 (0%) 0
    Peripheral arterial occlusive disease 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Peripheral artery aneurysm 2/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Peripheral artery thrombosis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Peripheral embolism 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Phlebitis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Shock 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Shock haemorrhagic 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Superior vena cava syndrome 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Temporal arteritis 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Thrombophlebitis 4/8420 (0%) 4 0/1269 (0%) 0 0/4 (0%) 0
    Thrombosis 2/8420 (0%) 2 0/1269 (0%) 0 0/4 (0%) 0
    Vein disorder 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Venous insufficiency 0/8420 (0%) 0 1/1269 (0.1%) 1 0/4 (0%) 0
    Venous thrombosis limb 1/8420 (0%) 1 0/1269 (0%) 0 0/4 (0%) 0
    Other (Not Including Serious) Adverse Events
    Somatropin Treated Untreated
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4912/8420 (58.3%) 591/1269 (46.6%) 0/4 (0%)
    Gastrointestinal disorders
    Diarrhoea 165/8420 (2%) 202 34/1269 (2.7%) 41 0/4 (0%) 0
    Gastrooesophageal reflux disease 167/8420 (2%) 169 26/1269 (2%) 26 0/4 (0%) 0
    Nausea 213/8420 (2.5%) 242 24/1269 (1.9%) 29 0/4 (0%) 0
    General disorders
    Asthenia 206/8420 (2.4%) 216 36/1269 (2.8%) 42 0/4 (0%) 0
    Fatigue 495/8420 (5.9%) 524 75/1269 (5.9%) 76 0/4 (0%) 0
    Oedema peripheral 546/8420 (6.5%) 624 27/1269 (2.1%) 31 0/4 (0%) 0
    Infections and infestations
    Influenza 198/8420 (2.4%) 216 13/1269 (1%) 14 0/4 (0%) 0
    Nasopharyngitis 176/8420 (2.1%) 211 16/1269 (1.3%) 16 0/4 (0%) 0
    Sinusitis 242/8420 (2.9%) 322 22/1269 (1.7%) 24 0/4 (0%) 0
    Upper respiratory tract infection 185/8420 (2.2%) 234 28/1269 (2.2%) 34 0/4 (0%) 0
    Investigations
    Weight increased 185/8420 (2.2%) 192 21/1269 (1.7%) 21 0/4 (0%) 0
    Metabolism and nutrition disorders
    Diabetes mellitus 194/8420 (2.3%) 209 24/1269 (1.9%) 24 0/4 (0%) 0
    Hyperlipidaemia 263/8420 (3.1%) 268 37/1269 (2.9%) 37 0/4 (0%) 0
    Vitamin d deficiency 144/8420 (1.7%) 145 39/1269 (3.1%) 39 0/4 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 742/8420 (8.8%) 887 48/1269 (3.8%) 54 0/4 (0%) 0
    Back pain 347/8420 (4.1%) 384 33/1269 (2.6%) 35 0/4 (0%) 0
    Myalgia 236/8420 (2.8%) 252 12/1269 (0.9%) 12 0/4 (0%) 0
    Osteopenia 184/8420 (2.2%) 185 35/1269 (2.8%) 35 0/4 (0%) 0
    Osteoporosis 164/8420 (1.9%) 165 41/1269 (3.2%) 41 0/4 (0%) 0
    Pain in extremity 276/8420 (3.3%) 315 30/1269 (2.4%) 38 0/4 (0%) 0
    Nervous system disorders
    Carpal tunnel syndrome 181/8420 (2.1%) 196 10/1269 (0.8%) 11 0/4 (0%) 0
    Dizziness 220/8420 (2.6%) 238 40/1269 (3.2%) 44 0/4 (0%) 0
    Headache 533/8420 (6.3%) 607 57/1269 (4.5%) 66 0/4 (0%) 0
    Paraesthesia 210/8420 (2.5%) 233 4/1269 (0.3%) 4 0/4 (0%) 0
    Psychiatric disorders
    Depression 557/8420 (6.6%) 590 54/1269 (4.3%) 56 0/4 (0%) 0
    Insomnia 185/8420 (2.2%) 192 22/1269 (1.7%) 22 0/4 (0%) 0
    Reproductive system and breast disorders
    Erectile dysfunction 74/4394 (1.7%) 76 16/745 (2.1%) 16 0/2 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Sleep apnoea syndrome 182/8420 (2.2%) 184 20/1269 (1.6%) 20 0/4 (0%) 0
    Vascular disorders
    Hypertension 630/8420 (7.5%) 671 59/1269 (4.6%) 61 0/4 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01088399
    Other Study ID Numbers:
    • 6448
    • B9R-MC-GDGA
    First Posted:
    Mar 17, 2010
    Last Update Posted:
    Apr 21, 2014
    Last Verified:
    Mar 1, 2014